1932

Abstract

Although diabetic retinopathy (DR) is clinically diagnosed as a vascular disease, many studies find retinal neuronal and visual dysfunction before the onset of vascular DR. This suggests that DR should be viewed as a neurovascular disease. Prior to the onset of DR, human patients have compromised electroretinograms that indicate a disruption of normal function, particularly in the inner retina. They also exhibit reduced contrast sensitivity. These early changes, especially those due to dysfunction in the inner retina, are also seen in rodent models of diabetes in the early stages of the disease. Rodent models of diabetes exhibit several neuronal mechanisms, such as reduced evoked GABA release, increased excitatory glutamate signaling, and reduced dopamine signaling, that suggest specific neuronal deficits. This suggests that understanding neuronal deficits may lead to early diabetes treatments to ameliorate neuronal dysfunction.

Keyword(s): diabeteshumanmouseneuronsphysiologyratretinarodent
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2023-09-15
2024-05-05
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Literature Cited

  1. Abcouwer SF, Gardner TW. 2014. Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. Ann. N. Y. Acad. Sci. 1311:174–90
    [Google Scholar]
  2. Ali SA, Zaitone SA, Dessouki AA, Ali AA. 2019. Pregabalin affords retinal neuroprotection in diabetic rats: suppression of retinal glutamate, microglia cell expression and apoptotic cell death. Exp. Eye Res. 184:78–90
    [Google Scholar]
  3. Aung MH, Kim MK, Olson DE, Thule PM, Pardue MT. 2013. Early visual deficits in streptozotocin-induced diabetic Long Evans rats. Investig. Ophthalmol. Vis. Sci. 54:1370–77
    [Google Scholar]
  4. Aung MH, Park HN, Han MK, Obertone TS, Abey J et al. 2014. Dopamine deficiency contributes to early visual dysfunction in a rodent model of type 1 diabetes. J. Neurosci. 34:726–36
    [Google Scholar]
  5. Baptista FI, Gaspar JM, Cristovao A, Santos PF, Kofalvi A, Ambrosio AF. 2011. Diabetes induces early transient changes in the content of vesicular transporters and no major effects in neurotransmitter release in hippocampus and retina. Brain Res. 1383:257–69
    [Google Scholar]
  6. Barber AJ, Antonetti DA, Kern TS, Reiter CE, Soans RS et al. 2005. The Ins2Akita mouse as a model of early retinal complications in diabetes. Investig. Ophthalmol. Vis. Sci. 46:2210–18
    [Google Scholar]
  7. Barber AJ, Baccouche B. 2017. Neurodegeneration in diabetic retinopathy: potential for novel therapies. Vis. Res. 139:82–92
    [Google Scholar]
  8. Berkowitz BA, Kern TS, Bissig D, Patel P, Bhatia A et al. 2015. Systemic retinaldehyde treatment corrects retinal oxidative stress, rod dysfunction, and impaired visual performance in diabetic mice. Investig. Ophthalmol. Vis. Sci. 56:6294–303
    [Google Scholar]
  9. Bresnick GH, Palta M. 1987. Predicting progression to severe proliferative diabetic retinopathy. Arch. Ophthalmol. 105:810–14
    [Google Scholar]
  10. Bronson-Castain KW, Bearse MA Jr., Neuville J, Jonasdottir S, King-Hooper B et al. 2012. Early neural and vascular changes in the adolescent type 1 and type 2 diabetic retina. Retina 32:92–102
    [Google Scholar]
