The role of microglia in retinal neurodegeneration: Alzheimer's disease, Parkinson, and glaucoma

Frontiers in Aging Neuroscience

Volumn 9, Issue JUL, 2017, Pages

  Ramirez, Ana I ^a   de Hoz, Rosa ^a   Salobrar Garcia, Elena ^a   Salazar, Juan J ^a   Rojas, Blanca ^a   Ajoy, Daniel ^a   López Cuenca, Inés ^a   Rojas, Pilar ^a,b   Triviño, Alberto ^a   Ramírez, José M ^a  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN   (Spain)

Author keywords

Alzheimer's disease; Beta amyloid; Glaucoma; Microglia; Neuroinflammation; Parkinson; Retina; Synuclein

Indexed keywords

ALZHEIMER DISEASE; BLOOD RETINA BARRIER; CELL ACTIVATION; DOPAMINERGIC NERVE CELL; GLAUCOMA; HUMAN; MICROGLIA; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; OPTIC NERVE; PARKINSON DISEASE; PATHOGENESIS; RETINA; RETINAL THICKNESS; REVIEW; SUBSTANTIA NIGRA; VISUAL IMPAIRMENT;

EID: 85024393234     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2017.00214     Document Type: Review

References (295)

1. Alafuzoff, I., and Parkkinen, L. (2014). Staged pathology in Parkinson's disease. Parkinsonism Relat. Disord. 20 (Suppl. 1), S57-S61. doi: 10.1016/S1353-8020(13)70016-6
2. Alexandrov, P. N., Pogue, A., Bhattacharjee, S., and Lukiw, W. J. (2011). Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer's disease. Neuroreport 22, 623-627. doi: 10.1097/WNR.0b013e3283497334
3. Anderson, J. P., Walker, D. E., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., et al. (2006). Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281, 29739-29752. doi: 10.1074/jbc.M600933200
4. Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., et al. (2016). Targeting innate immunity for neurodegenerative disorders of the central nervous system. J. Neurochem. 138, 653-693. doi: 10.1111/jnc.13667
5. Antonucci, F., Turola, E., Riganti, L., Caleo, M., Gabrielli, M., Perrotta, C., et al. (2012). Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism. EMBO J. 31, 1231-1240. doi: 10.1038/emboj.2011.489
6. Appel, S. H., Beers, D. R., and Henkel, J. S. (2010). T cell-microglial dialogue in Parkinson's disease and amyotrophic lateral sclerosis: are we listening? Trends Immunol. 31, 7-17. doi: 10.1016/j.it.2009.09.003
7. Astafurov, K., Elhawy, E., Ren, L., Dong, C. Q., Igboin, C., Hyman, L., et al. (2014). Oral microbiome link to neurodegeneration in glaucoma. PLoS ONE 9:e104416. doi: 10.1371/journal.pone.0104416
8. Beach, T. G., Carew, J., Serrano, G., Adler, C. H., Shill, H. A., Sue, L. I., et al. (2014). Phosphorylated alpha-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects. Neurosci. Lett. 571, 34-38. doi: 10.1016/j.neulet.2014.04.027
9. Bennett, R. E., DeVos, S. L., Dujardin, S., Corjuc, B., Gor, R., Gonzalez, J., et al. (2017). Enhanced tau aggregation in the presence of Amyloid β. Am. J. Pathol. 187, 1601-1612. doi: 10.1016/j.ajpath.2017.03.011
10. Bialas, A. R., and Stevens, B. (2013). TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat. Neurosci. 16, 1773-1782. doi: 10.1038/nn.3560
11. Block, M. L., Zecca, L., and Hong, J. S. (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8, 57-69. doi: 10.1038/nrn2038
12. Bodis-Wollner, I. (1990). Visual deficits related to dopamine deficiency in experimental animals and Parkinson's disease patients. Trends Neurosci. 13, 296-302. doi: 10.1016/0166-2236(90)90113-O
13. Bodis-Wollner, I., Kozlowski, P. B., Glazman, S., and Miri, S. (2014). Alpha-Synuclein in the inner retina in Parkinson disease. Ann. Neurol. 75, 964-966. doi: 10.1002/ana.24182
14. Boeke, A., Rosen, D., Mastrianni, J., Xie, T., and Bernard, J. (2016). Optical coherence tomography as potential biomarker in Parkinson's disease and Alzheimer's disease (P5. 177). Neurology 86(16 Suppl.), P5. 177.
15. Bolos, M., Perea, J. R., and Avila, J. (2017). Alzheimer's disease as an inflammatory disease. Biomol. Concepts 8, 37-43. doi: 10.1515/bmc-2016-0029
16. Bosco, A., Breen, K. T., Anderson, S. R., Steele, M. R., Calkins, D. J., and Vetter, M. L. (2016). Glial coverage in the optic nerve expands in proportion to optic axon loss in chronic mouse glaucoma. Exp. Eye Res. 150, 34-43. doi: 10.1016/j.exer.2016.01.014
17. Bosco, A., Crish, S. D., Steele, M. R., Romero, C. O., Inman, D. M., Horner, P. J., et al. (2012). Early reduction of microglia activation by irradiation in a model of chronic glaucoma. PLoS ONE 7:e43602. doi: 10.1371/journal.pone.0043602
18. Bosco, A., Inman, D. M., Steele, M. R., Wu, G., Soto, I., Marsh-Armstrong, N., et al. (2008). Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. Invest. Ophthalmol. Vis. Sci. 49, 1437-1446. doi: 10.1167/iovs.07-1337
19. Bosco, A., Steele, M. R., and Vetter, M. L. (2011). Early microglia activation in a mouse model of chronic glaucoma. J. Comp. Neurol. 519, 599-620. doi: 10.1002/cne.22516
20. Braak, H., Del Tredici, K., Rub, U., de Vos, R. A., Jansen Steur, E. N., and Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol. Aging 24, 197-211. doi: 10.1016/S0197-4580(02)00065-9
21. Breen, K. T., Anderson, S. R., Steele, M. R., Calkins, D. J., Bosco, A., and Vetter, M. L. (2016). Loss of fractalkine signaling exacerbates axon transport dysfunction in a chronic model of glaucoma. Front. Neurosci. 10:526. doi: 10.3389/fnins.2016.00526
22. Broderick, C., Duncan, L., Taylor, N., and Dick, A. D. (2000). IFN-gamma and LPS-mediated IL-10-dependent suppression of retinal microglial activation. Invest. Ophthalmol. Vis. Sci. 41, 2613-2622.
23. Brown, G. C., and Neher, J. J. (2014). Microglial phagocytosis of live neurons. Nat. Rev. Neurosci. 15, 209-216. doi: 10.1038/nrn3710
24. Brown, G. C., and Vilalta, A. (2015). How microglia kill neurons. Brain Res. 1628(Pt B), 288-297. doi: 10.1016/j.brainres.2015.08.031
25. Burguillos, M. A., Deierborg, T., Kavanagh, E., Persson, A., Hajji, N., Garcia-Quintanilla, A., et al. (2011). Caspase signalling controls microglia activation and neurotoxicity. Nature 472, 319-324. doi: 10.1038/nature09788
26. Cagnin, A., Brooks, D. J., Kennedy, A. M., Gunn, R. N., Myers, R., Turkheimer, F. E., et al. (2001). In-vivo measurement of activated microglia in dementia. Lancet 358, 461-467. doi: 10.1016/S0140-6736(01)05625-2
27. Calabrese, V., Scapagnini, G., Giuffrida Stella, A. M., Bates, T. E., and Clark, J. B. (2001). Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem. Res. 26, 739-764. doi: 10.1023/A:1010955807739
28. Calsolaro, V., and Edison, P. (2016). Neuroinflammation in Alzheimer's disease: current evidence and future directions. Alzheimers Dement. 12, 719-732. doi: 10.1016/j.jalz.2016.02.010
29. Campello, L., Esteve-Rudd, J., Cuenca, N., and Martin-Nieto, J. (2013). The ubiquitin-proteasome system in retinal health and disease. Mol. Neurobiol. 47, 790-810. doi: 10.1007/s12035-012-8391-5
30. Cao, S., Standaert, D. G., and Harms, A. S. (2012). The gamma chain subunit of Fc receptors is required for alpha-synuclein-induced pro-inflammatory signaling in microglia. J. Neuroinflammat. 9, 259-2094-9-259. doi: 10.1186/1742-2094-9-259
31. Chang, R. C., Hudson, P., Wilson, B., Haddon, L., and Hong, J. S. (2000). Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia. Brain Res. 853, 236-244. doi: 10.1016/S0006-8993(99)02255-6
32. Chao, Y., Wong, S. C., and Tan, E. K. (2014). Evidence of inflammatory system involvement in Parkinson's disease. Biomed Res. Int. 2014:308654. doi: 10.1155/2014/308654
