Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

Journal of Diabetes Research

Volumn 2016, Issue , 2016, Pages

  Hernández, Cristina ^a   Dal Monte, Massimo ^b   Simó, Rafael ^a   Casini, Giovanni ^b  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^b UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

NUTRACEUTICAL; VASCULOTROPIN; ANGIOGENESIS INHIBITOR; NEUROPROTECTIVE AGENT; VASCULOTROPIN A;

DIABETIC RETINOPATHY; HUMAN; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; PATHOGENESIS; RETINA DEGENERATION; REVIEW; SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY; SURVIVAL FACTOR; UPREGULATION; VISUAL IMPAIRMENT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL PROTECTION; DRUG EFFECTS; METABOLISM; PARACRINE SIGNALING; PATHOLOGY; RETINA BLOOD VESSEL; RETINA NERVE CELL; SIGNAL TRANSDUCTION;

ANGIOGENESIS INHIBITORS; ANIMALS; CYTOPROTECTION; DIABETIC RETINOPATHY; HUMANS; NERVE DEGENERATION; NEUROPROTECTIVE AGENTS; PARACRINE COMMUNICATION; RETINAL NEURONS; RETINAL VESSELS; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84971492792     PISSN: 23146745     EISSN: 23146753     Source Type: Journal    
DOI: 10.1155/2016/9508541     Document Type: Review

References (241)

1. S. F. Abcouwer and T. W. Gardner, "Diabetic retinopathy: loss of neuroretinal adaptation to the diabeticmetabolic environment, " Annals of the New York Academy of Sciences, vol. 1311, pp. 174-190, 2014.
2. M. S. Ola, M. I. Nawaz, M. M. Siddiquei, S. Al-Amro, and A. M. Abu El-Asrar, "Recent advances in understanding the biochemical andmolecularmechanismof diabetic retinopathy, " Journal of Diabetes and Its Complications, vol. 26, no. 1, pp. 56-64, 2012.
3. H. Qian and H. Ripps, "Neurovascular interaction and the pathophysiology of diabetic retinopathy, " Experimental Diabetes Research, vol. 2011, Article ID 693426, 11 pages, 2011.
4. J. M. Tarr, K. Kaul, M. Chopra, E. M. Kohner, and R. Chibber, "Pathophysiology of diabetic retinopathy, " ISRN Ophthalmology, vol. 2013, Article ID 343560, 13 pages, 2013.
5. D. A. Antonetti, A. J. Barber, S. K. Bronson et al., "Diabetic retinopathy: seeing beyond glucose-induced microvascular disease, " Diabetes, vol. 55, no. 9, pp. 2401-2411, 2006.
6. C. Hernández and R. Simó, "Neuroprotection in diabetic retinopathy, " Current Diabetes Reports, vol. 12, no. 4, pp. 329-337, 2012.
7. V. Jindal, "Neurodegeneration as a primary change and role of neuroprotection in diabetic retinopathy, " Molecular Neurobiology, vol. 51, no. 3, pp. 878-884, 2015.
8. X. Zhang, N. Wang, G. R. Barile, S. Bao, and M. Gillies, "Diabetic retinopathy: neuron protection as a therapeutic target, " International Journal of Biochemistry and Cell Biology, vol. 45, no. 7, pp. 1525-1529, 2013.
9. R. Simó and C. Hernández, "Novel approaches for treating diabetic retinopathy based on recent pathogenic evidence, " Progress in Retinal and Eye Research, vol. 48, pp. 160-180, 2015.
10. A. J. Barber, E. Lieth, S. A. Khin, D. A. Antonetti, A. G. Buchanan, and T. W. Gardner, "Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin, "The Journal of Clinical Investigation, vol. 102, no. 4, pp. 783-791, 1998.
11. Q. Yang, Y. Xu, P. Xie et al., "Retinal neurodegeneration in db/db mice at the early period of diabetes, " Journal of Ophthalmology, vol. 2015, Article ID757412, 9 pages, 2015.
12. M. Villarroel, A. Ciudin, C. Hernandez, and R. Simo, "Neurodegeneration: an early event of diabetic retinopathy, " World Journal of Diabetes, vol. 1, no. 2, pp. 57-64, 2010.
13. A. J. Adams and M. A. Bearse Jr., "Retinal neuropathy precedes vasculopathy in diabetes: a function-based opportunity for early treatment intervention" Clinical and Experimental Optometry, vol. 95, no. 3, pp. 256-265, 2012.
14. A. J. Barber, "A new view of diabetic retinopathy: a neurodegenerative disease of the eye, " Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 27, no. 2, pp. 283-290, 2003.
15. R. A. Feit-Leichman, R. Kinouchi, M. Takeda et al., "Vascular damage in a mouse model of diabetic retinopathy: relation to neuronal and glial changes, " Investigative Ophthalmology and Visual Science, vol. 46, no. 11, pp. 4281-4287, 2005.
16. J. Yu, L. Wang, S.-J. Weng, X.-L. Yang, D.-Q. Zhang, and Y.-M. Zhong, "Hyperactivity of ON-type retinal ganglion cells in streptozotocin-induced diabetic mice, " PLoS ONE, vol. 8, no. 9, Article ID e76049, 2013.
17. R. A. Gubitosi-Klug, R. Talahalli, Y. Du, J. L. Nadler, and T. S. Kern, "5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy, " Diabetes, vol. 57, no. 5, pp. 1387-1393, 2008.
18. A. M. Abu-El-Asrar, L. Dralands, L. Missotten, I. A. Al-Jadaan, and K. Geboes, "Expression of apoptosismarkers in the retinas of human subjects with diabetes, " Investigative Ophthalmology and Visual Science, vol. 45, no. 8, pp. 2760-2766, 2004.
19. T. Oshitari, S. Yamamoto, N. Hata, and S. Roy, "Mitochondriaand caspase-dependent cell death pathway involved in neuronal degeneration in diabetic retinopathy, " British Journal of Ophthalmology, vol. 92, no. 4, pp. 552-556, 2008.
20. A. M. Abu El-Asrar, L. Dralands, L. Missotten, and K. Geboes, "Expression of antiapoptotic and proapoptotic molecules in diabetic retinas, " Eye, vol. 21, no. 2, pp. 238-245, 2007.
21. H. W. van Dijk, P. H. B. Kok, M. Garvin et al., "Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy, " Investigative Ophthalmology and Visual Science, vol. 50, no. 7, pp. 3404-3409, 2009.
22. H. W. van Dijk, F. D. Verbraak, P. H. B. Kok et al., "Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes, " Investigative Ophthalmology and Visual Science, vol. 51, no. 7, pp. 3660-3665, 2010.
23. H. W. van Dijk, F. D. Verbraak, P. H. Kok et al., "Early neurodegeneration in the retina of type 2 diabetic patients, " Investigative Opthalmology & Visual Science, vol. 53, no. 6, pp. 2715-2719, 2012.
24. J. Chhablani, A. Sharma, A. Goud et al., "Neurodegeneration in type 2 diabetes: evidence from spectral-domain optical coherence tomography, " InvestigativeOphthalmology and Visual Science, vol. 56, no. 11, pp. 6333-6338, 2015.
25. A. J. Barber, D. A. Antonetti, T. S. Kern et al., "The Ins2Akita mouse as a model of early retinal complications in diabetes, " Investigative Ophthalmology and Visual Science, vol. 46, no. 6, pp. 2210-2218, 2005.
26. P. M. Martin, P. Roon, T. K. Van Ells, V. Ganapathy, and S. B. Smith, "Death of retinal neurons in streptozotocin-induced diabetic mice, " Investigative Ophthalmology and Visual Science, vol. 45, no. 9, pp. 3330-3336, 2004.
27. Y.-H. Li, Y.-H. Zhuo, L. Lü et al., "Caspase-dependent retinal ganglion cell apoptosis in the rat model of acute diabetes, " Chinese Medical Journal, vol. 121, no. 24, pp. 2566-2571, 2008.