  11. Brown DM, Heier JS, Clark WL, Boyer DS, Vitti R et al. 2013. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am. J. Ophthalmol. 155:429–37.e7
    [Google Scholar]
  12. Bui BV, Loeliger M, Thomas M, Vingrys AJ, Rees SM et al. 2009. Investigating structural and biochemical correlates of ganglion cell dysfunction in streptozotocin-induced diabetic rats. Exp. Eye Res. 88:1076–83
    [Google Scholar]
  13. Calvo E, Milla-Navarro S, Ortuno-Lizaran I, Gomez-Vicente V, Cuenca N et al. 2020. Deleterious effect of NMDA plus kainate on the inner retinal cells and ganglion cell projection of the mouse. Int. J. Mol. Sci. 21:1570
    [Google Scholar]
  14. Castilho A, Ambrosio AF, Hartveit E, Veruki ML. 2015. Disruption of a neural microcircuit in the rod pathway of the mammalian retina by diabetes mellitus. J. Neurosci. 35:5422–33
    [Google Scholar]
  15. Chakravarthy H, Devanathan V. 2018. Molecular mechanisms mediating diabetic retinal neurodegeneration: potential research avenues and therapeutic targets. J. Mol. Neurosci. 66:445–61
    [Google Scholar]
  16. Cohen AI, Todd RD, Harmon S, O'Malley KL. 1992. Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase. PNAS 89:12093–97
    [Google Scholar]
  17. Cui RZ, Wang L, Qiao SN, Wang YC, Wang X et al. 2019. ON-type retinal ganglion cells are preferentially affected in STZ-induced diabetic mice. Investig. Ophthalmol. Vis. Sci. 60:1644–56
    [Google Scholar]
  18. Derouiche A, Asan E. 1999. The dopamine D2 receptor subfamily in rat retina: ultrastructural immunogold and in situ hybridization studies. Eur. J. Neurosci. 11:1391–402
    [Google Scholar]
  19. Dhamdhere KP, Bearse MA Jr., Harrison W, Barez S, Schneck ME, Adams AJ. 2012. Associations between local retinal thickness and function in early diabetes. Investig. Ophthalmol. Vis. Sci. 53:6122–28
    [Google Scholar]
  20. Di Leo MA, Caputo S, Falsini B, Porciatti V, Minnella A et al. 1992. Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes. Diabetes Care 15:620–25
    [Google Scholar]
  21. Dosso AA, Bonvin ER, Morel Y, Golay A, Assal JP, Leuenberger PM. 1996. Risk factors associated with contrast sensitivity loss in diabetic patients. Graefes Arch. Clin. Exp. Ophthalmol. 234:300–5
    [Google Scholar]
  22. Early Treat. Diabet. Retin. Study Res. Group 1991. Fundus photographic risk factors for progression of diabetic retinopathy: ETDRS report number 12. Ophthalmology 98:823–33
    [Google Scholar]
  23. El-Remessy AB, Al-Shabrawey M, Khalifa Y, Tsai NT, Caldwell RB, Liou GI 2006. Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. Am. J. Pathol. 168:235–44
    [Google Scholar]
  24. Farshi P, Fyk-Kolodziej B, Krolewski DM, Walker PD, Ichinose T. 2016. Dopamine D1 receptor expression is bipolar cell type-specific in the mouse retina. J. Comp. Neurol. 524:2059–79
    [Google Scholar]
  25. Flood MD, Wellington AJ, Cruz LA, Eggers ED. 2020. Early diabetes impairs ON sustained ganglion cell light responses and adaptation without cell death or dopamine insensitivity. Exp. Eye Res. 200:108223
    [Google Scholar]
  26. Flood MD, Wellington AJ, Eggers ED. 2022. Impaired light adaptation of ON-sustained ganglion cells in early diabetes is attributable to diminished response to dopamine D4 receptor activation. Investig. Ophthalmol. Vis. Sci. 63:33
    [Google Scholar]
