Photoreceptor proteins initiate microglial activation via toll-like receptor 4 in retinal degeneration mediated by all-trans-retinal

Journal of Biological Chemistry

Volumn 288, Issue 21, 2013, Pages 15326-15341

  Kohno, Hideo ^a,c   Chen, Yu ^a,d   Kevany, Brian M ^a   Pearlman, Eric ^a   Miyagi, Masaru ^a,b   Maeda, Tadao ^a   Palczewski, Krzysztof ^a   Maeda, Akiko ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CASE WESTERN RESERVE UNIVERSITY   (United States)

^c JIKEI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^d SHANGHAI UNIVERSITY OF TRADITIONAL CHINESE MEDICINE   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDES; ANTIGEN-ANTIBODY REACTIONS; CELL DEATH; CHEMICAL ACTIVATION; LIGANDS; MAMMALS; OPHTHALMOLOGY; PROTEINS; VISION;

MACROPHAGE ACTIVATION; MICE MODELS; MICROGLIA; MICROGLIAL ACTIVATIONS; PHAGOCYTOSE; PHOTORECEPTOR PROTEINS; RETINAL DEGENERATIONS; RETINAL PIGMENT EPITHELIUM; STARGARDT DISEASE; TOLL-LIKE RECEPTOR 4;

PATHOLOGY;

CHEMOKINE; CYTOKINE; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; PHOTORECEPTOR PROTEIN; RECEPTOR PROTEIN; RETINAL; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL ACTIVATION; CELL ISOLATION; CONTROLLED STUDY; CYTOTOXICITY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HISTOLOGY; INNATE IMMUNITY; MACROPHAGE; MALE; MICROGLIA; MOUSE; NONHUMAN; PATHOGENESIS; PHAGOCYTOSIS; PHENOTYPE; PIGMENT EPITHELIUM; PRIORITY JOURNAL; RETINA; RETINA MACULA AGE RELATED DEGENERATION; RETINITIS PIGMENTOSA; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCANNING LASER OPHTHALMOSCOPY; SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY; STARGARDT DISEASE; WILD TYPE;

EID: 84878264043     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.448712     Document Type: Article

References (89)

1. Friedman, D. S., O'Colmain, B. J., Muñoz, B., Tomany, S. C., McCarty, C., de Jong, P. T., Nemesure, B., Mitchell, P., and Kempen, J. (2004) Prevalence of age-related macular degeneration in the United States. Arch. Ophthalmol. 122, 564-572 (Pubitemid 38456293)
2. Molday, R. S., and Zhang, K. (2010) Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration. Prog. Lipid Res. 49, 476-492
3. Berger, W., Kloeckener-Gruissem, B., and Neidhardt, J. (2010) The molecular basis of human retinal and vitreoretinal diseases. Prog. Retin. Eye Res. 29, 335-375
4. Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J., Silvestri, G., Russell, S. R., Klaver, C. C., Barbazetto, I., Chang, S., Yannuzzi, L. A., Barile, G. R., Merriam, J. C., Smith, R. T., Olsh, A. K., Bergeron, J., Zernant, J., Merriam, J. E., Gold, B., Dean, M., and Allikmets, R. (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 102, 7227-7232 (Pubitemid 40696361)
5. Edwards, A. O., Ritter, R., 3rd, Abel, K. J., Manning, A., Panhuysen, C., and Farrer, L. A. (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308, 421-424 (Pubitemid 40530082)
6. Allikmets, R., Shroyer, N. F., Singh, N., Seddon, J. M., Lewis, R. A., Bernstein, P. S., Peiffer, A., Zabriskie, N. A., Li, Y., Hutchinson, A., Dean, M., Lupski, J. R., and Leppert, M. (1997) Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 277, 1805-1807 (Pubitemid 27449189)
7. Dryja, T. P., McGee, T. L., Reichel, E., Hahn, L. B., Cowley, G. S., Yandell, D. W., Sandberg, M. A., and Berson, E. L. (1990) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343, 364-366
8. Medzhitov, R. (2008) Origin and physiological roles of inflammation. Nature 454, 428-435
9. Xu, H., Chen, M., and Forrester, J. V. (2009) Para-inflammation in the aging retina. Prog. Retin. Eye Res. 28, 348-368