28. R. A. Kowluru and S. N. Abbas, "Diabetes-induced mitochondrial dysfunction in the retina, " InvestigativeOphthalmology and Visual Science, vol. 44, no. 12, pp. 5327-5334, 2003.
29. P. Bogdanov, L. Corraliza, J. A. Villena et al., "The db/dbmouse: a useful model for the study of diabetic retinal neurodegeneration, " PLoS ONE, vol. 9, no. 5, Article ID e97302, 2014.
30. J. H. Yang, H. W. Kwak, T. G. Kim, J. Han, S. W. Moon, and S. Y. Yu, "Retinal neurodegeneration in type II diabetic Otsuka long-evans Tokushima fatty rats, " Investigative Ophthalmology and Visual Science, vol. 54, no. 6, pp. 3844-3851, 2013.
31. F. I. Baptista, M. J. Pinto, F. Elvas, T. Martins, R. D. Almeida, and A. F. Ambrósio, "Diabetes induces changes inKIF1A, KIF5B and dynein distribution in the rat retina: implications for axonal transport, " Experimental Eye Research, vol. 127, pp. 91-103, 2014.
32. T. S. D'Cruz, B. N. Weibley, S. R. Kimball, and A. J. Barber, "Posttranslational processing of synaptophysin in the rat retina is disrupted by diabetes, " PLoSONE, vol. 7, no. 9, Article IDe44711, 2012.
33. J. M. Gaspar, F. I. Baptista, J. Galvão, á. F. Castilho, R. A. Cunha, and A. F. Ambrósio, "Diabetes differentially affects the content of exocytotic proteins in hippocampal and retinal nerve terminals, " Neuroscience, vol. 169, no. 4, pp. 1589-1600, 2010.
34. H. D. VanGuilder, R. M. Brucklacher, K. Patel, R. W. Ellis, W. M. Freeman, and A. J. Barber, "Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina, " European Journal of Neuroscience, vol. 28, no. 1, pp. 1-11, 2008.
35. T. S. Kern and A. J. Barber, "Retinal ganglion cells in diabetes, " Journal of Physiology, vol. 586, no. 18, pp. 4401-4408, 2008.
36. X. Liu, Z. Zuo, W. Liu et al., "Upregulation of Nogo receptor expression induces apoptosis of retinal ganglion cells in diabetic rats, " Neural Regeneration Research, vol. 9, no. 8, pp. 815-820, 2014.
37. K. Szabadfi, T. Atlasz, P. Kiss et al., "Protective effects of the neuropeptide PACAP in diabetic retinopathy, " Cell and Tissue Research, vol. 348, no. 1, pp. 37-46, 2012.
38. T. K. Ali, S. Matragoon, B. A. Pillai, G. I. Liou, and A. B. El-Remessy, "Peroxynitrite mediates retinal neurodegeneration by inhibiting nerve growth factor survival signaling in experimental and human diabetes, " Diabetes, vol. 57, no. 4, pp. 889-898, 2008.
39. M. J. Gastinger, R. S. J. Singh, and A. J. Barber, "Loss of cholinergic and dopaminergic amacrine cells in streptozotocindiabetic rat and Ins2Akita-diabetic mouse retinas, " Investigative Ophthalmology & Visual Science, vol. 47, no. 7, pp. 3143-3150, 2006.
40. M. Seki, T. Tanaka, H. Nawa et al., "Involvement of brainderived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells, " Diabetes, vol. 53, no. 9, pp. 2412-2419, 2004.
41. E. Roufail, T. Soulis, E. Boel, M. E. Cooper, and S. Rees, "Depletion of nitric oxide synthase-containing neurons in the diabetic retina: reversal by aminoguanidine, " Diabetologia, vol. 41, no. 12, pp. 1419-1425, 1998.
42. M. H. Aung, H. N. Park, M. K. Han et al., "Dopamine deficiency contributes to early visual dysfunction in a rodent model of type 1 diabetes, " The Journal of Neuroscience, vol. 34, no. 3, pp. 726-736, 2014.
43. F. I. Baptista, J. M. Gaspar, A. Cristóvão, P. F. Santos, A. Köfalvi, and A. F. Ambrósio, "Diabetes induces early transient changes in the content of vesicular transporters and no major effects in neurotransmitter release in hippocampus and retina, " Brain Research, vol. 1383, pp. 257-269, 2011.
44. S.-H. Park, J.-W. Park, S.-J. Park et al., "Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina, " Diabetologia, vol. 46, no. 9, pp. 1260-1268, 2003.
45. Y. Aizu, K. Oyanagi, J. Hu, and H. Nakagawa, "Degeneration of retinal neuronal processes and pigment epithelium in the early stage of the streptozotocin-diabetic rats, " Neuropathology, vol. 22, no. 3, pp. 161-170, 2002.
46. S. V. Logvinov, M. B. Plotnikov, A. A. Zhdankina et al., "Morphological changes in retinal neurons in streptozotocininduced diabetes mellitus and their correction with an isobornylphenol derivative, " Neuroscience and Behavioral Physiology, vol. 40, no. 7, pp. 779-782, 2010.
47. M. Lombardo, M. Parravano, G. Lombardo et al., "Adaptive optics imaging of parafoveal cones in type 1 diabetes, " Retina, vol. 34, no. 3, pp. 546-557, 2014.
48. T. S. Kern and B. A. Berkowitz, "Photoreceptors in diabetic retinopathy, " Journal of Diabetes Investigation, vol. 6, no. 4, pp. 371-380, 2015.
49. M. J. Gastinger, A. J. Barber, S. A. Khin, C. S. McRill, T. W. Gardner, and D. W. Marshak, "Abnormal centrifugal axons in streptozotocin-diabetic rat retinas, " Investigative Ophthalmology and Visual Science, vol. 42, no. 11, pp. 2679-2685, 2001.
50. M. J. Gastinger, A. R. Kunselman, E. E. Conboy, S. K. Bronson, and A. J. Barber, "Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2Akita diabetic mice, " Investigative Ophthalmology and Visual Science, vol. 49, no. 6, pp. 2635-2642, 2008.
51. J. R. Wolter, "Diabetic retinopathy, " American Journal of Ophthalmology, vol. 51, no. 5, pp. 1123-1141, 1961.
52. D. C. Fernandez, L. A. Pasquini, D. Dorfman, H. J. Aldana Marcos, and R. E. Rosenstein, "Early distal axonopathy of the visual pathway in experimental diabetes, " The American Journal of Pathology, vol. 180, no. 1, pp. 303-313, 2012.
53. L. Zhang, M. Inoue, K. Dong, and M. Yamamoto, "Alterations in retrograde axonal transport in optic nerve of type I and type II diabetic rats, " Kobe Journal of Medical Sciences, vol. 44, no. 5-6, pp. 205-215, 1998.
54. S. Bonnin, R. Tadayoni, A. Erginay, P. Massin, and B. Dupas, "Correlation between ganglion cell layer thinning and poor visual function after resolution of diabetic macular edema, " Investigative Ophthalmology and Visual Science, vol. 56, no. 2, pp. 978-982, 2015.
55. B. V. Bui, M. Loeliger, M. Thomas et al., "Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats, " Experimental Eye Research, vol. 88, no. 6, pp. 1076-1083, 2009.
56. J. A. Phipps, E. L. Fletcher, and A. J. Vingrys, "Paired-flash identification of rod and cone dysfunction in the diabetic rat, " Investigative Ophthalmology and Visual Science, vol. 45, no. 12, pp. 4592-4600, 2004.
57. Q. Li, E. Zemel, B. Miller, and I. Perlman, "Early retinal damage in experimental diabetes: electroretinographical and morphological observations, " Experimental Eye Research, vol. 74, no. 5, pp. 615-625, 2002.