  27. Furman BL. 2015. Streptozotocin-induced diabetic models in mice and rats. Curr. Protoc. Pharmacol. 70:5.47
    [Google Scholar]
  28. Garhofer G, Chua J, Tan B, Wong D, Schmidl D, Schmetterer L. 2020. Retinal neurovascular coupling in diabetes. J. Clin. Med. 9:2829
    [Google Scholar]
  29. Gastinger MJ, Kunselman AR, Conboy EE, Bronson SK, Barber AJ. 2008. Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice. Investig. Ophthalmol. Vis. Sci. 49:2635–42
    [Google Scholar]
  30. Gastinger MJ, Singh RS, Barber AJ. 2006. Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. Investig. Ophthalmol. Vis. Sci. 47:3143–50
    [Google Scholar]
  31. Gonzalez VH, Campbell J, Holekamp NM, Kiss S, Loewenstein A et al. 2016. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data. Am. J. Ophthalmol. 172:72–79
    [Google Scholar]
  32. Green DG, Kapousta-Bruneau NV. 1999. A dissection of the electroretinogram from the isolated rat retina with microelectrodes and drugs. Vis. Neurosci. 16:727–41
    [Google Scholar]
  33. Gundogan FC, Akay F, Uzun S, Yolcu U, Cagiltay E, Toyran S. 2016. Early neurodegeneration of the inner retinal layers in type 1 diabetes mellitus. Ophthalmologica 235:125–32
    [Google Scholar]
  34. Harris A, Arend O, Danis RP, Evans D, Wolf S, Martin BJ. 1996. Hyperoxia improves contrast sensitivity in early diabetic retinopathy. Br. J. Ophthalmol. 80:209–13
    [Google Scholar]
  35. Harrison WW, Bearse MA Jr., Ng JS, Jewell NP, Barez S et al. 2011. Multifocal electroretinograms predict onset of diabetic retinopathy in adult patients with diabetes. Investig. Ophthalmol. Vis. Sci. 52:772–77
    [Google Scholar]
  36. Hernandez C, Garcia-Ramirez M, Corraliza L, Fernandez-Carneado J, Farrera-Sinfreu J et al. 2013. Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes. Diabetes 62:2569–78
    [Google Scholar]
  37. Herrmann R, Heflin SJ, Hammond T, Lee B, Wang J et al. 2011. Rod vision is controlled by dopamine-dependent sensitization of rod bipolar cells by GABA. Neuron 72:101–10
    [Google Scholar]
  38. Hombrebueno JR, Chen M, Penalva RG, Xu H. 2014. Loss of synaptic connectivity, particularly in second order neurons is a key feature of diabetic retinal neuropathy in the Ins2Akita mouse. PLOS ONE 9:e97970
    [Google Scholar]
  39. Honda M, Inoue M, Okada Y, Yamamoto M. 1998. Alteration of the GABAergic neuronal system of the retina and superior colliculus in streptozotocin-induced diabetic rat. Kobe J. Med. Sci. 44:1–8
    [Google Scholar]
  40. Hood DC, Frishman LJ, Saszik S, Viswanathan S. 2002. Retinal origins of the primate multifocal ERG: implications for the human response. Investig. Ophthalmol. Vis. Sci. 43:1673–85
    [Google Scholar]
  41. Howell SJ, Mekhail MN, Azem R, Ward NL, Kern TS. 2013. Degeneration of retinal ganglion cells in diabetic dogs and mice: relationship to glycemic control and retinal capillary degeneration. Mol. Vis. 19:1413–21
    [Google Scholar]
  42. Ishikawa A, Ishiguro S, Tamai M. 1996. Changes in GABA metabolism in streptozotocin-induced diabetic rat retinas. Curr. Eye Res. 15:63–71
    [Google Scholar]
  43. Jackson GR, Barber AJ. 2010. Visual dysfunction associated with diabetic retinopathy. Curr. Diabetes Rep. 10:380–84
    [Google Scholar]