10. Joly, S., Francke, M., Ulbricht, E., Beck, S., Seeliger, M., Hirrlinger, P., Hirrlinger, J., Lang, K. S., Zinkernagel, M., Odermatt, B., Samardzija, M., Reichenbach, A., Grimm, C., and Remé, C. E. (2009) Cooperative phagocytes. Resident microglia and bone marrow immigrants remove dead photoreceptors in retinal lesions. Am. J. Pathol. 174, 2310-2323
11. Ding, X., Patel, M., and Chan, C. C. (2009) Molecular pathology of agerelated macular degeneration. Prog. Retin. Eye Res. 28, 1-18
12. Gupta, N., Brown, K. E., and Milam, A. H. (2003) Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp. Eye Res. 76, 463-471 (Pubitemid 36299058)
13. Radu, R. A., Hu, J., Yuan, Q., Welch, D. L., Makshanoff, J., Lloyd, M., McMullen, S., Travis, G. H., and Bok, D. (2011) Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration. J. Biol. Chem. 286, 18593-18601
14. Zhou, J., Jang, Y. P., Kim, S. R., and Sparrow, J. R. (2006) Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc. Natl. Acad. Sci. U.S.A. 103, 16182-16187 (Pubitemid 44715171)
15. Maeda, A., Golczak, M., Chen, Y., Okano, K., Kohno, H., Shiose, S., Ishikawa, K., Harte, W., Palczewska, G., Maeda, T., and Palczewski, K. (2012) Primary amines protect against retinal degeneration in mouse models of retinopathies. Nat. Chem. Biol. 8, 170-178
16. Maeda, A., Maeda, T., Golczak, M., and Palczewski, K. (2008) Retinopathy in mice induced by disrupted all-trans-retinal clearance. J. Biol. Chem. 283, 26684-26693
17. Shiose, S., Chen, Y., Okano, K., Roy, S., Kohno, H., Tang, J., Pearlman, E., Maeda, T., Palczewski, K., and Maeda, A. (2011) Toll-like receptor 3 is required for development of retinopathy caused by impaired all-transretinal clearance in mice. J. Biol. Chem. 286, 15543-15555
18. Haeseleer, F., Jang, G. F., Imanishi, Y., Driessen, C. A., Matsumura, M., Nelson, P. S., and Palczewski, K. (2002) Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina. J. Biol. Chem. 277, 45537-45546 (Pubitemid 36159164)
19. Maeda, A., Maeda, T., Imanishi, Y., Kuksa, V., Alekseev, A., Bronson, J. D., Zhang, H., Zhu, L., Sun, W., Saperstein, D. A., Rieke, F., Baehr, W., and Palczewski, K. (2005) Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo. J. Biol. Chem. 280, 18822-18832 (Pubitemid 41379584)
20. Ma, W., Zhao, L., Fontainhas, A.M., Fariss, R. N., and Wong, W. T. (2009) Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells. A potential cellular interaction relevant to AMD. PLoS One 4, e7945
21. Johnson, A. C., Li, X., and Pearlman, E. (2008) MyD88 functions as a negative regulator of TLR3/TRIF-induced corneal inflammation by inhibiting activation of c-Jun N-terminal kinase. J. Biol. Chem. 283, 3988-3996
22. Diemer, T., Gibbs, D., and Williams, D. S. (2008) Analysis of the rate of disk membrane digestion by cultured RPE cells. Adv. Exp. Med. Biol. 613, 321-326
23. Liang, Y., Fotiadis, D., Filipek, S., Saperstein, D. A., Palczewski, K., and Engel, A. (2003) Organization of theGprotein-coupled receptors rhodopsin and opsin in native membranes. J. Biol. Chem. 278, 21655-21662 (Pubitemid 36792566)
24. Maeda, A., Maeda, T., Golczak, M., Chou, S., Desai, A., Hoppel, C. L., Matsuyama, S., and Palczewski, K. (2009) Involvement of all-trans-retinal in acute light-induced retinopathy of mice. J. Biol. Chem. 284, 15173-15183
25. Chen, M., Forrester, J. V., and Xu, H. (2011) Dysregulation in retinal para-inflammation and age-related retinal degeneration in CCL2 or CCR2 deficient mice. PLoS One 6, e22818
26. Ambati, J., Anand, A., Fernandez, S., Sakurai, E., Lynn, B. C., Kuziel, W. A., Rollins, B. J., and Ambati, B. K. (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat. Med. 9, 1390-1397 (Pubitemid 37466188)