58. D. Yonemura, T. Aoki, and K. Tsuzuki, "Electroretinogram in diabetic retinopathy, " Archives ofOphthalmology, vol. 68, pp. 19-24, 1962.
59. M. A. Bearse Jr., A. J. Adams, Y. Han et al., "A multifocal electroretinogram model predicting the development of diabetic retinopathy, " Progress in Retinal and Eye Research, vol. 25, no. 5, pp. 425-448, 2006.
60. G. H. Bresnick and M. Palta, "Oscillatory potential amplitudes. Relation to severity of diabetic retinopathy, " Archives of Ophthalmology, vol. 105, no. 7, pp. 929-933, 1987.
61. E. Lakhani, T. Wright, M. Abdolell, and C. Westall, "Multifocal ERG defects associated with insufficient long-term glycemic control in adolescents with type 1 diabetes, " Investigative Ophthalmology and Visual Science, vol. 51, no. 10, pp. 5297-5303, 2010.
62. M. McFarlane, T. Wright, D. Stephens, J. Nilsson, and C. A. Westall, "Blue flash ERG PhNR changes associated with poor long-termglycemic control in adolescents with type 1 diabetes, " Investigative Ophthalmology and Visual Science, vol. 53, no. 2, pp. 741-748, 2012.
63. K. Holopigian, W. Seiple, M. Lorenzo, and R. Carr, "A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy, " Investigative Ophthalmology and Visual Science, vol. 33, no. 10, pp. 2773-2780, 1992.
64. B. E. Wolff, M. A. Bearse, M. E. Schneck et al., "Color vision and neuroretinal function in diabetes, " Documenta Ophthalmologica, vol. 130, no. 2, pp. 131-139, 2015.
65. L. C. O. Andrade, G. S. Souza, E. M. C. B. Lacerda et al., "Influence of retinopathy on the achromatic and chromatic vision of patients with type 2 diabetes, " BMC Ophthalmology, vol. 14, article 104, pp. 1471-2415, 2014.
66. R. Simó and C. Hernández, "Neurodegeneration is an early event in diabetic retinopathy: therapeutic implications, " British Journal of Ophthalmology, vol. 96, no. 10, pp. 1285-1290, 2012.
67. A. Reis, C. Mateus, P. Melo, J. Figueira, J. Cunha-Vaz, and M. Castelo-Branco, "Neuroretinal dysfunction with intact bloodretinal barrier and absent vasculopathy in type 1 diabetes, " Diabetes, vol. 63, no. 11, pp. 3926-3937, 2014.
68. W. Tan, T. Wright, A. Dupuis, E. Lakhani, and C. Westall, "Localizing functional damage in the neural retina of adolescents and young adults with type 1 diabetes, " Investigative Ophthalmology and Visual Science, vol. 55, no. 4, pp. 2432-2441, 2014.
69. M. Chen, T. M. Curtis, and A. W. Stitt, "Advanced glycation end products and diabetic retinopathy, " Current Medicinal Chemistry, vol. 20, no. 26, pp. 3234-3240, 2013.
70. H. Zong, M. Ward, and A. W. Stitt, "AGEs, RAGE, and diabetic retinopathy, " Current Diabetes Reports, vol. 11, no. 4, pp. 244-252, 2011.
71. B.-H. Chen, D.-Y. Jiang, and L.-S. Tang, "Advanced glycation end-products induce apoptosis involving the signaling pathways of oxidative stress in bovine retinal pericytes, " Life Sciences, vol. 79, no. 11, pp. 1040-1048, 2006.
72. B. Liu, M. Bhat, A. K. Padival, D. G. Smith, and R. H. Nagaraj, "Effect of dicarbonyl modification of fibronectin on retinal capillary pericytes, " Investigative Ophthalmology and Visual Science, vol. 45, no. 6, pp. 1983-1995, 2004.
73. R. Chibber, P. A. Molinatti, N. Rosatto, B. Lambourne, and E. M. Kohner, "Toxic action of advanced glycation end products on cultured retinal capillary pericytes and endothelial cells: relevance to diabetic retinopathy, " Diabetologia, vol. 40, no. 2, pp. 156-164, 1997.
74. A. W. Stitt, C. McGoldrick, A. Rice-McCaldin et al., "Impaired retinal angiogenesis in diabetes: role of advanced glycation end products and galectin-3, " Diabetes, vol. 54, no. 3, pp. 785-794, 2005.
75. M. Nitti, A. L. Furfaro, N. Traverso et al., "PKC delta and NADPH oxidase in AGE-induced neuronal death, " Neuroscience Letters, vol. 416, no. 3, pp. 261-265, 2007.
76. H. Zong, M. Ward, A. Madden et al., "Hyperglycaemia-induced pro-inflammatory responses by retinalMüller glia are regulated by the receptor for advanced glycation end-products (RAGE), " Diabetologia, vol. 53, no. 12, pp. 2656-2666, 2010.
77. J. Kim, C.-S. Kim, Y. M. Lee, E. Sohn, K. Jo, and J. S. Kim, "Litsea japonica extract inhibits neuronal apoptosis and the accumulation of advanced glycation end products in the diabetic mouse retina, " Molecular Medicine Reports, vol. 12, no. 1, pp. 1075-1081, 2015.
78. J. Kim, C.-S. Kim, E. Sohn et al., "Aminoguanidine protects against apoptosis of retinal ganglion cells in Zucker diabetic fatty rats, " European Review for Medical and Pharmacological Sciences, vol. 18, no. 11, pp. 1573-1578, 2014.
79. A. Lecleire-Collet, L. H. Tessier, P. Massin et al., "Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants, " British Journal of Ophthalmology, vol. 89, no. 12, pp. 1631-1633, 2005.
80. F. Reber, R. Geffarth, M. Kasper et al., "Graded sensitiveness of the various retinal neuron populations on the glyoxal-mediated formation of advanced glycation end products and ways of protection, " Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 241, no. 3, pp. 213-225, 2003.
81. M. Dal Monte, R. Amato, M. Biagioni, M. Cammalleri, and G. Casini, "Neuroprotection as a therapeutic target in diabetic retinopathy: a basic approach, " Acta Ophthalmologica, vol. 93, supplement S255, 2015.
82. E. Lieth, A. J. Barber, B. Xu et al., "Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group, " Diabetes, vol. 47, no. 5, pp. 815-820, 1998.
83. E. Lieth, K. F. LaNoue, D. A. Antonetti, M. Ratz, and The Penn State Retina ResearchGroup, "Diabetes reduces glutamate oxidation and glutamine synthesis in the retina, " Experimental Eye Research, vol. 70, no. 6, pp. 723-730, 2000.
84. R. A. Kowluru, R. L. Engerman, G. L. Case, and T. S. Kern, "Retinal glutamate in diabetes and effect of antioxidants, " Neurochemistry International, vol. 38, no. 5, pp. 385-390, 2001.
85. Y.-K. Ng, X.-X. Zeng, and E.-A. Ling, "Expression of glutamate receptors and calcium-binding proteins in the retina of streptozotocin-induced diabetic rats, " Brain Research, vol. 1018, no. 1, pp. 66-72, 2004.
86. A. F. Castilho, J. T. Liberal, F. I. Baptista, J. M. Gaspar, A. L. Carvalho, and A. F. Ambrósio, "Elevated glucose concentration changes the content and cellular localization ofAMPAreceptors in the retina but not in the hippocampus, " Neuroscience, vol. 219, pp. 23-32, 2012.
87. A. R. Santiago, S. C. Rosa, P. F. Santos, A. J. Cristóvão, A. J. Barber, and A. F. Ambrósio, "Elevated glucose changes the expression of ionotropic glutamate receptor subunits and impairs calcium homeostasis in retinal neural cells, " Investigative Ophthalmology and Visual Science, vol. 47, no. 9, pp. 4130-4137, 2006.