  44. Juen S, Kieselbach GF. 1990. Electrophysiological changes in juvenile diabetics without retinopathy. Arch. Ophthalmol. 108:372–75
    [Google Scholar]
  45. Kaneko M, Sugawara T, Tazawa Y. 2000. Electrical responses from the inner retina of rats with streptozotocin-induced early diabetes mellitus. Nippon Ganka Gakkai Zasshi 104:775–78
    [Google Scholar]
  46. Karti O, Nalbantoglu O, Abali S, Ayhan Z, Tunc S et al. 2017. Retinal ganglion cell loss in children with type 1 diabetes mellitus without diabetic retinopathy. Ophthalmic Surg. Lasers Imaging Retina 48:473–77
    [Google Scholar]
  47. Kawasaki K, Yonemura K, Yokogawa Y, Saito N, Kawakita S. 1986. Correlation between ERG oscillatory potential and psychophysical contrast sensitivity in diabetes. Doc. Ophthalmol. 64:209–15
    [Google Scholar]
  48. Kern TS, Du Y, Tang J, Lee CA, Liu H et al. 2021. Regulation of adrenergic, serotonin, and dopamine receptors to inhibit diabetic retinopathy: monotherapies versus combination therapies. Mol. Pharmacol. 100:470–79
    [Google Scholar]
  49. Kim MK, Aung MH, Mees L, Olson DE, Pozdeyev N et al. 2018. Dopamine deficiency mediates early rod-driven inner retinal dysfunction in diabetic mice. Investig. Ophthalmol. Vis. Sci. 59:572–81
    [Google Scholar]
  50. Kirwin SJ, Kanaly ST, Hansen CR, Cairns BJ, Ren M, Edelman JL. 2011. Retinal gene expression and visually evoked behavior in diabetic Long Evans rats. Investig. Ophthalmol. Vis. Sci. 52:7654–63
    [Google Scholar]
  51. Kizawa J, Machida S, Kobayashi T, Gotoh Y, Kurosaka D. 2006. Changes of oscillatory potentials and photopic negative response in patients with early diabetic retinopathy. Jpn. J. Ophthalmol. 50:367–73
    [Google Scholar]
  52. Kohzaki K, Vingrys AJ, Bui BV. 2008. Early inner retinal dysfunction in streptozotocin-induced diabetic rats. Investig. Ophthalmol. Vis. Sci. 49:3595–604
    [Google Scholar]
  53. Kolb H. 1987. Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice. Diabetes Metab. Rev. 3:751–78
    [Google Scholar]
  54. Kowluru RA, Engerman RL, Case GL, Kern TS. 2001. Retinal glutamate in diabetes and effect of antioxidants. Neurochem. Int. 38:385–90
    [Google Scholar]
  55. Kur J, Burian MA, Newman EA. 2016. Light adaptation does not prevent early retinal abnormalities in diabetic rats. Sci. Rep. 6:21075
    [Google Scholar]
  56. Lahouaoui H, Coutanson C, Cooper HM, Bennis M, Dkhissi-Benyahya O. 2016. Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina. Mol. Vis. 22:959–69
    [Google Scholar]
  57. Laron M, Bearse MA Jr., Bronson-Castain K, Jonasdottir S, King-Hooper B et al. 2012. Association between local neuroretinal function and control of adolescent type 1 diabetes. Investig. Ophthalmol. Vis. Sci. 53:7071–76
    [Google Scholar]
  58. Lau JC, Kroes RA, Moskal JR, Linsenmeier RA. 2013. Diabetes changes expression of genes related to glutamate neurotransmission and transport in the Long-Evans rat retina. Mol. Vis. 19:1538–53
    [Google Scholar]
  59. Layton CJ, Safa R, Osborne NN. 2007. Oscillatory potentials and the b-wave: partial masking and interdependence in dark adaptation and diabetes in the rat. Graefes Arch. Clin. Exp. Ophthalmol. 245:1335–45
    [Google Scholar]
  60. Lelyte I, Ahmed Z, Kaja S, Kalesnykas G. 2022. Structure-function relationships in the rodent streptozotocin-induced model for diabetic retinopathy: a systematic review. J. Ocul. Pharmacol. Ther. 38:271–86