33. Chen, S. T., Hsu, J. R., Hsu, P. C., and Chuang, J. I. (2003). The retina as a novel in vivo model for studying the role of molecules of the Bcl-2 family in relation to MPTP neurotoxicity. Neurochem. Res. 28, 805-814. doi: 10.1023/A:1023298604347
34. Cherry, J. D., Olschowka, J. A., and O'Banion, M. K. (2014). Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J. Neuroinflammat. 11:98. doi: 10.1186/1742-2094-11-98
35. Chiarini, A., Armato, U., Liu, D., and Dal Pra, I. (2016). Calcium-sensing receptors of human neural cells play crucial roles in Alzheimer's disease. Front. Physiol. 7:134. doi: 10.3389/fphys.2016.00134
36. Chidlow, G., Ebneter, A., Wood, J. P., and Casson, R. J. (2016). Evidence supporting an association between expression of major histocompatibility complex II by microglia and optic nerve degeneration during experimental glaucoma. J. Glaucoma 25, 681-691. doi: 10.1097/IJG.0000000000000447
37. Cho, K. I., Searle, K., Webb, M., Yi, H., and Ferreira, P. A. (2012). Ranbp2 haploinsufficiency mediates distinct cellular and biochemical phenotypes in brain and retinal dopaminergic and glia cells elicited by the Parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell. Mol. Life Sci. 69, 3511-3527. doi: 10.1007/s00018-012-1071-9
38. Chrysostomou, V., Rezania, F., Trounce, I. A., and Crowston, J. G. (2013). Oxidative stress and mitochondrial dysfunction in glaucoma. Curr. Opin. Pharmacol. 13, 12-15. doi: 10.1016/j.coph.2012.09.008
39. Clark, A. K., Gruber-Schoffnegger, D., Drdla-Schutting, R., Gerhold, K. J., Malcangio, M., and Sandkuhler, J. (2015). Selective activation of microglia facilitates synaptic strength. J. Neurosci. 35, 4552-4570. doi: 10.1523/JNEUROSCI.2061-14.2015
40. Conway, K. A., Harper, J. D., and Lansbury, P. T. (1998). Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat. Med. 4, 1318-1320. doi: 10.1038/3311
41. Cosenza-Nashat, M., Zhao, M. L., Suh, H. S., Morgan, J., Natividad, R., Morgello, S., et al. (2009). Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathol. Appl. Neurobiol. 35, 306-328. doi: 10.1111/j.1365-2990.2008.01006.x
42. Cuenca, N., Fernández-Sánchez, L., Campello, L., Maneu, V., De la Villa, P., Lax, P., et al. (2014). Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases. Prog. Retin. Eye Res. 43, 17-75. doi: 10.1016/j.preteyeres.2014.07.001
43. Cuenca, N., Herrero, M. T., Angulo, A., de Juan, E., Martinez-Navarrete, G. C., Lopez, S., et al. (2005). Morphological impairments in retinal neurons of the scotopic visual pathway in a monkey model of Parkinson's disease. J. Comp. Neurol. 493, 261-273. doi: 10.1002/cne.20761
44. da Fonseca, A. C., Matias, D., Garcia, C., Amaral, R., Geraldo, L. H., Freitas, C., et al. (2014). The impact of microglial activation on blood-brain barrier in brain diseases. Front. Cell Neurosci. 8:362. doi: 10.3389/fncel.2014.00362
45. D'Andrea, M. R. (2005). Add Alzheimer's disease to the list of autoimmune diseases. Med. Hypotheses 64, 458-463. doi: 10.1016/j.mehy.2004.08.024
46. Danesh-Meyer, H. V., Birch, H., Ku, J. Y., Carroll, S., and Gamble, G. (2006). Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging. Neurology 67, 1852-1854. doi: 10.1212/01.wnl.0000244490.07925.8b
47. Dauer, W., and Przedborski, S. (2003). Parkinson's disease: mechanisms and models. Neuron 39, 889-909. doi: 10.1016/s0896-6273(03)00568-3
48. de Hoz, R., Gallego, B. I., Ramírez, A. I., Rojas, B., Salazar, J. J., Valiente-Soriano, F. J., et al. (2013). Rod-like microglia are restricted to eyes with laser-induced ocular hypertension but absent from the microglial changes in the contralateral untreated eye. PLoS ONE 8:e83733. doi: 10.1371/journal.pone.0083733
49. de Hoz, R., Rojas, B., Ramirez, A. I., Salazar, J. J., Gallego, B. I., Trivino, A., et al. (2016). Retinal Macroglial Responses in Health and Disease. Biomed. Res. Int. 2016:2954721. doi: 10.1155/2016/2954721
50. de Lau, L. M., and Breteler, M. M. (2006). Epidemiology of Parkinson's disease. Lancet Neurol 5, 525-535. doi: 10.1016/S1474-4422(06)70471-9
51. De Strooper, B., and Karran, E. (2016). The cellular phase of Alzheimer's disease. Cell 164, 603-615. doi: 10.1016/j.cell.2015.12.056
52. Deane, R., Singh, I., Sagare, A. P., Bell, R. D., Ross, N. T., LaRue, B., et al. (2012). A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Invest. 122, 1377-1392. doi: 10.1172/JCI58642
53. Ding, Y. M., Jaumotte, J. D., Signore, A. P., and Zigmond, M. J. (2004). Effects of 6-hydroxydopamine on primary cultures of substantia nigra: specific damage to dopamine neurons and the impact of glial cell line-derived neurotrophic factor. J. Neurochem. 89, 776-787. doi: 10.1111/j.1471-4159.2004.02415.x
54. Djamgoz, M. B., Hankins, M. W., Hirano, J., and Archer, S. N. (1997). Neurobiology of retinal dopamine in relation to degenerative states of the tissue. Vision Res. 37, 3509-3529. doi: 10.1016/S0042-6989(97)00129-6
55. Doorn, K. J., Moors, T., Drukarch, B., van de Berg, W. D., Lucassen, P. J., and van Dam, A. M. (2014). Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson's disease patients. Acta Neuropathol. Commun. 2:90-014-0090-1. doi: 10.1186/s40478-014-0090-1
56. Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., and Schmidt, M. H. (2016). Microglia-blood vessel interactions: a double-edged sword in brain pathologies. Acta Neuropathol. 131, 347-363. doi: 10.1007/s00401-015-1524-y
57. Ebneter, A., Casson, R. J., Wood, J. P., and Chidlow, G. (2010). Microglial activation in the visual pathway in experimental glaucoma: spatiotemporal characterization and correlation with axonal injury. Invest. Ophthalmol. Vis. Sci. 51, 6448-6460. doi: 10.1167/iovs.10-5284
58. Esteve-Rudd, J., Fernandez-Sanchez, L., Lax, P., De Juan, E., Martin-Nieto, J., and Cuenca, N. (2011). Rotenone induces degeneration of photoreceptors and impairs the dopaminergic system in the rat retina. Neurobiol. Dis. 44, 102-115. doi: 10.1016/j.nbd.2011.06.009
59. Fakhoury, M. (2016). Immune-mediated processes in neurodegeneration: where do we stand? J. Neurol. 263, 1683-1701. doi: 10.1007/s00415-016-8052-0
60. Fallon, M., Valero, O., Pazos, M., and Antón, A. (2017). Diagnostic accuracy of imaging devices in glaucoma: a meta-analysis. Surv. Ophthalmol. 62, 446-461. doi: 10.1016/j.survophthal.2017.01.001
61. Farina, C., Aloisi, F., and Meinl, E. (2007). Astrocytes are active players in cerebral innate immunity. Trends Immunol. 28, 138-145. doi: 10.1016/j.it.2007.01.005
62. Fellner, L., Irschick, R., Schanda, K., Reindl, M., Klimaschewski, L., Poewe, W., et al. (2013). Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia. Glia 61, 349-360. doi: 10.1002/glia.22437
63. Fu, R., Shen, Q., Xu, P., Luo, J. J., and Tang, Y. (2014). Phagocytosis of microglia in the central nervous system diseases. Mol. Neurobiol. 49, 1422-1434. doi: 10.1007/s12035-013-8620-6
64. Gallego, B. I., Salazar, J. J., de Hoz, R., Rojas, B., Ramírez, A. I., Salinas-Navarro, M., et al. (2012). IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice retina contralateral to experimental glaucoma. J. Neuroinflammat. 9:92. doi: 10.1186/1742-2094-9-92
65. Garcia-Martin, E. S., Rojas, B., Ramirez, A. I., de Hoz, R., Salazar, J. J., Yubero, R., et al. (2014). Macular thickness as a potential biomarker of mild Alzheimer's disease. Ophthalmology 121, 1149-1151.e3. doi: 10.1016/j.ophtha.2013.12.023
66. Garcia-Ospina, G. P., Jimenez-Del Rio, M., Lopera, F., and Velez-Pardo, C. (2003). Neuronal DNA damage correlates with a positive detection of c-Jun, nuclear factor kB, p53 and Par-4 transcription factors in Alzheimer's disease. Rev. Neurol 36, 1004-1010.