88. A. R. Santiago, J. M. Gaspar, F. I. Baptista et al., "Diabetes changes the levels of ionotropic glutamate receptors in the rat retina, " Molecular Vision, vol. 15, pp. 1620-1630, 2009.
89. J. Ambati, K. V. Chalam, D. K. Chawala et al., "Elevated-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patientswith proliferative diabetic retinopathy, " Archives of Ophthalmology, vol. 115, no. 9, pp. 1161-1166, 1997.
90. M.-J. Lu, J. S. Pulido, C. A. McCannel et al., "Detection of elevated signaling amino acids in human diabetic vitreous by rapid capillary electrophoresis, " Experimental Diabesity Research, vol. 2007, Article ID 39765, 6 pages, 2007.
91. A. R. Santiago, J. M. Hughes, W. Kamphuis, R. O. Schlingemann, and A. F. Ambrósio, "Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina, " Brain Research, vol. 1198, pp. 153-159, 2008.
92. Q. Li and D. G. Puro, "Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells, " Investigative Ophthalmology and Visual Science, vol. 43, no. 9, pp. 3109-3116, 2002.
93. K. H. Gabbay, "The sorbitol pathway and the complications of diabetes, "The New England Journal ofMedicine, vol. 288, no. 16, pp. 831-836, 1973.
94. I. G. Obrosova and P. F. Kador, "Aldose reductase/polyol inhibitors for diabetic retinopathy, " Current Pharmaceutical Biotechnology, vol. 12, no. 3, pp. 373-385, 2011.
95. Z. Dagher, Y. S. Park, V. Asnaghi, T. Hoehn, C. Gerhardinger, and M. Lorenzi, "Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy, " Diabetes, vol. 53, no. 9, pp. 2404-2411, 2004.
96. C. A. Lee, G. Li, M. D. Patel et al., "Diabetes-induced impairment in visual function in mice: contributions of p38 MAPK, RAGE, leukocytes, and aldose reductase, " Investigative Ophthalmology and Visual Science, vol. 55, no. 5, pp. 2904-2910, 2014.
97. M. Lorenzi, "The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient, " Experimental Diabetes Research, vol. 2007, Article ID 61038, 10 pages, 2007.
98. V. R. Drel, W. Xu, J. Zhang et al., "Poly(ADP-ribose)polymerase inhibition counteracts cataract formation and early retinal changes in streptozotocin-diabetic rats, " Investigative Ophthalmology and Visual Science, vol. 50, no. 4, pp. 1778-1790, 2009.
99. L. Zheng, C. Szabó, and T. S. Kern, "Poly(ADP-ribose) polymerase is involved in the development of diabetic retinopathy via regulation of nuclear factor-B, " Diabetes, vol. 53, no. 11, pp. 2960-2967, 2004.
100. I. G. Obrosova and U. A. Julius, "Role for poly(ADP-ribose) polymerase activation in diabetic nephropathy, neuropathy and retinopathy, " Current Vascular Pharmacology, vol. 3, no. 3, pp. 267-283, 2005.
101. G. Mohammad, M. M. Siddiquei, and A. M. Abu El-Asrar, "Poly (ADP-Ribose) polymerase mediates diabetes-induced retinal neuropathy, " Mediators of Inflammation, vol. 2013, Article ID 510451, 10 pages, 2013.
102. S. Z. Safi, R. Qvist, S. Kumar, K. Batumalaie, and I. S. B. Ismail, "Molecularmechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets, " BioMed Research International, vol. 2014, Article ID 801269, 18 pages, 2014.
103. M. Nakamura, A. J. Barber, D. A. Antonetti et al., "Excessive hexosamines block the neuroprotective effect of insulin and induce apoptosis in retinal neurons, " The Journal of Biological Chemistry, vol. 276, no. 47, pp. 43748-43755, 2001.
104. T. E. Fox, M. M. Young, M. M. Pedersen, S. Giambuzzi-Tussey, M. Kester, and T. W. Gardner, "Insulin signaling in retinal neurons is regulated within cholesterol-enriched membrane microdomains, " American Journal of Physiology-Endocrinology and Metabolism, vol. 300, no. 3, pp. E600-E609, 2011.
105. T. Behl, I. Kaur, and A. Kotwani, "Implication of oxidative stress in progression of diabetic retinopathy, " Survey of Ophthalmology, vol. 61, no. 2, pp. 187-196, 2016.
106. D. M. van Reyk, M. C. Gillies, and M. J. Davies, "The retina: oxidative stress and diabetes, " Redox Report, vol. 8, no. 4, pp. 187-192, 2003.
107. M. Sasaki, Y. Ozawa, T. Kurihara et al., "Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes, " Diabetologia, vol. 53, no. 5, pp. 971-979, 2010.
108. L. Zheng and T. S. Kern, "Role of nitric oxide, superoxide, peroxynitrite and PARP in diabetic retinopathy, " Frontiers in Bioscience, vol. 14, no. 10, pp. 3974-3987, 2009.
109. R. A. Kowluru, "Diabetes-induced elevations in retinal oxidative stress, protein kinase C and nitric oxide are interrelated, " Acta Diabetologica, vol. 38, no. 4, pp. 179-185, 2001.
110. M. Coucha, S. L. Elshaer, W. S. Eldahshan, B. A. Mysona, and A. B. El-Remessy, "Molecularmechanisms of diabetic retinopathy: potential therapeutic targets, " Middle East African Journal of Ophthalmology, vol. 22, no. 2, pp. 135-144, 2015.
111. C. Piperi, A. Goumenos, C. Adamopoulos, and A. G. Papavassiliou, "AGE/RAGE signalling regulation by miRNAs: associations with diabetic complications and therapeutic potential, " International Journal of Biochemistry and Cell Biology, vol. 60, pp. 197-201, 2015.
112. M. J. Giese and R. C. Speth, "The ocular renin-angiotensin system: a therapeutic target for the treatment of ocular disease, " Pharmacology andTherapeutics, vol. 142, no. 1, pp. 11-32, 2014.
113. J. L. Wilkinson-Berka, "Angiotensin and diabetic retinopathy, " International Journal of Biochemistry and Cell Biology, vol. 38, no. 5-6, pp. 752-765, 2006.
114. J. L. Wilkinson-Berka, A. Agrotis, and D. Deliyanti, "The retinal renin-angiotensin system: roles of angiotensin II and aldosterone, " Peptides, vol. 36, no. 1, pp. 142-150, 2012.
115. B. V. Bui, J. A. Armitage, M. Tolcos, M. E. Cooper, and A. J. Vingrys, "ACE inhibition salvages the visual loss caused by diabetes, " Diabetologia, vol. 46, no. 3, pp. 401-408, 2003.
116. T. Kurihara, Y. Ozawa, N. Nagai et al., "Angiotensin II type 1 receptor signaling contributes to synaptophysin degradation and neuronal dysfunction in the diabetic retina, " Diabetes, vol. 57, no. 8, pp. 2191-2198, 2008.
117. T. Sugiyama, T. Okuno, M. Fukuhara et al., "Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type 2 diabetes, " Experimental Eye Research, vol. 85, no. 3, pp. 406-412, 2007.
118. K. C. Silva, M. A. B. Rosales, S. K. Biswas, J. B. L. De Faria, and J. M. L. De Faria, "Diabetic retinal neurodegeneration is associated with mitochondrial oxidative stress and is improved by an angiotensin receptor blocker in a model combining hypertension and diabetes, " Diabetes, vol. 58, no. 6, pp. 1382-1390, 2009.
119. A. M. Joussen, V. Poulaki, M. L. Le et al., "A central role for inflammation in the pathogenesis of diabetic retinopathy, " The FASEB Journal, vol. 18, no. 12, pp. 1450-1452, 2004.
120. Y. Yu, H. Chen, and S. B. Su, "Neuroinflammatory responses in diabetic retinopathy, " Journal of Neuroinflammation, vol. 12, article 141, 2015.