    [Google Scholar]
  61. Li H, Zhang Z, Blackburn MR, Wang SW, Ribelayga CP, O'Brien J. 2013. Adenosine and dopamine receptors coregulate photoreceptor coupling via gap junction phosphorylation in mouse retina. J. Neurosci. 33:3135–50
    [Google Scholar]
  62. Li J, Chen P, Bao Y, Sun Y, He J, Liu X. 2020. PET imaging of vesicular monoamine transporter 2 in early diabetic retinopathy using [(18)F]FP-(+)-DTBZ. Mol. Imaging Biol. 22:1161–69
    [Google Scholar]
  63. Li X, Zhang M, Tang W. 2013. Effects of melatonin on streptozotocin-induced retina neuronal apoptosis in high blood glucose rat. Neurochem. Res. 38:669–76
    [Google Scholar]
  64. Lieth E, Barber AJ, Xu B, Dice C, Ratz MJ et al. 1998. Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. Diabetes 47:815–20
    [Google Scholar]
  65. Liu F, Saul AB, Pichavaram P, Xu Z, Rudraraju M et al. 2020. Pharmacological inhibition of spermine oxidase reduces neurodegeneration and improves retinal function in diabetic mice. J. Clin. Med. 9:340
    [Google Scholar]
  66. Lopes de Faria JM, Katsumi O, Cagliero E, Nathan D, Hirose T. 2001. Neurovisual abnormalities preceding the retinopathy in patients with long-term type 1 diabetes mellitus. Graefes Arch. Clin. Exp. Ophthalmol. 239:643–48
    [Google Scholar]
  67. Lopes de Faria JM, Russ H, Costa VP. 2002. Retinal nerve fibre layer loss in patients with type 1 diabetes mellitus without retinopathy. Br. J. Ophthalmol. 86:725–28
    [Google Scholar]
  68. Ly A, Scheerer MF, Zukunft S, Muschet C, Merl J et al. 2014. Retinal proteome alterations in a mouse model of type 2 diabetes. Diabetologia 57:192–203
    [Google Scholar]
  69. Lynch SK, Abramoff MD. 2017. Diabetic retinopathy is a neurodegenerative disorder. Vis. Res. 139:101–7
    [Google Scholar]
  70. Masland RH. 2012. The neuronal organization of the retina. Neuron 76:266–80
    [Google Scholar]
  71. McAnany JJ, Liu K, Park JC. 2020. Electrophysiological measures of dysfunction in early-stage diabetic retinopathy: no correlation between cone phototransduction and oscillatory potential abnormalities. Doc. Ophthalmol. 140:31–42
    [Google Scholar]
  72. McAnany JJ, Park JC. 2019. Cone photoreceptor dysfunction in early-stage diabetic retinopathy: association between the activation phase of cone phototransduction and the flicker electroretinogram. Investig. Ophthalmol. Vis. Sci. 60:64–72
    [Google Scholar]
  73. McCall MA, Lukasiewicz PD, Gregg RG, Peachey NS. 2002. Elimination of the rho1 subunit abolishes GABA(C) receptor expression and alters visual processing in the mouse retina. J. Neurosci. 22:4163–74
    [Google Scholar]
  74. McFarlane M, Wright T, Stephens D, Nilsson J, Westall CA. 2012. Blue flash ERG PhNR changes associated with poor long-term glycemic control in adolescents with type 1 diabetes. Investig. Ophthalmol. Vis. Sci. 53:741–48
    [Google Scholar]
  75. Miller WP, Yang C, Mihailescu ML, Moore JA, Dai W et al. 2018. Deletion of the Akt/mTORC1 repressor REDD1 prevents visual dysfunction in a rodent model of type 1 diabetes. Diabetes 67:110–19
    [Google Scholar]
  76. Mills SL, Xia XB, Hoshi H, Firth SI, Rice ME et al. 2007. Dopaminergic modulation of tracer coupling in a ganglion-amacrine cell network. Vis. Neurosci. 24:593–608