27. Tuo, J., Smith, B. C., Bojanowski, C. M., Meleth, A. D., Gery, I., Csaky, K. G., Chew, E. Y., and Chan, C. C. (2004) The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration. FASEB J. 18, 1297-1299 (Pubitemid 39561582)
28. Lavalette, S., Raoul, W., Houssier, M., Camelo, S., Levy, O., Calippe, B., Jonet, L., Behar-Cohen, F., Chemtob, S., Guillonneau, X., Combadière, C., and Sennlaub, F. (2011) Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration. Am. J. Pathol. 178, 2416-2423
29. Xu, J., Zhu, D., He, S., Spee, C., Ryan, S. J., and Hinton, D. R. (2011) Transcriptional regulation of bone morphogenetic protein 4 by tumor necrosis factor and its relationship with age-related macular degeneration. FASEB J. 25, 2221-2233
30. Lichtlen, P., Lam, T. T., Nork, T. M., Streit, T., and Urech, D. M. (2010) Relative contribution of VEGF and TNF-α in the cynomolgus laser-induced CNV model. Comparing the efficacy of bevacizumab, adalimumab, and ESBA105. Invest. Ophthalmol. Vis. Sci. 51, 4738-4745
31. Theodossiadis, P. G., Liarakos, V. S., Sfikakis, P. P., Vergados, I. A., and Theodossiadis, G. P. (2009) Intravitreal administration of the anti-tumor necrosis factor agent infliximab for neovascular age-related macular degeneration. Am. J. Ophthalmol. 147, 825-830
32. Anderson, D. H., Mullins, R. F., Hageman, G. S., and Johnson, L. V. (2002) A role for local inflammation in the formation of drusen in the aging eye. Am. J. Ophthalmol. 134, 411-431
33. Witmer, A. N., Vrensen, G. F., Van Noorden, C. J., and Schlingemann, R. O. (2003) Vascular endothelial growth factors and angiogenesis in eye disease. Prog. Retin. Eye Res. 22, 1-29 (Pubitemid 36207453)
34. Cai, J., Wu, L., Qi, X., Li Calzi, S., Caballero, S., Shaw, L., Ruan, Q., Grant, M. B., and Boulton, M. E. (2011) PEDF regulates vascular permeability by a γ-secretase-mediated pathway. PLoS One 6, e21164
35. Kaur, C., Foulds, W. S., and Ling, E. A. (2008) Blood-retinal barrier in hypoxic ischaemic conditions. basic concepts, clinical features and management. Prog. Retin. Eye Res. 27, 622-647
36. Joussen, A. M., Murata, T., Tsujikawa, A., Kirchhof, B., Bursell, S. E., and Adamis, A. P. (2001) Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am. J. Pathol. 158, 147-152 (Pubitemid 32096479)
37. Seitz, H. M., Camenisch, T. D., Lemke, G., Earp, H. S., and Matsushima, G. K. (2007) Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J. Immunol. 178, 5635-5642 (Pubitemid 46674359)
38. Nandrot, E. F., and Dufour, E. M. (2010) Mertk in daily retinal phagocytosis. A history in the making. Adv. Exp. Med. Biol. 664, 133-140
39. Duncan, J. L., LaVail, M. M., Yasumura, D., Matthes, M. T., Yang, H., Trautmann, N., Chappelow, A. V., Feng, W., Earp, H. S., Matsushima, G. K., and Vollrath, D. (2003) An RCS-like retinal dystrophy phenotype in mer knockout mice. Invest. Ophthalmol. Vis. Sci. 44, 826-838 (Pubitemid 36159735)
40. Kevany, B.M., and Palczewski, K. (2010) Phagocytosis of retinal rod and cone photoreceptors. Physiology 25, 8-15
41. Palczewski, K. (2010) Retinoids for treatment of retinal diseases. Trends Pharmacol. Sci. 31, 284-295
42. Nussenblatt, R. B., and Ferris, F., 3rd. (2007) Age-related macular degeneration and the immune response. Implications for therapy. Am. J. Ophthalmol. 144, 618-626
43. Yoshida, A., Elner, S. G., Bian, Z. M., Kindezelskii, A. L., Petty, H. R., and Elner, V. M. (2003) Activated monocytes induce human retinal pigment epithelial cell apoptosis through caspase-3 activation. Lab. Invest. 83, 1117-1129 (Pubitemid 37013047)