121. S. B. Beynon and F. R. Walker, "Microglial activation in the injured and healthy brain: what are we really talking about? Practical and theoretical issues associated with the measurement of changes in microglial morphology, " Neuroscience, vol. 225, pp. 162-171, 2012.
122. E. Polazzi and B. Monti, "Microglia and neuroprotection: from in vitro studies to therapeutic applications, " Progress in Neurobiology, vol. 92, no. 3, pp. 293-315, 2010.
123. M. Mizutani, C. Gerhardinger, and M. Lorenzi, "Muller cell changes in human diabetic retinopathy, " Diabetes, vol. 47, no. 3, pp. 445-449, 1998.
124. X. Liu, F. Ye, H. Xiong et al., "IL-1 Induces IL-6 production in retinalMüller cells predominantly through the activation of P38 MAPK/NF-B signaling pathway, " Experimental Cell Research, vol. 331, no. 1, pp. 223-231, 2015.
125. C. Gerhardinger, M. B. Costa, M. C. Coulombe, I. Toth, T. Hoehn, and P. Grosu, "Expression of acute-phase response proteins in retinal Muller cells in diabetes, " Investigative Ophthalmology and Visual Science, vol. 46, no. 1, pp. 349-357, 2005.
126. T. C. Frank-Cannon, L. T. Alto, F. E. McAlpine, and M. G. Tansey, "Does neuroinflammation fan the flame in neurodegenerative diseases?" Molecular Neurodegeneration, vol. 4, article 47, pp. 1750-1326, 2009.
127. M. E. Lull and M. L. Block, "Microglial activation and chronic neurodegeneration, " Neurotherapeutics, vol. 7, no. 4, pp. 354-365, 2010.
128. S. X. Zhang, E. Sanders, S. J. Fliesler, and J. J. Wang, "Endoplasmic reticulum stress and the unfolded protein responses in retinal degeneration, " Experimental Eye Research, vol. 125, pp. 30-40, 2014.
129. M. Shimazawa, A. Miwa, Y. Ito, K. Tsuruma, M. Aihara, and H. Hara, "Involvement of endoplasmic reticulumstress in optic nerve degeneration following N-methyl-D-aspartate-induced retinal damage in mice, " Journal of Neuroscience Research, vol. 90, no. 10, pp. 1960-1969, 2012.
130. L. P. Yang, L. M. Wu, D. M. Wang et al., "Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy, " Neural Regeneration Research, vol. 8, no. 33, pp. 3148-3158, 2013.
131. C. E. N. Reiter, L. Sandirasegarane, E. B. Wolpert et al., "Characterization of insulin signaling in rat retina in vivo and ex vivo, " American Journal of Physiology-Endocrinology and Metabolism, vol. 285, no. 4, pp. E763-E774, 2003.
132. X. Wu, C. E. N. Reiter, D. A. Antonetti, S. R. Kimball, L. S. Jefferson, and T. W. Gardner, "Insulin promotes rat retinal neuronal cell survival in a p70S6K-dependent manner, " Journal of Biological Chemistry, vol. 279, no. 10, pp. 9167-9175, 2004.
133. A. J. Barber, M. Nakamura, E. B. Wolpert et al., "Insulin rescues retinal neurons from apoptosis by a phosphatidylinositol 3-kinase/Akt-mediated mechanism that reduces the activation of caspase-3, " Journal of Biological Chemistry, vol. 276, no. 35, pp. 32814-32821, 2001.
134. C. E. N. Reiter, X. Wu, L. Sandirasegarane et al., "Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin, " Diabetes, vol. 55, no. 4, pp. 1148-1156, 2006.
135. C. Gerhardinger, K. D. McClure, G. Romeo, F. Podestà, and M. Lorenzi, "IGF-I mRNA and signaling in the diabetic retina, " Diabetes, vol. 50, no. 1, pp. 175-183, 2001.
136. A. Kummer, B. E. Pulford, D. N. Ishii, andG. M. Seigel, "Des(1-3)IGF-1 treatment normalizes type 1 IGF receptor and phospho-Akt (Thr 308) immunoreactivity in predegenerative retina of diabetic rats, " Experimental Diabesity Research, vol. 4, no. 1, pp. 45-57, 2003.
137. C. J. Barnstable and J. Tombran-Tink, "Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential, " Progress in Retinal and Eye Research, vol. 23, no. 5, pp. 561-577, 2004.
138. B. Zheng, T. Li, H. Chen, X. Xu, and Z. Zheng, "Correlation between ficolin-3 and vascular endothelial growth factor-topigment epithelium-derived factor ratio in the vitreous of eyes with proliferative diabetic retinopathy, " American Journal of Ophthalmology, vol. 152, no. 6, pp. 1039-1043, 2011.
139. X. Shen, Y. Zhong, B. Xie, Y. Cheng, and Q. Jiao, "Pigment epithelium derived factor as an anti-inflammatory factor against decrease of glutamine synthetase expression in retinal Müller cells under high glucose conditions, " Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 248, no. 8, pp. 1127-1136, 2010.
140. B. Xie, Q. Jiao, Y. Cheng, Y. Zhong, and X. Shen, "Effect of pigment epithelium-derived factor on glutamate uptake in retinal Müller cells under high-glucose conditions, " Investigative Ophthalmology and Visual Science, vol. 53, no. 2, pp. 1023-1032, 2012.
141. A. M. Abu El-Asrar, G. Mohammad, G. De Hertogh et al., "Neurotrophins and neurotrophin receptors in proliferative diabetic retinopathy, " PLoSONE, vol. 8, no. 6, Article IDe65472, 2013.
142. M. M. H. Al-Gayyar, S. Matragoon, B. A. Pillai, T. K. Ali, M. A. Abdelsaid, and A. B. El-Remessy, "Epicatechin blocks pro-nerve growth factor (proNGF)-mediated retinal neurodegeneration via inhibition of p75 neurotrophin receptor proNGF expression in a rat model of diabetes, " Diabetologia, vol. 54, no. 3, pp. 669-680, 2011.
143. B. A. Mysona, M. M. H. Al-Gayyar, S. Matragoon et al., "Modulation of p75NTR prevents diabetes-and proNGF-induced retinal inflammation and blood-retina barrier breakdown in mice and rats, " Diabetologia, vol. 56, no. 10, pp. 2329-2339, 2013.
144. B. A. Mysona, A. Y. Shanab, S. L. Elshaer, and A. B. El-Remessy, "Nerve growth factor in diabetic retinopathy: beyond neurons, " Expert Review of Ophthalmology, vol. 9, no. 2, pp. 99-107, 2014.
145. M. S. Ola, M. I. Nawaz, A. A. El-Asrar, M. Abouammoh, and A. S. Alhomida, "Reduced levels of brain derived neurotrophic factor (BDNF) in the serum of diabetic retinopathy patients and in the retina of diabetic rats, " Cellular and Molecular Neurobiology, vol. 33, no. 3, pp. 359-367, 2013.
146. G. I. Liou, Y. Fei, N. S. Peachey et al., "Early onset photoreceptor abnormalities induced by targeted disruption of the interphotoreceptor retinoid-binding protein gene, " Journal of Neuroscience, vol. 18, no. 12, pp. 4511-4520, 1998.
147. M. Garciá-Ramírez, F. Canals, C. Hernández et al., "Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy, " Diabetologia, vol. 50, no. 6, pp. 1294-1303, 2007.
148. M. Garcia-Ramírez, C. Hernández, M. Villarroel et al., "Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy, " Diabetologia, vol. 52, no. 12, pp. 2633-2641, 2009.
149. G. Casini, E. Catalani, M. Dal Monte, and P. Bagnoli, "Functional aspects of the somatostatinergic system in the retina and the potential therapeutic role of somatostatin in retinal disease, " Histology and Histopathology, vol. 20, no. 2, pp. 615-632, 2005.