67. Garden, G. A., and Möller, T. (2006). Microglia biology in health and disease. J. Neuroimmune Pharmacol. 1, 127-137. doi: 10.1007/s11481-006-9015-5
68. Garlanda, C., Dinarello, C. A., and Mantovani, A. (2013). The interleukin-1 family: back to the future. Immunity 39, 1003-1018. doi: 10.1016/j.immuni.2013.11.010
69. Gasparini, L., Crowther, R. A., Martin, K. R., Berg, N., Coleman, M., Goedert, M., et al. (2011). Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: effects on axonal viability. Neurobiol. Aging 32, 419-433. doi: 10.1016/j.neurobiolaging.2009.03.002
70. Gazulla, J., and Cavero-Nagore, M. (2006). Glutamate and Alzheimer's disease. Rev. Neurol 42, 427-432.
71. George, S., and Brundin, P. (2015). Immunotherapy in Parkinson's disease: micromanaging Alpha-Synuclein aggregation. J. Parkinsons Dis. 5, 413-424. doi: 10.3233/JPD-150630
72. Ghiso, J. A., Doudevski, I., Ritch, R., and Rostagno, A. A. (2013). Alzheimer's disease and glaucoma: mechanistic similarities and differences. J. Glaucoma 22(Suppl. 5), S36-S38. doi: 10.1097/IJG.0b013e3182934af6
73. Giasson, B. I., Duda, J. E., Murray, I. V., Chen, Q., Souza, J. M., Hurtig, H. I., et al. (2000). Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290, 985-989. doi: 10.1126/science.290.5493.985
74. Giulian, D., and Ingeman, J. E. (1988). Colony-stimulating factors as promoters of ameboid microglia. J. Neurosci. 8, 4707-4717.
75. Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., and Gage, F. H. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918-934. doi: 10.1016/j.cell.2010.02.016
76. Glezer, I., Simard, A. R., and Rivest, S. (2007). Neuroprotective role of the innate immune system by microglia. Neuroscience 147, 867-883. doi: 10.1016/j.neuroscience.2007.02.055
77. Gold, M., and El Khoury, J. (2015). beta-amyloid, microglia, and the inflammasome in Alzheimer's disease. Semin. Immunopathol. 37, 607-611. doi: 10.1007/s00281-015-0518-0
78. Goldblum, D., Kipfer-Kauer, A., Sarra, G. M., Wolf, S., and Frueh, B. E. (2007). Distribution of amyloid precursor protein and amyloid-beta immunoreactivity in DBA/2J glaucomatous mouse retinas. Invest. Ophthalmol. Vis. Sci. 48, 5085-5090. doi: 10.1167/iovs.06-1249
79. Gonzalez, H., Contreras, F., and Pacheco, R. (2015). Regulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells. J. Neuroimmune Pharmacol. 10, 561-575. doi: 10.1007/s11481-015-9618-9
80. Gonzalez, H., Elgueta, D., Montoya, A., and Pacheco, R. (2014). Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J. Neuroimmunol. 274, 1-13. doi: 10.1016/j.jneuroim.2014.07.012
81. Gordon, R., Anantharam, V., Kanthasamy, A. G., and Kanthasamy, A. (2012). Proteolytic activation of proapoptotic kinase protein kinase Cdelta by tumor necrosis factor alpha death receptor signaling in dopaminergic neurons during neuroinflammation. J. Neuroinflammat. 9, 1-18. doi: 10.1186/1742-2094-9-82
82. Graeber, M. B., and Streit, W. J. (2010). Microglia: biology and pathology. Acta Neuropathol. 119, 89-105. doi: 10.1007/s00401-009-0622-0
83. Gramlich, O. W., Beck, S., von Hohenstein-Blaul, N., Boehm, N., Ziegler, A., Vetter, J. M., et al. (2013). Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina. PLoS ONE 8:e57557. doi: 10.1371/journal.pone.0057557
84. Grus, F. H., Joachim, S. C., Wuenschig, D., Rieck, J., and Pfeiffer, N. (2008). Autoimmunity and glaucoma. J. Glaucoma 17, 79-84. doi: 10.1097/IJG.0b013e318156a592
85. Guerriero, F., Sgarlata, C., Francis, M., Maurizi, N., Faragli, A., Perna, S., et al. (2016). Neuroinflammation, immune system and Alzheimer disease: searching for the missing link. Aging Clin. Exp. Res. doi: 10.1007/s40520-016-0637-z. [Epub ahead of print].
86. Guimaraes, J. S., Freire, M. A., Lima, R. R., Souza-Rodrigues, R. D., Costa, A. M., dos Santos, C. D., et al. (2009). Mechanisms of secondary degeneration in the central nervous system during acute neural disorders and white matter damage. Rev. Neurol. 48, 304-310.
87. Gupta, N., Ang, L. C., Noel de Tilly, L., Bidaisee, L., and Yucel, Y. H. (2006). Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Br. J. Ophthalmol. 90, 674-678. doi: 10.1136/bjo.2005.086769
88. Gupta, N., Fong, J., Ang, L. C., and Yucel, Y. H. (2008). Retinal tau pathology in human glaucomas. Can. J. Ophthalmol. 43, 53-60. doi: 10.3129/i07-185
89. Gupta, N., Ly, T., Zhang, Q., Kaufman, P. L., Weinreb, R. N., and Yucel, Y. H. (2007). Chronic ocular hypertension induces dendrite pathology in the lateral geniculate nucleus of the brain. Exp. Eye Res. 84, 176-184. doi: 10.1016/j.exer.2006.09.013
90. Hajee, M. E., March, W. F., Lazzaro, D. R., Wolintz, A. H., Shrier, E. M., Glazman, S., et al. (2009). Inner retinal layer thinning in Parkinson disease. Arch. Ophthalmol. 127, 737-741. doi: 10.1001/archophthalmol.2009.106
91. Hammam, T., Montgomery, D., Morris, D., and Imrie, F. (2008). Prevalence of serum autoantibodies and paraproteins in patients with glaucoma. Eye (Lond). 22, 349-353. doi: 10.1038/sj.eye.6702613
92. Hamza, T. H., Zabetian, C. P., Tenesa, A., Laederach, A., Montimurro, J., Yearout, D., et al. (2010). Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nat. Genet. 42, 781-785. doi: 10.1038/ng.642
93. Han, J., Wang, M., Ren, M., and Lou, H. (2017). Contributions of triggering-receptor-expressed-on-myeloid-cells-2 to neurological diseases. Int. J. Neurosci. 127, 368-375. doi: 10.1080/00207454.2016.1264072
94. Hanisch, U. K., and Kettenmann, H. (2007). Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387-1394. doi: 10.1038/nn1997
95. Hardy, J., and Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356. doi: 10.1126/science.1072994
96. Harms, A. S., Cao, S., Rowse, A. L., Thome, A. D., Li, X., Mangieri, L. R., et al. (2013). MHCII is required for alpha-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J. Neurosci. 33, 9592-9600. doi: 10.1523/JNEUROSCI.5610-12.2013
97. Hart, N. J., Koronyo, Y., Black, K. L., and Koronyo-Hamaoui, M. (2016). Ocular indicators of Alzheimer's: exploring disease in the retina. Acta Neuropathol. 132, 767-787. doi: 10.1007/s00401-016-1613-6
98. Hatfield, C. F., Herbert, J., van Someren, E. J., Hodges, J. R., and Hastings, M. H. (2004). Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer's dementia. Brain 127(Pt 5), 1061-1074. doi: 10.1093/brain/awh129
99. Hedges, T. R., III, Perez Galves, R., Speigelman, D., Barbas, N. R., Peli, E., et al. (1996). Retinal nerve fiber layer abnormalities in Alzheimer's disease. Acta Ophthalmol. Scand. 74, 271-275. doi: 10.1111/j.1600-0420.1996.tb00090.x
100. Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., et al. (2015). Neuroinflammation in Alzheimer's disease. Lancet Neurol. 14, 388-405. doi: 10.1016/S1474-4422(15)70016-5
101. Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., et al. (2013). NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493, 674-678. doi: 10.1038/nature11729
102. Hernández-Montiel, H. L. (2006). Aspectos moleculares y prospectos de terapias en la enfermedad de Parkinson. Bioquimia 31, 146-158.
103. Herrera, A. J., Espinosa-Oliva, A. M., Carrillo-Jimenez, A., Oliva-Martin, M. J., Garcia-Revilla, J., Garcia-Quintanilla, A., et al. (2015). Relevance of chronic stress and the two faces of microglia in Parkinson's disease. Front. Cell Neurosci. 9:312. doi: 10.3389/fncel.2015.00312
104. Holcomb, L., Gordon, M. N., McGowan, E., Yu, X., Benkovic, S., Jantzen, P., et al. (1998). Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat. Med. 4, 97-100. doi: 10.1038/nm0198-097
105. Hong, S., Dissing-Olesen, L., and Stevens, B. (2016). New insights on the role of microglia in synaptic pruning in health and disease. Curr. Opin. Neurobiol. 36, 128-134. doi: 10.1016/j.conb.2015.12.004
106. Hooghiemstra, A. M., Eggermont, L. H., Scheltens, P., van der Flier, W. M., and Scherder, E. J. (2015). The rest-activity rhythm and physical activity in early-onset dementia. Alzheimer Dis. Assoc. Disord 29, 45-49. doi: 10.1097/WAD.0000000000000037
107. Howell, G. R., Soto, I., Zhu, X., Ryan, M., Macalinao, D. G., Sousa, G. L., et al. (2012). Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma. J. Clin. Invest. 122, 1246-1261. doi: 10.1172/JCI61135
108. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., et al. (1996). Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274, 99-102.