44. Fishel, S., Jackson, P., Webster, J., and Faratian, B. (1988) Endotoxins in culture medium for human in vitro fertilization. Fertil. Steril. 49, 108-111 (Pubitemid 18033901)
45. Kadiyala, C. S., Tomechko, S. E., and Miyagi, M. (2010) Perfluorooctanoic acid for shotgun proteomics. PLoS One 5, e15332
46. Kono, H., and Rock, K. L. (2008) How dying cells alert the immune system to danger. Nat. Rev. Immunol. 8, 279-289 (Pubitemid 351432799)
47. Shichita, T., Hasegawa, E., Kimura, A., Morita, R., Sakaguchi, R., Takada, I., Sekiya, T., Ooboshi, H., Kitazono, T., Yanagawa, T., Ishii, T., Takahashi, H., Mori, S., Nishibori, M., Kuroda, K., Akira, S., Miyake, K., and Yoshimura, A. (2012) Peroxiredoxin family proteins are key initiators of postischemic inflammation in the brain. Nat. Med. 18, 911-917
48. Erridge, C. (2010) Endogenous ligands of TLR2 and TLR4. Agonists or assistants? J. Leukocyte Biol. 87, 989-999
49. van Rooijen, N., and van Kesteren-Hendrikx, E. (2002) Clodronate liposomes. Perspectives in research and therapeutics. J. Liposome Res. 12, 81-94
50. Van Rooijen, N., and Sanders, A. (1994) Liposome mediated depletion of macrophages. Mechanism of action, preparation of liposomes and applications. J. Immunol. Methods 174, 83-93
51. Wu, D. C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D. K., Ischiropoulos, H., and Przedborski, S. (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine mouse model of Parkinson disease. J. Neurosci. 22, 1763-1771 (Pubitemid 35386294)
52. Filipovic, R., and Zecevic, N. (2008) Neuroprotective role of minocycline in co-cultures of human fetal neurons and microglia. Exp. Neurol. 211, 41-51
53. Wang, A. L., Yu, A. C., Lau, L. T., Lee, C., Wu le, M., Zhu, X., and Tso, M. O. (2005) Minocycline inhibits LPS-induced retinal microglia activation. Neurochem. Int. 47, 152-158 (Pubitemid 40848704)
54. Zhao, L., Ma, W., Fariss, R. N., and Wong, W. T. (2011) Minocycline attenuates photoreceptor degeneration in a mouse model of subretinal hemorrhage microglial. Inhibition as a potential therapeutic strategy. Am. J. Pathol. 179, 1265-1277
55. Bauer, M., Goldstein, M., Christmann, M., Becker, H., Heylmann, D., and Kaina, B. (2011) Human monocytes are severely impaired in base and DNA double-strand break repair that renders them vulnerable to oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 108, 21105-21110
56. Chen, X., Ma, X., Jiang, Y., Pi, R., Liu, Y., and Ma, L. (2011) The prospects of minocycline in multiple sclerosis. J. Neuroimmunol. 235, 1-8
57. Imai, Y., Ibata, I., Ito, D., Ohsawa, K., and Kohsaka, S. (1996) A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem. Biophys. Res. Commun. 224, 855-862 (Pubitemid 26278674)
58. Ji, K. A., Yang, M. S., Jeong, H. K., Min, K. J., Kang, S. H., Jou, I., and Joe, E. H. (2007) Resident microglia die and infiltrated neutrophils and monocytes become major inflammatory cells in lipopolysaccharide-injected brain. Glia 55, 1577-1588 (Pubitemid 47556261)
59. Maeda, A., Okano, K., Park, P. S., Lem, J., Crouch, R. K., Maeda, T., and Palczewski, K. (2010) Palmitoylation stabilizes unliganded rod opsin. Proc. Natl. Acad. Sci. U.S.A. 107, 8428-8433
60. Luhmann, U. F., Robbie, S., Munro, P. M., Barker, S. E., Duran, Y., Luong, V., Fitzke, F. W., Bainbridge, J. W., Ali, R. R., and MacLaren, R. E. (2009) The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages. Invest. Ophthalmol. Vis. Sci. 50, 5934-5943
61. Beltran, W. A., Acland, G. M., and Aguirre, G. D. (2009) Age-dependent disease expression determines remodeling of the retinal mosaic in carriers of RPGR exon ORF15 mutations. Invest. Ophthalmol. Vis. Sci. 50, 3985-3995