150. E. Carrasco, C. Hernández, A. Miralles, P. Huguet, J. Farrés, and R. Simó, "Lower somatostatin expression is an early event in diabetic retinopathy and is associated with retinal neurodegeneration, " Diabetes Care, vol. 30, no. 11, pp. 2902-2908, 2007.
151. C. Hernández, E. Carrasco, R. Casamitjana, R. Deulofeu, J. Garciá-Arumí, and R. Simó, "Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects, " Diabetes Care, vol. 28, no. 8, pp. 1941-1947, 2005.
152. R. Simó, A. Lecube, L. Sararols et al., "Deficit of somatostatinlike immunoreactivity in the vitreous fluid of diabetic patients: possible role in the development of proliferative diabetic retinopathy, " Diabetes Care, vol. 25, no. 12, pp. 2282-2286, 2002.
153. R. Simó, E. Carrasco, A. Fonollosa, J. Garciá-Arumí, R. Casamitjana, and C. Hernández, "Deficit of somatostatin in the vitreous fluid of patients with diabetic macular edema, " Diabetes Care, vol. 30, no. 3, pp. 725-727, 2007.
154. E. Catalani, D. Cervia, D. Martini et al., "Changes in neuronal response to ischemia in retinas with genetic alterations of somatostatin receptor expression, " European Journal of Neuroscience, vol. 25, no. 5, pp. 1447-1459, 2007.
155. D. Cervia, D. Martini, C. Ristori et al., "Modulation of the neuronal response to ischaemia by somatostatin analogues in wildtype and knock-out mouse retinas, " Journal of Neurochemistry, vol. 106, no. 5, pp. 2224-2235, 2008.
156. A. D'Alessandro, D. Cervia, E. Catalani, F. Gevi, L. Zolla, and G. Casini, "Protective effects of the neuropeptides PACAP, substance P and the somatostatin analogue octreotide in retinal ischemia: a metabolomic analysis, " Molecular BioSystems, vol. 10, no. 6, pp. 1290-1304, 2014.
157. C. Hernández, M. Garciá-Ramírez, L. Corraliza et al., "Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes, " Diabetes, vol. 62, no. 7, pp. 2569-2578, 2013.
158. C. Iadecola and J. Anrather, "Stroke research at a crossroad: asking the brain for directions, " Nature Neuroscience, vol. 14, no. 11, pp. 1363-1368, 2011.
159. D. Cervia, E. Catalani, M. Dal Monte, andG. Casini, "Vascular endothelial growth factor in the ischemic retina and its regulation by somatostatin, " Journal of Neurochemistry, vol. 120, no. 5, pp. 818-829, 2012.
160. A. R. Cervantes-Villagrana, J. Garcia-Román, C. Gonzlez-Espinosa, and M. Lamas, "Pharmacological inhibition of nmethyl d-aspartate receptor promotes secretion of vascular endothelial growth factor in müller cells: effects of hyperglycemia and hypoxia, " Current Eye Research, vol. 35, no. 8, pp. 733-741, 2010.
161. J. Kusari, S. X. Zhou, E. Padillo, K. G. Clarke, and D. W. Gil, "Inhibition of vitreoretinal VEGF elevation and blood-retinal barrier breakdown in streptozotocin-induced diabetic rats by brimonidine, " Investigative Ophthalmology and Visual Science, vol. 51, no. 2, pp. 1044-1051, 2010.
162. A. Ebneter, G. Chidlow, J. P. M. Wood, and R. J. Casson, "Protection of retinal ganglion cells and the optic nerve during short-term hyperglycemia in experimental glaucoma, " Archives of Ophthalmology, vol. 129, no. 10, pp. 1337-1344, 2011.
163. M. Saint-Geniez, A. S. R. Maharaj, T. E. Walshe et al., "Endogenous VEGF is required for visual function: evidence for a survival role on Müller cells and photoreceptors, " PLoS ONE, vol. 3, no. 11, Article ID e3554, 2008.
164. R. H. Foxton, A. Finkelstein, S. Vijay et al., "VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma, " The American Journal of Pathology, vol. 182, no. 4, pp. 1379-1390, 2013.
165. M. R. Romano, F. Biagioni, G. Besozzi et al., "Effects of bevacizumab on neuronal viability of retinal ganglion cells in rats, " Brain Research, vol. 1478, pp. 55-63, 2012.
166. M. Azzouz, G. S. Ralph, E. Storkebaum et al., "VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model, " Nature, vol. 429, no. 6990, pp. 413-417, 2004.
167. G. Casini, M. Dal Monte, I. Fornaciari, L. Filippi, and P. Bagnoli, "The-adrenergic system as a possible new target for pharmacologic treatment of neovascular retinal diseases, " Progress in Retinal and Eye Research, vol. 42, pp. 103-129, 2014.
168. M. A. Abdelsaid, B. A. Pillai, S. Matragoon, R. Prakash, M. Al-Shabrawey, and A. B. El-Remessy, "Early intervention of tyrosine nitration prevents vaso-obliteration and neovascularization in ischemic retinopathy, " Journal of Pharmacology and Experimental Therapeutics, vol. 332, no. 1, pp. 125-134, 2010.
169. A. B. El-Remessy, M. Bartoli, D. H. Platt, D. Fulton, and R. B. Caldwell, "Oxidative stress inactivates VEGF survival signaling in retinal endothelial cells via PI 3-kinase tyrosine nitration, " Journal of Cell Science, vol. 118, no. 1, pp. 243-252, 2005.
170. N. Beazley-Long, J. Hua, T. Jehle et al., "VEGF-A165b is an endogenous neuroprotective splice isoform of vascular endothelial growth factor a in vivo and in vitro, " The American Journal of Pathology, vol. 183, no. 3, pp. 918-929, 2013.
171. R. M. Perrin, O. Konopatskaya, Y. Qiu, S. Harper, D. O. Bates, and A. J. Churchill, "Diabetic retinopathy is associated with a switch in splicing from anti-to pro-angiogenic isoforms of vascular endothelial growth factor, " Diabetologia, vol. 48, no. 11, pp. 2422-2427, 2005.
172. J. S. Ng, M. A. Bearse Jr., M. E. Schneck, S. Barez, and A. J. Adams, "Local diabetic retinopathy prediction by multifocal ERG delays over 3 years, " Investigative Ophthalmology and Visual Science, vol. 49, no. 4, pp. 1622-1628, 2008.
173. Y. Han, M. E. Schneck, M. A. Bearse Jr. et al., "Formulation and evaluation of a predictive model to identify the sites of future diabetic retinopathy, " Investigative Ophthalmology and Visual Science, vol. 45, no. 11, pp. 4106-4112, 2004.
174. W. W. Harrison, M. A. Bearse Jr., J. S. Ng et al., "Multifocal electroretinograms predict onset of diabetic retinopathy in adult patients with diabetes, " Investigative Ophthalmology and Visual Science, vol. 52, no. 2, pp. 772-777, 2011.
175. S. Vujosevic, S. Bini, G. Midena, M. Berton, E. Pilotto, and E. Midena, "Hyperreflective intraretinal spots in diabetics without and with nonproliferative diabetic retinopathy: an in vivo study using spectral domain OCT, " Journal of Diabetes Research, vol. 2013, Article ID 491835, 5 pages, 2013.
176. M. G. Field, D. Yang, Z.-M. Bian, H. R. Petty, and V. M. Elner, "Retinal flavoprotein fluorescence correlates with mitochondrial stress, apoptosis, and chemokine expression, " Experimental Eye Research, vol. 93, no. 4, pp. 548-555, 2011.
177. M. G. Field, V. M. Elner, D. G. Puro et al., "Rapid, noninvasive detection of diabetes-induced retinal metabolic stress, " Archives of Ophthalmology, vol. 126, no. 7, pp. 934-938, 2008.
178. L. P. Aiello, "Targeting intraocular neovascularization and edema-one drop at a time, " The New England Journal of Medicine, vol. 359, no. 9, pp. 967-969, 2008.