109. Hsieh, C. L., Koike, M., Spusta, S. C., Niemi, E. C., Yenari, M., Nakamura, M. C., et al. (2009). A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J. Neurochem. 109, 1144-1156. doi: 10.1111/j.1471-4159.2009.06042.x
110. Inman, D. M., and Horner, P. J. (2007). Reactive nonproliferative gliosis predominates in a chronic mouse model of glaucoma. Glia 55, 942-953. doi: 10.1002/glia.20516
111. Inzelberg, R., Ramirez, J. A., Nisipeanu, P., and Ophir, A. (2004). Retinal nerve fiber layer thinning in Parkinson disease. Vision Res. 44, 2793-2797. doi: 10.1016/j.visres.2004.06.009
112. Iseri, P. K., Altinas, O., Tokay, T., and Yuksel, N. (2006). Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. J. Neuroophthalmol. 26, 18-24. doi: 10.1097/01.wno.0000204645.56873.26
113. Jack, C. S., Arbour, N., Manusow, J., Montgrain, V., Blain, M., McCrea, E., et al. (2005). TLR signaling tailors innate immune responses in human microglia and astrocytes. J. Immunol. 175, 4320-4330. doi: 10.4049/jimmunol.175.7.4320
114. Johnson, E. C., Jia, L., Cepurna, W. O., Doser, T. A., and Morrison, J. C. (2007). Global changes in optic nerve head gene expression after exposure to elevated intraocular pressure in a rat glaucoma model. Invest. Ophthalmol. Vis. Sci. 48, 3161-3177. doi: 10.1167/iovs.06-1282
115. Jones, E. V., and Bouvier, D. S. (2014). Astrocyte-secreted matricellular proteins in CNS remodelling during development and disease. Neural Plast. 2014:321209. doi: 10.1155/2014/321209
116. Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., et al. (2013). Variant of TREM2 associated with the risk of Alzheimer's disease. N. Engl. J. Med. 368, 107-116. doi: 10.1056/NEJMoa1211103
117. Kaarniranta, K., Salminen, A., Haapasalo, A., Soininen, H., and Hiltunen, M. (2011). Age-related macular degeneration (AMD): Alzheimer's disease in the eye? J. Alzheimer's Dis. 24, 615-631. doi: 10.3233/JAD-2011-101908
118. Kannarkat, G. T., Boss, J. M., and Tansey, M. G. (2013). The role of innate and adaptive immunity in Parkinson's disease. J. Parkinsons Dis. 3, 493-514. doi: 10.3233/JPD-130250
119. Karlstetter, M., Ebert, S., and Langmann, T. (2010). Microglia in the healthy and degenerating retina: Insights from novel mouse models. Immunobiology 215, 685-691. doi: 10.1016/j.imbio.2010.05.010
120. Karlstetter, M., Scholz, R., Rutar, M., Wong, W. T., Provis, J. M., and Langmann, T. (2015). Retinal microglia: just bystander or target for therapy? Prog. Retin. Eye Res. 45, 30-57. doi: 10.1016/j.preteyeres.2014.11.004
121. Kayabasi, U., Sergott, R. C., and Rispoli, M. (2014). Retinal examination for the diagnosis of Alzheimer's disease. Int. J. Ophthal. Pathol. 3:4. doi: 10.4172/2324-8599.1000145
122. Kesler, A., Vakhapova, V., Korczyn, A. D., Naftaliev, E., and Neudorfer, M. (2011). Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease. Clin. Neurol Neurosurg. 113, 523-526. doi: 10.1016/j.clineuro.2011.02.014
123. Kettenmann, H., Hanisch, U., Noda, M., and Verkhratsky, A. (2011). Physiology of Microglia. Physiol. Rev. 91, 461-553. doi: 10.1152/physrev.00011.2010
124. Kim, S. R., Chung, E. S., Bok, E., Baik, H. H., Chung, Y. C., Won, S. Y., et al. (2010). Prothrombin kringle-2 induces death of mesencephalic dopaminergic neurons in vivo and in vitro via microglial activation. J. Neurosci. Res. 88, 1537-1548. doi: 10.1002/jnr.22318
125. Kingsbury, A. E., Daniel, S. E., Sangha, H., Eisen, S., Lees, A. J., and Foster, O. J. (2004). Alteration in alpha-synuclein mRNA expression in Parkinson's disease. Mov. Disord. 19, 162-170. doi: 10.1002/mds.10683
126. Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., et al. (2007). UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446, 1091-1095. doi: 10.1038/nature05704
127. Komori, T., Morikawa, Y., Inada, T., Hisaoka, T., and Senba, E. (2011). Site-specific subtypes of macrophages recruited after peripheral nerve injury. Neuroreport 22, 911-917. doi: 10.1097/WNR.0b013e32834cd76a
128. Koronyo-Hamaoui, M., Koronyo, Y., Ljubimov, A. V., Miller, C. A., Ko, M. K., Black, K. L., et al. (2011). Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage 54(Suppl. 1), S204-S217. doi: 10.1016/j.neuroimage.2010.06.020
129. Krasodomska, K., Lubinski, W., Potemkowski, A., and Honczarenko, K. (2010). Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer's disease. Doc. Ophthalmol. 121, 111-121. doi: 10.1007/s10633-010-9238-x
130. Kreutzberg, G. (1995). Microglia, the first line of defence in brain pathologies. Arzneimittelforschung 45, 357-360.
131. Kreutzberg, G. W. (1996). Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19, 312-318. doi: 10.1016/0166-2236(96)10049-7
132. Kumar-Singh, S., Pirici, D., McGowan, E., Serneels, S., Ceuterick, C., Hardy, J., et al. (2005). Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls. Am. J. Pathol. 167, 527-543. doi: 10.1016/S0002-9440(10)62995-1
133. Kummer, M. P., Hermes, M., Delekarte, A., Hammerschmidt, T., Kumar, S., Terwel, D., et al. (2011). Nitration of tyrosine 10 critically enhances amyloid beta aggregation and plaque formation. Neuron 71, 833-844. doi: 10.1016/j.neuron.2011.07.001
134. La Morgia, C., Barboni, P., Rizzo, G., Carbonelli, M., Savini, G., Scaglione, C., et al. (2013). Loss of temporal retinal nerve fibers in Parkinson disease: a mitochondrial pattern? Eur. J. Neurol. 20, 198-201. doi: 10.1111/j.1468-1331.2012.03701.x
135. La Morgia, C., Ross-Cisneros, F. N., Hannibal, J., Montagna, P., Sadun, A. A., and Carelli, V. (2011). Melanopsin-expressing retinal ganglion cells: implications for human diseases. Vision Res. 51, 296-302. doi: 10.1016/j.visres.2010.07.023
136. Lakey-Beitia, J., González, Y., Doens, D., Stephens, D. E., Santamaría, R., Murillo, E., et al. (2017). Assessment of novel curcumin derivatives as potent inhibitors of inflammation and Amyloid-β aggregation in Alzheimer's disease. J. Alzheimer's Dis. doi: 10.3233/JAD-170071. [Epub ahead of print].