62. Gu, D., Beltran, W. A., Pearce-Kelling, S., Li, Z., Acland, G. M., and Aguirre, G. D. (2009) Steroids do not prevent photoreceptor degeneration in the light-exposed T4R rhodopsin mutant dog retina irrespective of AP-1 inhibition. Invest. Ophthalmol. Vis. Sci. 50, 3482-3494
63. Sugita, S., Seki, K., Yokozawa, K., Tochigi, N., Furuta, K., Hisaoka, M., Hashimoto, H., Shimoda, T., and Hasegawa, T. (2009) Analysis of CHOP rearrangement in pleomorphic liposarcomas using fluorescence in situ hybridization. Cancer Sci. 100, 82-87
64. Usui, Y., Okunuki, Y., Hattori, T., Kezuka, T., Keino, H., Ebihara, N., Sugita, S., Usui, M., Goto, H., and Takeuchi, M. (2008) Functional expression of B7H1 on retinal pigment epithelial cells. Exp. Eye Res. 86, 52-59 (Pubitemid 350212878)
65. Chen, H., Liu, B., Lukas, T. J., and Neufeld, A. H. (2008) The aged retinal pigment epithelium/choroid. A potential substratum for the pathogenesis of age-related macular degeneration. PLoS One 3, e2339
66. Maeda, A., Golczak, M., Maeda, T., and Palczewski, K. (2009) Limited roles of Rdh8, Rdh12, and Abca4 in all-trans-retinal clearance in mouse retina. Invest. Ophthalmol. Vis. Sci. 50, 5435-5443
67. Scott, R. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S., and Matsushima, G. K. (2001) Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411, 207-211 (Pubitemid 32455181)
68. Xu, H., Dawson, R., Forrester, J. V., and Liversidge, J. (2007) Identification of novel dendritic cell populations in normal mouse retina. Invest. Ophthalmol. Vis. Sci. 48, 1701-1710 (Pubitemid 351261356)
69. Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz-Boutaud, N., Agarwal, A., Postel, E. A., and Pericak-Vance, M. A. (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308, 419-421 (Pubitemid 40530081)
70. Yates, J. R., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., Armbrecht, A. M., Dhillon, B., Deary, I. J., Redmond, E., Bird, A. C., Moore, A. T., and Genetic Factors inAMDStudy Group. (2007) Complement C3 variant and the risk of age-related macular degeneration. N. Engl. J. Med. 357, 553-561 (Pubitemid 47236280)
71. Yang, Z., Stratton, C., Francis, P. J., Kleinman, M. E., Tan, P. L., Gibbs, D., Tong, Z., Chen, H., Constantine, R., Yang, X., Chen, Y., Zeng, J., Davey, L., Ma, X., Hau, V. S., Wang, C., Harmon, J., Buehler, J., Pearson, E., Patel, S., Kaminoh, Y., Watkins, S., Luo, L., Zabriskie, N. A., Bernstein, P. S., Cho, W., Schwager, A., Hinton, D. R., Klein, M. L., Hamon, S. C., Simmons, E., Yu, B., Campochiaro, B., Sunness, J. S., Campochiaro, P., Jorde, L., Parmigiani, G., Zack, D. J., Katsanis, N., Ambati, J., and Zhang, K. (2008) Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N. Engl. J. Med. 359, 1456-1463
72. Zareparsi, S., Buraczynska, M., Branham, K. E., Shah, S., Eng, D., Li, M., Pawar, H., Yashar, B. M., Moroi, S. E., Lichter, P. R., Petty, H. R., Richards, J. E., Abecasis, G. R., Elner, V. M., and Swaroop, A. (2005) Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. Hum. Mol. Genet. 14, 1449-1455 (Pubitemid 40834203)
73. Edwards, A. O., Chen, D., Fridley, B. L., James, K. M., Wu, Y., Abecasis, G., Swaroop, A., Othman, M., Branham, K., Iyengar, S. K., Sivakumaran, T. A., Klein, R., Klein, B. E., and Tosakulwong, N. (2008) Toll-like receptor polymorphisms and age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 49, 1652-1659
74. Cho, Y., Wang, J. J., Chew, E. Y., Ferris, F. L., 3rd, Mitchell, P., Chan, C. C., and Tuo, J. (2009) Toll-like receptor polymorphisms and age-related macular degeneration. Replication in three case-control samples. Invest. Ophthalmol. Vis. Sci. 50, 5614-5618