179. M. DalMonte, G. Casini, G. laMarca, B. Isacchi, L. Filippi, and P. Bagnoli, "Eye drop propranolol administration promotes the recovery of oxygen-induced retinopathy in mice, " Experimental Eye Research, vol. 111, pp. 27-35, 2013.
180. A. Lambiase, F. Mantelli, and S. Bonini, "Nerve growth factor eye drops to treat glaucoma, " Drug News and Perspectives, vol. 23, no. 6, pp. 361-367, 2010.
181. M. Saylor, L. K. McLoon, A. R. Harrison, and M. S. Lee, "Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review, " Archives of Ophthalmology, vol. 127, no. 4, pp. 402-406, 2009.
182. N. Cheung, P. Mitchell, and T. Y. Wong, "Diabetic retinopathy, " The Lancet, vol. 376, no. 9735, pp. 124-136, 2010.
183. A. Robin and D. S. Grover, "Compliance and adherence in glaucoma management, " Indian Journal of Ophthalmology, vol. 59, supplement 1, pp. S93-S96, 2011.
184. P. E. Fort, M. K. Losiewicz, C. E. N. Reiter et al., "Differential roles of hyperglycemia and hypoinsulinemia in diabetes induced retinal cell death: evidence for retinal insulin resistance, " PLoS ONE, vol. 6, no. 10, Article IDe26498, 2011.
185. G. P. Misra, R. S. J. Singh, T. S. Aleman, S. G. Jacobson, T. W. Gardner, and T. L. Lowe, "Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina, " Biomaterials, vol. 30, no. 33, pp. 6541-6547, 2009.
186. F. Polato and S. P. Becerra, "Pigment epithelium-derived factor, a protective factor for photoreceptors in Vivo, " Advances in ExperimentalMedicine and Biology, vol. 854, pp. 699-706, 2016.
187. Y. Yoshida, S.-I. Yamagishi, T. Matsui et al., "Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy, " Diabetes/Metabolism Research and Reviews, vol. 25, no. 7, pp. 678-686, 2009.
188. J. Tombran-Tink, "PEDF in angiogenic eye diseases, " Current Molecular Medicine, vol. 10, no. 3, pp. 267-278, 2010.
189. H. Liu, J.-G. Ren, W. L. Cooper, C. E. Hawkins, M. R. Cowan, and P. Y. Tong, "Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 17, pp. 6605-6610, 2004.
190. M. Elahy, S. Baindur-Hudson, V. F. Cruzat, P. Newsholme, and C. R. Dass, "Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy, " Journal of Endocrinology, vol. 222, no. 3, pp. R129-R139, 2014.
191. Y. Wang, Q. Lu, S. Gao et al., "Pigment epithelium-derived factor regulates glutamine synthetase and l-glutamate/l-aspartate transporter in retinas with oxygen-induced retinopathy, " Current Eye Research, vol. 40, no. 12, pp. 1232-1244, 2015.
192. R. Longeras, K. Farjo, M. Ihnat, and J.-X. Ma, "A PEDFderived peptide inhibits retinal neovascularization and blocks mobilization of bone marrow-derived endothelial progenitor cells, " Experimental Diabetes Research, vol. 2012, Article ID 518426, 11 pages, 2012.
193. Y. Liu, L. F. Leo, C. McGregor, A. Grivitishvili, C. J. Barnstable, and J. Tombran-Tink, "Pigment epithelium-derived factor (PEDF) peptide eye drops reduce inflammation, cell death and vascular leakage in diabetic retinopathy in Ins2Akita mice, " Molecular Medicine, vol. 18, pp. 1387-1401, 2012.
194. V. Vigneswara, M. Esmaeili, L. Deer, M. Berry, A. Logan, and Z. Ahmed, "Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration, " Molecular and Cellular Neuroscience, vol. 68, pp. 212-221, 2015.
195. D. Cervia and G. Casini, "The neuropeptide systems and their potential role in the treatment of mammalian retinal ischemia: a developing story, " Current Neuropharmacology, vol. 11, no. 1, pp. 95-101, 2013.
196. M. Dal Monte, C. Petrucci, A. Cozzi, J. P. Allen, and P. Bagnoli, "Somatostatin inhibits potassium-evoked glutamate release by activation of the sst2 somatostatin receptor in the mouse retina, " Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 367, no. 2, pp. 188-192, 2003.
197. T. Atlasz, K. Szabadfi, P. Kiss et al., "Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects, " Annals of the New York Academy of Sciences, vol. 1200, pp. 128-139, 2010.
198. T. Seki, H. Itoh, T. Nakamachi et al., "Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure, " Journal of Molecular Neuroscience, vol. 43, no. 1, pp. 30-34, 2011.
199. C. Hlscher, "Potential role of glucagon-like peptide-1 (GLP-1) in neuroprotection, " CNS Drugs, vol. 26, no. 10, pp. 871-882, 2012.
200. Y. Zhang, J. Zhang, Q. Wang et al., "Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats, " Investigative Ophthalmology and Visual Science, vol. 52, no. 1, pp. 278-285, 2011.
201. Y. Fan, K. Liu, Q. Wang, Y. Ruan, Y. Zhang, andW. Ye, "Exendin-4 protects retinal cells fromearly diabetes in Goto-Kakizaki rats by increasing the Bcl-2/Bax and Bcl-xL/Bax ratios and reducing reactive gliosis, " Molecular Vision, vol. 20, pp. 1557-1568, 2014.
202. C. Hernandez, P. Bogdanov, L. Corraliza et al., "Topical administration of GLP-1 receptor agonists prevents retinal neurodegeneration in experimental diabetes, " Diabetes, vol. 65, no. 1, pp. 172-187, 2016.
203. Y. Gong, Z.-P. Chang, R.-T. Ren et al., "Protective effects of adeno-associated virus mediated brain-derived neurotrophic factor expression on retinal ganglion cells in diabetic rats, " Cellular andMolecular Neurobiology, vol. 32, no. 3, pp. 467-475, 2012.
204. B.-A. Berk, S. Vogler, T. Pannicke et al., "Brain-derived neurotrophic factor inhibits osmotic swelling of rat retinal glial (Müller) and bipolar cells by activation of basic fibroblast growth factor signaling, " Neuroscience, vol. 295, pp. 175-186, 2015.
205. H. P. Hammes, H. J. Federoff, and M. Brownlee, "Nerve growth factor prevents both neuroretinal programmed cell death and capillary pathology in experimental diabetes, " Molecular Medicine, vol. 1, no. 5, pp. 527-534, 1995.
206. V. Colafrancesco, M. Coassin, S. Rossi, and L. Aloe, "Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration, " Annali dell'Istituto Superiore di Sanita, vol. 47, no. 3, pp. 284-289, 2011.
207. S. Majumdar and R. Srirangam, "Potential of the bioflavonoids in the prevention/treatment of ocular disorders, " Journal of Pharmacy and Pharmacology, vol. 62, no. 8, pp. 951-965, 2010.
208. B. Kumar, S. K. Gupta, T. C. Nag et al., "Retinal neuroprotective effects of quercetin in streptozotocin-induced diabetic rats, " Experimental Eye Research, vol. 125, pp. 193-202, 2014.
209. F. Ghadiri Soufi, E. Arbabi-Aval, M. Rezaei Kanavi, and H. Ahmadieh, "Anti-inflammatory properties of resveratrol in the retinas of type 2 diabetic rats, " Clinical and Experimental Pharmacology and Physiology, vol. 42, no. 1, pp. 63-68, 2015.
210. F. G. Soufi, M. Vardyani, R. Sheervalilou, M. Mohammadi, and M. H. Somi, "Long-term treatment with resveratrol attenuates oxidative stress pro-inflammatory mediators and apoptosis in streptozotocin-nicotinamide-induced diabetic rats, " General Physiology and Biophysics, vol. 31, no. 4, pp. 431-438, 2012.