137. Langmann, T. (2007). Microglia activation in retinal degeneration. J. Leukoc. Biol. 81, 1345-1351. doi: 10.1189/jlb.0207114
138. Lascaratos, G., Garway-Heath, D. F., Willoughby, C. E., Chau, K., and Schapira, A. H. V. (2012). Mitochondrial dysfunction in glaucoma: understanding genetic influences. Mitochondrion 12, 202-212. doi: 10.1016/j.mito.2011.11.004
139. Lauro, C., Cipriani, R., Catalano, M., Trettel, F., Chece, G., Brusadin, V., et al. (2010). Adenosine A1 receptors and microglial cells mediate CX3CL1-induced protection of hippocampal neurons against Glu-induced death. Neuropsychopharmacology 35, 1550-1559. doi: 10.1038/npp.2010.26
140. Lauro, C., Di Angelantonio, S., Cipriani, R., Sobrero, F., Antonilli, L., Brusadin, V., et al. (2008). Activity of adenosine receptors type 1 Is required for CX3CL1-mediated neuroprotection and neuromodulation in hippocampal neurons. J. Immunol. 180, 7590-7596. doi: 10.4049/jimmunol.180.11.7590
141. Le, W., Wu, J., and Tang, Y. (2016). Protective microglia and their regulation in Parkinson's disease. Front. Mol. Neurosci. 9:89. doi: 10.3389/fnmol.2016.00089
142. Lee, J., Shin, J., Chun, M., and Oh, S. (2014). Morphological analyses on retinal glial responses to glaucomatous injury evoked by venous cauterization. Appl. Microsc. 44, 21-29. doi: 10.9729/AM.2014.44.1.21
143. Lee, S., Van Bergen, N. J., Kong, G. Y., Chrysostomou, V., Waugh, H. S., O'Neill, E. C., et al. (2011). Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies. Exp. Eye Res. 93, 204-212. doi: 10.1016/j.exer.2010.07.015
144. Leem, E., Jeong, K. H., Won, S. Y., Shin, W. H., and Kim, S. R. (2016). Prothrombin Kringle-2: a potential inflammatory pathogen in the parkinsonian dopaminergic system. Exp. Neurobiol. 25, 147-155. doi: 10.5607/en.2016.25.4.147
145. Leroy, K., Bretteville, A., Schindowski, K., Gilissen, E., Authelet, M., De Decker, R., et al. (2007). Early axonopathy preceding neurofibrillary tangles in mutant tau transgenic mice. Am. J. Pathol. 171, 976-992. doi: 10.2353/ajpath.2007.070345
146. Leung, C. K. (2016). Optical coherence tomography imaging for glaucoma - today and tomorrow. Asia Pac. J. Ophthalmol. (Phila) 5, 11-16. doi: 10.1097/APO.0000000000000179
147. Licht, T., and Keshet, E. (2015). The vascular niche in adult neurogenesis. Mech. Dev. 138(Pt 1), 56-62. doi: 10.1016/j.mod.2015.06.001
148. Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481-487. doi: 10.1038/nature21029
149. Lim, C. K., Fernández-Gomez, F. J., Braidy, N., Estrada, C., Costa, C., Costa, S., et al. (2017). Involvement of the kynurenine pathway in the pathogenesis of Parkinson's disease. Prog. Neurobiol. 155, 76-95. doi: 10.1016/j.pneurobio.2015.12.009
150. Lim, J. K., Li, Q. X., He, Z., Vingrys, A. J., Wong, V. H., Currier, N., et al. (2016). The eye as a biomarker for Alzheimer's disease. Front. Neurosci. 10:536. doi: 10.3389/fnins.2016.00536
151. Linnartz, B., Kopatz, J., Tenner, A. J., and Neumann, H. (2012). Sialic acid on the neuronal glycocalyx prevents complement C1 binding and complement receptor-3-mediated removal by microglia. J. Neurosci. 32, 946-952. doi: 10.1523/JNEUROSCI.3830-11.2012
152. Liu, B., Rasool, S., Yang, Z., Glabe, C. G., Schreiber, S. S., Ge, J., et al. (2009). Amyloid-peptide vaccinations reduce (beta)-amyloid plaques but exacerbate vascular deposition and inflammation in the retina of Alzheimer's transgenic mice. Am. J. Pathol. 175, 2099-2110. doi: 10.2353/ajpath.2009.090159
153. London, A., Itskovich, E., Benhar, I., Kalchenko, V., Mack, M., Jung, S., et al. (2011). Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med. 208, 23-39. doi: 10.1084/jem.20101202
154. Lukiw, W. J., Gordon, W. C., Rogaev, E. I., Thompson, H., and Bazan, N. G. (2001). Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogenesis. Neuroreport 12, 53-57. doi: 10.1097/00001756-200101220-00019
155. Lull, M. E., and Block, M. L. (2010). Microglial Activation and Chronic Neurodegeneration. Neurotherapeutics 7, 354-365. doi: 10.1016/j.nurt.2010.05.014
156. Luo, C., Chen, M., and Xu, H. (2011). Complement gene expression and regulation in mouse retina and retinal pigment epithelium/choroid. Mol. Vis. 17, 1588-1597.
157. Luo, X., Ding, J., and Chen, S. (2010). Microglia in the aging brain: relevance to neurodegeneration. Mol. Neurodegen. 5:12. doi: 10.1186/1750-1326-5-12
158. MacCormick, I. J., Czanner, G., and Faragher, B. (2015). Developing retinal biomarkers of neurological disease: an analytical perspective. Biomark Med. 9, 691-701. doi: 10.2217/bmm.15.17
159. Madeira, M. H., Boia, R., Santos, P. F., Ambrosio, A. F., and Santiago, A. R. (2015). Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases. Mediat. Inflamm. 2015:673090. doi: 10.1155/2015/673090
160. Madeira, M. H., Ortin-Martinez, A., Nadal-Nicolas, F., Ambrosio, A. F., Vidal-Sanz, M., Agudo-Barriuso, M., et al. (2016). Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma. Sci. Rep. 6:27532. doi: 10.1038/srep27532
161. Magni, P., Ruscica, M., Dozio, E., Rizzi, E., Beretta, G., and Maffei Facino, R. (2012). Parthenolide inhibits the LPS-induced secretion of IL-6 and TNF-alpha and NF-kappaB nuclear translocation in BV-2 microglia. Phytother Res. 26, 1405-1409. doi: 10.1002/ptr.3732
162. Maiti, P., and Dunbar, G. L. (2016). Rationale for curcumin therapy in Alzheimer's disease. ARC J. Neurosci. 1, 10-16. doi: 10.20431/2456-057X.0103002
163. Maldonado, R. S., Mettu, P., El-Dairi, M., and Bhatti, M. T. (2015). The application of optical coherence tomography in neurologic diseases. Neurol. Clin. Pract. 5, 460-469. doi: 10.1212/cpj.0000000000000187
164. Martínez-Lazcano, J. C., Boll-Woehrlen, M. C., Hernández-Melesio, M., Rubio-Osornio, M., Sánchez-Mendoza, M., and Ríos, C. (2010). Radicales libres y estrés oxidativo en las enfermedades neurodegenerativas. Mensaje Bioquim 34, 43-59.
165. Martinez-Navarrete, G. C., Martin-Nieto, J., Esteve-Rudd, J., Angulo, A., and Cuenca, N. (2007). Alpha synuclein gene expression profile in the retina of vertebrates. Mol. Vis. 13, 949-961.
166. Maruyama, I., Ohguro, H., and Ikeda, Y. (2000). Retinal ganglion cells recognized by serum autoantibody against ?-enolase found in glaucoma patients. Invest. Ophthalmol. Vis. Sci. 41, 1657-1665.
167. Mattson, M. P. (2000). Apoptosis in neurodegenerative disorders. Nat. Rev. Mol. Cell Biol. 1, 120-129. doi: 10.1038/35040009
168. Maurage, C. A., Ruchoux, M. M., de Vos, R., Surguchov, A., and Destee, A. (2003). Retinal involvement in dementia with Lewy bodies: a clue to hallucinations? Ann. Neurol. 54, 542-547. doi: 10.1002/ana.10730
169. McKinnon, S. J. (2003). Glaucoma: ocular Alzheimer's disease. Front. Biosci 8, s1140-s1156. doi: 10.2741/1172
170. McKinnon, S. J., Lehman, D. M., Kerrigan-Baumrind, L. A., Merges, C. A., Pease, M. E., Kerrigan, D. F., et al. (2002). Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension. Invest. Ophthalmol. Vis. Sci. 43, 1077-1087.
171. McLaughlin, P., Zhou, Y., Ma, T., Liu, J., Zhang, W., Hong, J. S., et al. (2006). Proteomic analysis of microglial contribution to mouse strain-dependent dopaminergic neurotoxicity. Glia 53, 567-582. doi: 10.1002/glia.20294
172. Menzies, F. M., Henriquez, F. L., Alexander, J., and Roberts, C. W. (2010). Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation. Clin. Exp. Immunol. 160, 369-379. doi: 10.1111/j.1365-2249.2009.04086.x
173. Meyer-Luehmann, M., and Prinz, M. (2015). Myeloid cells in Alzheimer's disease: culprits, victims or innocent bystanders? Trends Neurosci. 38, 659-668. doi: 10.1016/j.tins.2015.08.011
174. Michelucci, A., Heurtaux, T., Grandbarbe, L., Morga, E., and Heuschling, P. (2009). Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: effects of oligomeric and fibrillar amyloid-beta. J. Neuroimmunol. 210, 3-12. doi: 10.1016/j.jneuroim.2009.02.003
175. Mirzaei, N., Tang, S. P., Ashworth, S., Coello, C., Plisson, C., Passchier, J., et al. (2016). In vivo imaging of microglial activation by positron emission tomography with [(11)C]PBR28 in the 5XFAD model of Alzheimer's disease. Glia 64, 993-1006. doi: 10.1002/glia.22978
176. Mogi, M., Harada, M., Narabayashi, H., Inagaki, H., Minami, M., and Nagatsu, T. (1996). Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease. Neurosci. Lett. 211, 13-16. doi: 10.1016/0304-3940(96)12706-3
177. Mosharov, E. V., Staal, R. G., Bove, J., Prou, D., Hananiya, A., Markov, D., et al. (2006). Alpha-synuclein overexpression increases cytosolic catecholamine concentration. J. Neurosci. 26, 9304-9311. doi: 10.1523/JNEUROSCI.0519-06.2006
178. Mosher, K. I., and Wyss-Coray, T. (2014). Microglial dysfunction in brain aging and Alzheimer's disease. Biochem. Pharmacol. 88, 594-604. doi: 10.1016/j.bcp.2014.01.008
179. Nagel, F., Bahr, M., and Dietz, G. P. (2009). Tyrosine hydroxylase-positive amacrine interneurons in the mouse retina are resistant against the application of various parkinsonian toxins. Brain Res. Bull. 79, 303-309. doi: 10.1016/j.brainresbull.2009.04.010
180. Nagele, R. G., D'Andrea, M. R., Lee, H., Venkataraman, V., and Wang, H.-Y. (2003). Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res. 971, 197-209. doi: 10.1016/S0006-8993(03)02361-8
181. Nakazawa, T., Nakazawa, C., Matsubara, A., Noda, K., Hisatomi, T., She, H., et al. (2006). Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J. Neurosci. 26, 12633-12641. doi: 10.1523/JNEUROSCI.2801-06.2006
182. Naskar, R., Wissing, M., and Thanos, S. (2002). Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma. Invest. Ophthalmol. Vis. Sci. 43, 2962-2968.