75. Ko, M. K., Saraswathy, S., Parikh, J. G., and Rao, N. A. (2011) The role of TLR4 activation in photoreceptor mitochondrial oxidative stress. Invest. Ophthalmol. Vis. Sci. 52, 5824-5835
76. Sen, A., Chowdhury, I. H., Mukhopadhyay, D., Paine, S. K., Mukherjee, A., Mondal, L. K., Chatterjee, M., and Bhattacharya, B. (2011) Increased Tolllike receptor-2 expression on nonclassic CD16 monocytes from patients with inflammatory stage of Eales' disease. Invest. Ophthalmol. Vis. Sci. 52, 6940-6948
77. Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., Albuquerque, R. J., Hauswirth, W. W., Chiodo, V. A., Kugel, J. F., Goodrich, J. A., Ponicsan, S. L., Chaudhuri, G., Murphy, M. P., Dunaief, J. L., Ambati, B. K., Ogura, Y., Yoo, J. W., Lee, D. K., Provost, P., Hinton, D. R., Núñez, G., Baffi, J. Z., Kleinman, M. E., and Ambati, J. (2012) DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 149, 847-859
78. Kleinman, M. E., Kaneko, H., Cho, W. G., Dridi, S., Fowler, B. J., Blandford, A. D., Albuquerque, R. J., Hirano, Y., Terasaki, H., Kondo, M., Fujita, T., Ambati, B. K., Tarallo, V., Gelfand, B. D., Bogdanovich, S., Baffi, J. Z., Ambati, J. (2012) Short-interfering RNAs induce retinal degeneration via TLR3 and IRF3. Mol. Ther. 20, 101-108
79. Lehnardt, S. (2010) Innate immunity and neuroinflammation in the CNS. The role of microglia in Toll-like receptor-mediated neuronal injury. Glia 58, 253-263
80. Owens, T. (2009) Toll-like receptors in neurodegeneration. Curr. Top. Microbiol. Immunol. 336, 105-120
81. West, X. Z., Malinin, N. L., Merkulova, A. A., Tischenko, M., Kerr, B. A., Borden, E. C., Podrez, E. A., Salomon, R. G., and Byzova, T. V. (2010) Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature 467, 972-976
82. Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A., Nacken, W., Foell, D., van der Poll, T., Sorg, C., and Roth, J. (2007) Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat. Med. 13, 1042-1049 (Pubitemid 47517513)
83. Thériault, J. R., Mambula, S. S., Sawamura, T., Stevenson, M. A., and Calderwood, S. K. (2005) Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells. FEBS Lett. 579, 1951-1960 (Pubitemid 40404037)
84. Asea, A., Rehli, M., Kabingu, E., Boch, J. A., Bare, O., Auron, P. E., Stevenson, M. A., and Calderwood, S. K. (2002) Novel signal transduction pathway utilized by extracellular HSP70. Role of Toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277, 15028-15034 (Pubitemid 34952579)
85. Sanyal, S., De Ruiter, A., and Hawkins, R. K. (1980) Development and degeneration of retina in rds mutant mice. Light microscopy. J. Comp. Neurol. 194, 193-207 (Pubitemid 11212701)
86. Xu, H., Chen, M., Manivannan, A., Lois, N., and Forrester, J. V. (2008) Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice. Aging Cell 7, 58-68
87. Bruban, J., Maoui, A., Chalour, N., An, N., Jonet, L., Feumi, C., Tréton, J., Sennlaub, F., Behar-Cohen, F., Mascarelli, F., and Dinet, V. (2011) CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis. Neurobiol. Dis. 42, 55-72
88. Sasahara, M., Otani, A., Oishi, A., Kojima, H., Yodoi, Y., Kameda, T., Nakamura, H., and Yoshimura, N. (2008) Activation of bone marrow-derived microglia promotes photoreceptor survival in inherited retinal degeneration. Am. J. Pathol. 172, 1693-1703 (Pubitemid 351793360)
89. Henkel, J. S., Beers, D. R., Zhao, W., and Appel, S. H. (2009) Microglia in ALS. The good, the bad, and the resting. J. Neuroimmune Pharmacol. 4, 389-398