211. A. S. Yar, S. Menevse, I. Dogan et al., "Investigation of ocular neovascularization-related genes and oxidative stress in diabetic rat eye tissues after resveratrol treatment, " Journal of Medicinal Food, vol. 15, no. 4, pp. 391-398, 2012.
212. T. Mrudula, P. Suryanarayana, P. N. B. S. Srinivas, and G. B. Reddy, "Effect of curcumin on hyperglycemia-induced vascular endothelial growth factor expression in streptozotocin-induced diabetic rat retina, " Biochemical and Biophysical Research Communications, vol. 361, no. 2, pp. 528-532, 2007.
213. Z.-F. Zuo, Q. Zhang, and X.-Z. Liu, "Protective effects of curcumin on retinalMüller cell in early diabetic rats, " International Journal of Ophthalmology, vol. 6, no. 4, pp. 422-424, 2013.
214. S. K. Gupta, B. Kumar, T. C. Nag et al., "Curcumin prevents experimental diabetic retinopathy in rats through its hypoglycemic, antioxidant, and anti-inflammatory mechanisms, " Journal of Ocular Pharmacology and Therapeutics, vol. 27, no. 2, pp. 123-130, 2011.
215. B. Kumar, S. K. Gupta, B. P. Srinivasanet al., "Hesperetinrescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats, " Microvascular Research, vol. 87, pp. 65-74, 2013.
216. A. S. Ibrahim, M. M. El-Shishtawy, A. Peña Jr., and G. I. Liou, "Genistein attenuates retinal inflammation associated with diabetes by targeting of microglial activation, " Molecular Vision, vol. 16, pp. 2033-2042, 2010.
217. S. A. Elgayar, S. A. Eltony, A. A. Sayed, and M. M. Abdel-Rouf, "Genistein treatment confers protection against gliopathy and vasculopathy of the diabetic retina in rats, " Ultrastructural Pathology, vol. 39, no. 6, pp. 385-394, 2015.
218. M. Nebbioso, M. Federici, D. Rusciano, M. Evangelista, and N. Pescosolido, "Oxidative stress in preretinopathic diabetes subjects and antioxidants, " Diabetes Technology and Therapeutics, vol. 14, no. 3, pp. 257-263, 2012.
219. K. C. Silva, M. A. B. Rosales, D. E. Hamassaki et al., "Green tea is neuroprotective in diabetic retinopathy, " Investigative Ophthalmology and Visual Science, vol. 54, no. 2, pp. 1325-1336, 2013.
220. R. A. Kowluru, B. Menon, and D. L. Gierhart, "Beneficial effect of zeaxanthin on retinal metabolic abnormalities in diabetic rats, " InvestigativeOphthalmologyandVisual Science, vol. 49, no. 4, pp. 1645-1651, 2008.
221. R. A. Kowluru, Q. Zhong, J. M. Santos, M. Thandampallayam, D. Putt, and D. L. Gierhart, "Beneficial effects of the nutritional supplements on the development of diabetic retinopathy, " Nutrition and Metabolism, vol. 11, no. 1, article 8, 2014.
222. Age-Related Eye Disease Study 2 Research Group, "Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial, " Journal of the American Medical Association, vol. 309, no. 19, pp. 2005-2015, 2013.
223. R. Simó and C. Hernández, "Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives, " Trends in Endocrinology and Metabolism, vol. 25, no. 1, pp. 23-33, 2014.
224. C. E. Riva, E. Logean, and B. Falsini, "Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina, " Progress in Retinal and Eye Research, vol. 24, no. 2, pp. 183-215, 2005.
225. F. Formaz, C. E. Riva, and M. Geiser, "Diffuse luminance flicker increases retinal vessel diameter in humans, " Current Eye Research, vol. 16, no. 12, pp. 1252-1257, 1997.
226. A. Lecleire-Collet, I. Audo, M. Aout et al., "Evaluation of retinal function and flicker light-induced retinal vascular response in normotensive patients with diabetes without retinopathy, " Investigative Ophthalmology and Visual Science, vol. 52, no. 6, pp. 2861-2867, 2011.
227. T. T. Nguyen, R. Kawasaki, J. J. Wang et al., "Flicker lightinduced retinal vasodilation in diabetes and diabetic retinopathy, " Diabetes Care, vol. 32, no. 11, pp. 2075-2080, 2009.
228. M. Tyrberg, U. Lindblad, A. Melander, M. Lövestam-Adrian, V. Ponjavic, and S. Andréasson, "Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy, " Documenta Ophthalmologica, vol. 123, no. 3, pp. 193-198, 2011.
229. A. Mishra and E. A. Newman, "Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy, " Glia, vol. 58, no. 16, pp. 1996-2004, 2010.
230. S. S. F. Cheung, J. W. C. Leung, A. K. M. Lam et al., "Selective over-expression of endothelin-1 in endothelial cells exacerbates inner retinal edema and neuronal death in ischemic retina, " PLoS ONE, vol. 6, no. 10, Article IDe26184, 2011.
231. M. Tonari, T. Kurimoto, T. Horie, T. Sugiyama, T. Ikeda, and H. Oku, "Blocking endothelin-B receptors rescues retinal ganglion cells from optic nerve injury through suppression of neuroinflammation, " Investigative Ophthalmology and Visual Science, vol. 53, no. 7, pp. 3490-3500, 2012.
232. A. Z. Minton, N. R. Phatak, D. L. Stankowska et al., "Endothelin B receptors contribute to retinal ganglion cell loss in a ratmodel of glaucoma, " PLoS ONE, vol. 7, no. 8, Article ID e43199, 2012.
233. X.-S. Mi, X. Zhang, Q. Feng, A. C. Y. Lo, S. K. Chung, and K.-F. So, "Progressive retinal degeneration in transgenic mice with overexpression of endothelin-1 in vascular endothelial cells, " Investigative Ophthalmology and Visual Science, vol. 53, no. 8, pp. 4842-4851, 2012.
234. J. C. Chou, S. D. Rollins, M. Ye, D. Batlle, and A. A. Fawzi, "Endothelin receptor-a antagonist attenuates retinal vascular and neuroretinal pathology in diabetic mice, " Investigative Ophthalmology and Visual Science, vol. 55, no. 4, pp. 2516-2525, 2014.
235. J. Kusari, S. Zhou, E. Padillo, K. G. Clarke, and D. W. Gil, "Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats, " Investigative Ophthalmology and Visual Science, vol. 48, no. 11, pp. 5152-5159, 2007.
236. D. F. Sena and K. Lindsley, "Neuroprotection for treatment of glaucoma in adults, " Cochrane Database Of Systematic Reviews, vol. 2, Article ID CD006539, 2013.
237. S. A. Jayakody, A. Gonzalez-Cordero, R. R. Ali, and R. A. Pearson, "Cellular strategies for retinal repair by photoreceptor replacement, " Progress in Retinal and Eye Research, vol. 46, pp. 31-66, 2015.
238. D. Ruminski, B. L. Sikorski, D. Bukowska et al., "OCT angiography by absolute intensity difference applied to normal and diseased human retinas, " Biomedical Optics Express, vol. 6, no. 8, pp. 2738-2754, 2015.
239. T. Bek, "Fine structure in diabetic retinopathy lesions as observed by adaptive optics imaging. A qualitative study, " Acta Ophthalmologica, vol. 92, no. 8, pp. 753-758, 2014.
240. S. Arichika, A. Uji, T. Murakami et al., "Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy, " Investigative Ophthalmology and Visual Science, vol. 55, no. 12, pp. 8513-8522, 2014.
241. R. Gaudana, J. Jwala, S. H. S. Boddu, and A. K. Mitra, "Recent perspectives in ocular drug delivery, " Pharmaceutical Research, vol. 26, no. 5, pp. 1197-1216, 2009.