183. Nelson, A. R., Sweeney, M. D., Sagare, A. P., and Zlokovic, B. V. (2016). Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. Biochim. Biophys. Acta 1862, 887-900. doi: 10.1016/j.bbadis.2015.12.016
184. Neufeld, A. H. (1999). Microglia in the optic nerve head and the region of parapapillary chorioretinal atrophy in glaucoma. Arch. Ophthalmol. 117, 1050-1056. doi: 10.1001/archopht.117.8.1050
185. Neufeld, A. H., Hernandez, M. R., and Gonzalez, M. (1997). Nitric oxide synthase in the human glaucomatous optic nerve head. Arch. Ophthalmol. 115, 497-503. doi: 10.1001/archopht.1997.01100150499009
186. Neystat, M., Lynch, T., Przedborski, S., Kholodilov, N., Rzhetskaya, M., and Burke, R. E. (1999). Alpha-synuclein expression in substantia nigra and cortex in Parkinson's disease. Mov. Disord. 14, 417-422. doi: 10.1002/1531-8257(199905)14:3<417::AID-MDS1005>3.0.CO;2-X
187. Nickells, R. W. (1999). Apoptosis of retinal ganglion cells in glaucoma: an update of the molecular pathways involved in cell death. Surv. Ophthalmol. 43(Suppl. 1), S151-S161. doi: 10.1016/S0039-6257(99)00029-6
188. Nigro, A., Colombo, F., Casella, G., Finardi, A., Verderio, C., and Furlan, R. (2016). Myeloid extracellular vesicles: messengers from the demented brain. Front. Immunol. 7:17. doi: 10.3389/fimmu.2016.00017
189. Ning, A., Cui, J., To, E., Ashe, K. H., and Matsubara, J. (2008). Amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease. Invest. Ophthalmol. Vis. Sci. 49, 5136-5143. doi: 10.1167/iovs.08-1849
190. Nowacka, B., Lubinski, W., Honczarenko, K., Potemkowski, A., and Safranow, K. (2014). Ophthalmological features of Parkinson disease. Med. Sci. Monit. 20, 2243-2249. doi: 10.12659/MSM.890861
191. Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., et al. (2006). Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J. Neurosci. 26, 10129-10140. doi: 10.1523/JNEUROSCI.1202-06.2006
192. Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., et al. (2003). Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39, 409-421. doi: 10.1016/s0896-6273(03)00434-3
193. Ohsawa, K., Irino, Y., Nakamura, Y., Akazawa, C., Inoue, K., and Kohsaka, S. (2007). Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis. Glia 55, 604-616. doi: 10.1002/glia.20489
194. Olanow, C. W., and Tatton, W. G. (1999). Etiology and pathogenesis of Parkinson's disease. Annu. Rev. Neurosci. 22, 123-144. doi: 10.1146/annurev.neuro.22.1.123
195. Orr, C. F., Rowe, D. B., and Halliday, G. M. (2002). An inflammatory review of Parkinson's disease. Prog. Neurobiol. 68, 325-340. doi: 10.1016/S0301-0082(02)00127-2
196. Owen, D. R., and Matthews, P. M. (2011). Imaging brain microglial activation using positron emission tomography and translocator protein-specific radioligands. Int. Rev. Neurobiol. 101, 19-39. doi: 10.1016/B978-0-12-387718-5.00002-X
197. Painter, M. M., Atagi, Y., Liu, C. C., Rademakers, R., Xu, H., Fryer, J. D., et al. (2015). TREM2 in CNS homeostasis and neurodegenerative disease. Mol. Neurodegener. 10:43-015-0040-9. doi: 10.1186/s13024-015-0040-9
198. Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., et al. (2011). Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456-1458. doi: 10.1126/science.1202529
199. Paquet, C., Boissonnot, M., Roger, F., Dighiero, P., Gil, R., and Hugon, J. (2007). Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer's disease. Neurosci. Lett. 420, 97-99. doi: 10.1016/j.neulet.2007.02.090
200. Park, S., and Ou, Y. (2013). "Neurodegeneration in Glaucoma and Alzheimer's disease," in Recent Advances in Ophthalmology Research, ed G. Dimitrova (New York, NY: Nova Science Publishers), 59.
201. Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R. III., Lafaille, J. J., et al. (2013). Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596-1609. doi: 10.1016/j.cell.2013.11.030
202. Parnell, M., Guo, L., Abdi, M., and Cordeiro, M. F. (2012). Ocular manifestations of Alzheimer's disease in animal models. Int. J. Alzheimers Dis. 2012:786494. doi: 10.1155/2012/786494
203. Parpura, V., Heneka, M. T., Montana, V., Oliet, S. H., Schousboe, A., Haydon, P. G., et al. (2012). Glial cells in (patho)physiology. J. Neurochem. 121, 4-27. doi: 10.1111/j.1471-4159.2012.07664.x
204. Pasqualetti, G., Brooks, D. J., and Edison, P. (2015). The role of neuroinflammation in dementias. Curr. Neurol Neurosci. Rep. 15:17-015-0531-7. doi: 10.1007/s11910-015-0531-7
205. Pérez, M. A., and Arancibia, S. R. (2007). Estrés oxidativo y neurodegeneración:¿ causa o consecuencia. Arch. Neurocienc. 12, 45-54.
206. Perez, S. E., Lumayag, S., Kovacs, B., Mufson, E. J., and Xu, S. (2009). Beta-amyloid deposition and functional impairment in the retina of the APPswe/PS1DeltaE9 transgenic mouse model of Alzheimer's disease. Invest. Ophthalmol. Vis. Sci. 50, 793-800. doi: 10.1167/iovs.08-2384
207. Philipson, O., Lord, A., Gumucio, A., O'Callaghan, P., Lannfelt, L., and Nilsson, L. N. (2010). Animal models of amyloid-beta-related pathologies in Alzheimer's disease. FEBS J. 277, 1389-1409. doi: 10.1111/j.1742-4658.2010.07564.x
208. Pihlaja, R., Koistinaho, J., Kauppinen, R., Sandholm, J., Tanila, H., and Koistinaho, M. (2011). Multiple cellular and molecular mechanisms are involved in human Abeta clearance by transplanted adult astrocytes. Glia 59, 1643-1657. doi: 10.1002/glia.21212
209. Pinazo-Duran, M. D., Zanon-Moreno, V., Garcia-Medina, J. J., and Gallego-Pinazo, R. (2013). Evaluation of presumptive biomarkers of oxidative stress, immune response and apoptosis in primary open-angle glaucoma. Curr. Opin. Pharmacol. 13, 98-107. doi: 10.1016/j.coph.2012.10.007
210. Qiu, T., Liu, Q., Chen, Y. X., Zhao, Y. F., and Li, Y. M. (2015). Aβ42 and Aβ40: similarities and differences. J. Pept. Sci. 21, 522-529. doi: 10.1002/psc.2789
211. Quigley, H. A., and Broman, A. T. (2006). The number of people with glaucoma worldwide in 2010 and 2020. Br. J. Ophthalmol. 90, 262-267. doi: 10.1136/bjo.2005.081224
212. Quigley, H. A., Dunkelberger, G. R., and Green, W. R. (1988). Chronic human glaucoma causing selectively greater loss of large optic nerve fibers. Ophthalmology 95, 357-363. doi: 10.1016/S0161-6420(88)33176-3
213. Ransohoff, R. M., and Cardona, A. E. (2010). The myeloid cells of the central nervous system parenchyma. Nature 468, 253-262. doi: 10.1038/nature09615
214. Ransohoff, R. M., and El Khoury, J. (2015). Microglia in health and disease. Cold Spring Harb. Perspect. Biol. 8:a020560. doi: 10.1101/cshperspect.a020560
215. Ratnayaka, J. A., Serpell, L. C., and Lotery, A. J. (2015). Dementia of the eye: the role of amyloid beta in retinal degeneration. Eye (Lond). 29, 1013-1026. doi: 10.1038/eye.2015.100
216. Ritzel, R. M., Patel, A. R., Pan, S., Crapser, J., Hammond, M., Jellison, E., et al. (2015). Age- and location-related changes in microglial function. Neurobiol. Aging 36, 2153-2163. doi: 10.1016/j.neurobiolaging.2015.02.016
217. Rogers, J. T., Morganti, J. M., Bachstetter, A. D., Hudson, C. E., Peters, M. M., Grimmig, B. A., et al. (2011). CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. J. Neurosci. 31, 16241-16250. doi: 10.1523/JNEUROSCI.3667-11.2011
218. Rojas, B., Gallego, B. I., Ramírez, A. I., Salazar, J. J., de Hoz, R., Valiente-Soriano, F. J., et al. (2014). Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers. J. Neuroinflammat. 11:133. doi: 10.1186/1742-2094-11-133
219. Salobrar-Garcia, E., Garcia, Y., Lostao, C., Jañez, L., de Hoz, R., Rojas, B., et al. (2016a). Maculopapillary analysis in the posterior pole in patients with mild Alzheimer's disease. Acta Ophthalmol. doi: 10.1111/j.1755-3768.2016.0372
220. Salobrar-Garcia, E., Hoyas, I., Leal, M., de Hoz, R., Rojas, B., Ramirez, A. I., et al. (2015). Analysis of retinal peripapillary segmentation in early Alzheimer's disease patients. Biomed. Res. Int. 2015:636548. doi: 10.1155/2015/636548
221. Salobrar-Garcia, E., Leal, M., Hoyas, I., Salazar, J. J., Ramirez, A. I., de Hoz, R., et al. (2016b). Early changes in mild Alzheimer's disease in the neuroretinal rim segmentation. Acta Ophthalmol. doi: 10.1111/j.1755-3768.2016.0449
222. Salobrar-García, E., Ramírez, A. I., de Hoz, R., Rojas, P., Salazar, J. J., Rojas, B., et al. (2016c). "cular manifestations of dementia: the eye and its role in the diagnosis and monitoring, Chapter 15" in Update on Dementia, ed D. Moretti (InTech). doi: 10.5772/64490
223. Satue, M., Rodrigo, M. J., Obis, J., Vilades, E., Gracia, H., Otin, S., et al. (2017). Evaluation of progressive visual dysfunction and retinal degeneration in patients with Parkinson's disease. Invest. Ophthalmol. Vis. Sci. 58, 1151-1157. doi: 10.1167/iovs.16-20460
224. Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., et al. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691-705. doi: 10.1016/j.neuron.2012.03.026
225. Schapansky, J., Nardozzi, J. D., and LaVoie, M. J. (2015). The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease. Neuroscience 302, 74-88. doi: 10.1016/j.neuroscience.2014.09.049
226. Schlamp, C. L., Li, Y., Dietz, J. A., Janssen, K. T., and Nickells, R. W. (2006). Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric. BMC Neurosci. 7:66. doi: 10.1186/1471-2202-7-66
227. Selkoe, D. J. (2004). Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nat. Cell Biol. 6, 1054-1061. doi: 10.1038/ncb1104-1054
228. Selkoe, D. J. (2008). Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav. Brain Res. 192, 106-113. doi: 10.1016/j.bbr.2008.02.016
229. Shareef, S., Sawada, A., and Neufeld, A. H. (1999). Isoforms of nitric oxide synthase in the optic nerves of rat eyes with chronic moderately elevated intraocular pressure. Invest. Ophthalmol. Vis. Sci. 40, 2884-2891.
230. Sharma, S., and Lipincott, W. (2017). Biomarkers in Alzheimer's disease-recent update. Curr. Alzheimer Res. doi: 10.2174/1567205014666170220141822. [Epub ahead of print].
231. Sheedy, F. J., Grebe, A., Rayner, K. J., Kalantari, P., Ramkhelawon, B., Carpenter, S. B., et al. (2013). CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat. Immunol. 14, 812-820. doi: 10.1038/ni.2639
232. Sheridan, G. K., and Murphy, K. J. (2013). Neuron-glia crosstalk in health and disease: fractalkine and CX3CR1 take centre stage. Open Biol. 3:130181. doi: 10.1098/rsob.130181
233. Simard, A. R., Soulet, D., Gowing, G., Julien, J. P., and Rivest, S. (2006). Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49, 489-502. doi: 10.1016/j.neuron.2006.01.022
234. Sofroniew, M., and Vinters, H. (2010). Astrocytes: biology and pathology. Acta Neuropathol. 119, 7-35. doi: 10.1007/s00401-009-0619-8
235. Solano, S. M., Miller, D. W., Augood, S. J., Young, A. B., and Penney, J. B. Jr. (2000). Expression of α-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: genes associated with familial Parkinson's disease. Ann. Neurol. 47, 201-210. doi: 10.1002/1531-8249(200002)47:2<201::AID-ANA10>3.0.CO;2-F
236. Southam, K. A., Vincent, A. J., and Small, D. H. (2016). Do Microglia default on network maintenance in Alzheimer's disease? J. Alzheimers Dis. 51, 657-669. doi: 10.3233/JAD-151075
237. Stasi, K., Nagel, D., Yang, X., Wang, R. F., Ren, L., Podos, S. M., et al. (2006). Complement component 1Q (C1Q) upregulation in retina of murine, primate, and human glaucomatous eyes. Invest. Ophthalmol. Vis. Sci. 47, 1024-1029. doi: 10.1167/iovs.05-0830
238. Steele, M. R., Inman, D. M., Sappington, R. R., Golestaneh, N., Marsh-Armstrong, N., Calkins, D., et al. (2005). Whole retinal microarray analysis of DBA/2J mice: a model for glaucoma. Invest. Ophthalmol. Vis. Sci. 46, 48. doi: 10.1167/iovs.05-0865
239. Stefanova, N., Klimaschewski, L., Poewe, W., Wenning, G. K., and Reindl, M. (2001). Glial cell death induced by overexpression of alpha-synuclein. J. Neurosci. Res. 65, 432-438. doi: 10.1002/jnr.1171
240. Stemplewitz, B., Keseru, M., Bittersohl, D., Buhmann, C., Skevas, C., Richard, G., et al. (2015). Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson's disease. Acta Ophthalmol. 93, e672-e677. doi: 10.1111/aos.12764
241. Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., et al. (2010). CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 11, 155-161. doi: 10.1038/ni.1836
242. Streit, W. J., Conde, J. R., Fendrick, S. E., Flanary, B. E., and Mariani, C. L. (2005). Role of microglia in the central nervous system's immune response. Neurol. Res. 27, 685-691. doi: 10.1179/016164105X49463
243. Streit, W. J., Mrak, R. E., and Griffin, W. S. (2004). Microglia and neuroinflammation: a pathological perspective. J. Neuroinflammat. 1:14. doi: 10.1186/1742-2094-1-14
244. Streit, W. J., Walter, S. A., and Pennell, N. A. (1999). Reactive microgliosis. Progr. Neurobiol. 57, 563-581. doi: 10.1016/S0301-0082(98)00069-0
245. Stutz, B., da Conceicao, F. S., Santos, L. E., Cadilhe, D. V., Fleming, R. L., Acquarone, M., et al. (2014). Murine dopaminergic Muller cells restore motor function in a model of Parkinson's disease. J. Neurochem. 128, 829-840. doi: 10.1111/jnc.12475
246. Suh, H.-S., Zhao, M.-L., Derico, L., Choi, N., and Lee, S. C. (2013). Insulin-like growth factor 1 and 2 (IGF1, IGF2) expression in human microglia: differential regulation by inflammatory mediators. J. Neuroinflammat. 10:805. doi: 10.1186/1742-2094-10-37
247. Surgucheva, I., McMahan, B., Ahmed, F., Tomarev, S., Wax, M. B., and Surguchov, A. (2002). Synucleins in glaucoma: implication of gamma-synuclein in glaucomatous alterations in the optic nerve. J. Neurosci. Res. 68, 97-106. doi: 10.1002/jnr.10198
248. Surguchov, A., McMahan, B., Masliah, E., and Surgucheva, I. (2001). Synucleins in ocular tissues. J. Neurosci. Res. 65, 68-77. doi: 10.1002/jnr.1129
249. Takeuchi, A., Irizarry, M. C., Duff, K., Saido, T. C., Hsiao Ashe, K., Hasegawa, M., et al. (2000). Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss. Am. J. Pathol. 157, 331-339. doi: 10.1016/S0002-9440(10)64544-0
250. Tang, Y., and Le, W. (2016). Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 53, 1181-1194. doi: 10.1007/s12035-014-9070-5
251. Tatton, W. G., Kwan, M. M., Verrier, M. C., Seniuk, N. A., and Theriault, E. (1990). MPTP produces reversible disappearance of tyrosine hydroxylase-containing retinal amacrine cells. Brain Res. 527, 21-31. doi: 10.1016/0006-8993(90)91056-M
252. Taylor, P. R., Martinez-Pomares, L., Stacey, M., Lin, H., Brown, G. D., and Gordon, S. (2005). Macrophage receptors and immune recognition. Annu. Rev. Immunol. 23, 901-944. doi: 10.1146/annurev.immunol.23.021704.115816
253. Taylor, S., Calder, C. J., Albon, J., Erichsen, J. T., Boulton, M. E., and Morgan, J. E. (2011). Involvement of the CD200 receptor complex in microglia activation in experimental glaucoma. Exp. Eye Res. 92, 338-343. doi: 10.1016/j.exer.2011.01.012
254. Terwel, D., Steffensen, K. R., Verghese, P. B., Kummer, M. P., Gustafsson, J. A., Holtzman, D. M., et al. (2011). Critical role of astroglial apolipoprotein E and liver X receptor-alpha expression for microglial Abeta phagocytosis. J. Neurosci. 31, 7049-7059. doi: 10.1523/JNEUROSCI.6546-10.2011
255. Tezel, G. (2009). the Fourth ARVO/Pfizer Ophthalmics Research Institute Conference,Working Group. The role of glia, mitochondria, and the immune system in glaucoma. Invest. Ophthalmol. Vis. Sci. 50, 1001-1012. doi: 10.1167/iovs.08-2717
256. Tezel, G. (2013). Immune regulation toward immunomodulation for neuroprotection in glaucoma. Curr. Opin. Pharmacol. 13, 23-31. doi: 10.1016/j.coph.2012.09.013
257. Tezel, G., Li, L. Y., Patil, R. V., and Wax, M. B. (2001). TNF-a and TNF-a receptor-1 in the retina of normal and glaucomatous eyes. Invest. Ophthalmol. Vis. Sci. 42, 1787-1794.
258. Tezel, G., Yang, J., and Wax, M. B. (2004). Heat shock proteins, immunity and glaucoma. Brain Res. Bull. 62, 473-480. doi: 10.1016/S0361-9230(03)00074-1
259. Tofaris, G. K., Razzaq, A., Ghetti, B., Lilley, K. S., and Spillantini, M. G. (2003). Ubiquitination of alpha-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function. J. Biol. Chem. 278, 44405-44411. doi: 10.1074/jbc.M308041200
260. Tsai, C. S., Ritch, R., Schwartz, B., Lee, S. S., Miller, N. R., Chi, T., et al. (1991). Optic nerve head and nerve fiber layer in Alzheimer's disease. Arch. Ophthalmol. 109, 199-204. doi: 10.1001/archopht.1991.01080020045040
261. Tsai, Y., Lu, B., Ljubimov, A. V., Girman, S., Ross-Cisneros, F. N., Sadun, A. A., et al. (2014). Ocular changes in TgF344-AD rat model of Alzheimer's disease. Invest. Ophthalmol. Vis. Sci. 55, 523-534. doi: 10.1167/iovs.13-12888
262. Udeochu, J. C., Shea, J. M., and Villeda, S. A. (2016). Microglia communication: parallels between aging and Alzheimer's disease. Clin. Exp. Neuroimmunol. 7, 114-125. doi: 10.1111/cen3.12307
263. Uttara, B., Singh, A. V., Zamboni, P., and Mahajan, R. T. (2009). Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol. 7, 65-74. doi: 10.2174/157015909787602823
264. van Boxel-Dezaire, A. H., Rani, M. R., and Stark, G. R. (2006). Complex modulation of cell type-specific signaling in response to type I interferons. Immunity 25, 361-372. doi: 10.1016/j.immuni.2006.08.014
265. Varnum, M. M., and Ikezu, T. (2012). The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain. Arch. Immunol. Ther. Exp. 60, 251-266. doi: 10.1007/s00005-012-0181-2
266. Veerhuis, R. (2011). Histological and direct evidence for the role of complement in the neuroinflammation of AD. Curr. Alzheimer Res. 8, 34-58. doi: 10.2174/156720511794604589
267. Verkhratsky, A., and Butt, A. M. (2013). Glial Physiology and Pathophysiology. Oxford: Wiley-Blackwell-John Wiley & Sons.
268. Verkhratsky, A., Parpura, V., Pekna, M., Pekny, M., and Sofroniew, M. (2014). Glia in the pathogenesis of neurodegenerative diseases. Biochem. Soc. Trans. 42, 1291-1301. doi: 10.1042/BST20140107
269. Vidal, L., Díaz, F., Villena, A., Moreno, M., Campos, J. G., and de Vargas, I. P. (2006). Nitric oxide synthase in retina and optic nerve head of rat with increased intraocular pressure and effect of timolol. Brain Res. Bull. 70, 406-413. doi: 10.1016/j.brainresbull.2006.07.009
270. Vivekanantham, S., Shah, S., Dewji, R., Dewji, A., Khatri, C., and Ologunde, R. (2015). Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair. Int. J. Neurosci. 125, 717-725. doi: 10.3109/00207454.2014.982795
271. Vodovotz, Y., Lucia, M. S., Flanders, K. C., Chesler, L., Xie, Q. W., Smith, T. W., et al. (1996). Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. J. Exp. Med. 184, 1425-1433. doi: 10.1084/jem.184.4.1425
272. Wang, K., Peng, B., and Lin, B. (2014). Fractalkine receptor regulates microglial neurotoxicity in an experimental mouse glaucoma model. Glia 62, 1943-1954 doi: 10.1002/glia.22715
273. Wang, J., Jackson, M. F., and Xie, Y. F. (2016). Glia and TRPM2 channels in plasticity of central nervous system and Alzheimer's diseases. Neural Plast. 2016:1680905. doi: 10.1155/2016/1680905
274. Wang, Q., Liu, Y., and Zhou, J. (2015). Neuroinflammation in Parkinson's disease and its potential as therapeutic target. Transl. Neurodegener. 4:19-015-0042-0. eCollection 2015. doi: 10.1186/s40035-015-0042-0
275. Wang, X. J., Zhang, S., Yan, Z. Q., Zhao, Y. X., Zhou, H. Y., Wang, Y., et al. (2011). Impaired CD200-CD200R-mediated microglia silencing enhances midbrain dopaminergic neurodegeneration: roles of aging, superoxide, NADPH oxidase, and p38 MAPK. Free Radic. Biol. Med. 50, 1094-1106. doi: 10.1016/j.freeradbiomed.2011.01.032
276. Wax, M. B., Tezel, G., and Edward, P. D. (1998). Clinical and ocular histopathological findings in a patient with normal-pressure glaucoma. Arch. Ophthalmol. 116, 993-1001. doi: 10.1001/archopht.116.8.993
277. Wax, M. B., Tezel, G., Kawase, K., and Kitazawa, Y. (2001). Serum autoantibodies to heat shock proteins in glaucoma patients from Japan and the United States. Ophthalmology 108, 296-302. doi: 10.1016/S0161-6420(00)00525-X
278. Williams, E. A., McGuone, D., Frosch, M. P., Hyman, B. T., Laver, N., and Stemmer-Rachamimov, A. (2017). Absence of Alzheimer disease neuropathologic changes in eyes of subjects with Alzheimer disease. J. Neuropathol. Exp. Neurol. 76, 376-383. doi: 10.1093/jnen/nlx020
279. Williams, P. A., Marsh-Armstrong, N., and Howell, G. R. (2017). Lasker/IRRF initiative on astrocytes and glaucomatous neurodegeneration participants. Neuroinflammation in glaucoma: a new opportunity. Exp. Eye Res. 157, 20-27. doi: 10.1016/j.exer.2017.02.014
280. Wostyn, P., Audenaert, K., and De Deyn, P. P. (2010). Alzheimer's disease: cerebral glaucoma? Med. Hypotheses 74, 973-977. doi: 10.1016/j.mehy.2009.12.019
281. Wu, L., Vadakkan, K. I., and Zhuo, M. (2007). ATP-induced chemotaxis of microglial processes requires P2Y receptor-activated initiation of outward potassium currents. Glia 55, 810-821. doi: 10.1002/glia.20500
282. Wyss-Coray, T. (2006). Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. Med. 12, 1005-1015. doi: 10.1038/nm1484
283. Xu, L., He, D., and Bai, Y. (2016). Microglia-mediated inflammation and neurodegenerative disease. Mol. Neurobiol. 53, 6709-6715. doi: 10.1007/s12035-015-9593-4
284. Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., et al. (1996). RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 382, 685-691.
285. Yan, Z., Gibson, S. A., Buckley, J. A., Qin, H., and Benveniste, E. N. (2016). Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clin. Immunol. doi: 10.1016/j.clim.2016.09.014. [Epub ahead of print].
286. Yang, J., Patil, R. V., Yu, H., Gordon, M., and Wax, M. B. (2001a). T cell subsets and sIL-2R/IL-2 levels in patients with glaucoma. Am. J. Ophthalmol. 131, 421-426. doi: 10.1016/S0002-9394(00)00862-X
287. Yang, J., Yang, P., Tezel, G., Patil, R. V., Hernandez, M. R., and Wax, M. B. (2001b). Induction of HLA-DR expression in human lamina cribrosa astrocytes by cytokines and simulated ischemia. Invest. Ophthalmol. Vis. Sci. 42, 365-371.
288. Yu, J. G., Feng, Y. F., Xiang, Y., Huang, J. H., Savini, G., Parisi, V., et al. (2014). Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis. PLoS ONE 9:e85718. doi: 10.1371/journal.pone.0085718
289. Yuan, L., and Neufeld, A. H. (2001). Activated microglia in the human glaucomatous optic nerve head. J. Neurosci. Res. 64, 523-532. doi: 10.1002/jnr.1104
290. Yucel, Y. H., Zhang, Q., Weinreb, R. N., Kaufman, P. L., and Gupta, N. (2003). Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Prog. Retin. Eye Res. 22, 465-481. doi: 10.1016/S1350-9462(03)00026-0
291. Yuruker, V., Naziroglu, M., and Senol, N. (2015). Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: possible involvement of TRPM2 channels. Metab. Brain Dis. 30, 223-231. doi: 10.1007/s11011-014-9623-3
292. Zecca, L., Wilms, H., Geick, S., Claasen, J. H., Brandenburg, L. O., Holzknecht, C., et al. (2008). Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson's disease. Acta Neuropathol. 116, 47-55. doi: 10.1007/s00401-008-0361-7
293. Zhang, Q. S., Heng, Y., Yuan, Y. H., and Chen, N. H. (2017). Pathological alpha-synuclein exacerbates the progression of Parkinson's disease through microglial activation. Toxicol Lett 265, 30-37. doi: 10.1016/j.toxlet.2016.11.002
294. Zhang, S., Wang, X.-J., Tian, L.-P., Pan, J., Lu, G.-Q., Zhang, Y.-J., et al. (2011). CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease. J. Neuroinflammat. 8:154. doi: 10.1186/1742-2094-8-154
295. Zhou, X., He, X., and Ren, Y. (2014). Function of microglia and macrophages in secondary damage after spinal cord injury. Neural Regen. Res 9, 1787-1795. doi: 10.4103/1673-5374.143423