    [Google Scholar]
  77. Mishra A, Newman EA. 2010. Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy. Glia 58:1996–2004
    [Google Scholar]
  78. Mishra A, Newman EA. 2011. Aminoguanidine reverses the loss of functional hyperemia in a rat model of diabetic retinopathy. Front. Neuroenerg. 3:10
    [Google Scholar]
  79. Moller A, Eysteinsson T. 2003. Modulation of the components of the rat dark-adapted electroretinogram by the three subtypes of GABA receptors. Vis. Neurosci. 20:535–42
    [Google Scholar]
  80. Montesano G, Ometto G, Higgins BE, Das R, Graham KW et al. 2021. Evidence for structural and functional damage of the inner retina in diabetes with no diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 62:35
    [Google Scholar]
  81. Moore-Dotson JM, Beckman JJ, Mazade RE, Hoon M, Bernstein AS et al. 2016. Early retinal neuronal dysfunction in diabetic mice: Reduced light-evoked inhibition increases rod pathway signaling. Investig. Ophthalmol. Vis. Sci. 57:1418–30
    [Google Scholar]
  82. Moore-Dotson JM, Eggers ED. 2019. Reductions in calcium signaling limit inhibition to diabetic retinal rod bipolar cells. Investig. Ophthalmol. Vis. Sci. 60:4063–73
    [Google Scholar]
  83. Motz CT, Chesler KC, Allen RS, Bales KL, Mees LM et al. 2020. Novel detection and restorative levodopa treatment for preclinical diabetic retinopathy. Diabetes 69:1518–27
    [Google Scholar]
  84. Naarendorp F, Sieving PA. 1991. The scotopic threshold response of the cat ERG is suppressed selectively by GABA and glycine. Vis. Res. 31:1–15
    [Google Scholar]
  85. Naderi A, Zahed R, Aghajanpour L, Amoli FA, Lashay A 2019. Long term features of diabetic retinopathy in streptozotocin-induced diabetic Wistar rats. Exp. Eye Res. 184:213–20
    [Google Scholar]
  86. NCD Risk Factor Collab 2016. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 387:1513–30
    [Google Scholar]
  87. Ng JS, Bearse MA Jr., Schneck ME, Barez S, Adams AJ. 2008. Local diabetic retinopathy prediction by multifocal ERG delays over 3 years. Investig. Ophthalmol. Vis. Sci. 49:1622–28
    [Google Scholar]
  88. Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S et al. 2012. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119:789–801
    [Google Scholar]
  89. Nishimura C, Kuriyama K. 1985. Alterations in the retinal dopaminergic neuronal system in rats with streptozotocin-induced diabetes. J. Neurochem. 45:448–55
    [Google Scholar]
  90. Olivares AM, Althoff K, Chen GF, Wu S, Morrisson MA et al. 2017. Animal models of diabetic retinopathy. Curr. Diabetes Rep. 17:93
    [Google Scholar]
  91. Osaadon P, Fagan XJ, Lifshitz T, Levy J. 2014. A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye 28:510–20
    [Google Scholar]
  92. Ou K, Li Y, Liu L, Li H, Cox K et al. 2022. Recent developments of neuroprotective agents for degenerative retinal disorders. Neural Regen. Res. 17:1919–28
    [Google Scholar]
  93. Pardue MT, Allen RS. 2018. Neuroprotective strategies for retinal disease. Prog. Retin. Eye Res. 65:50–76
    [Google Scholar]
  94. Pardue MT, Barnes CS, Kim MK, Aung MH, Amarnath R et al. 2014. Rodent hyperglycemia-induced inner retinal deficits are mirrored in human diabetes. Transl. Vis. Sci. Technol. 3:6
    [Google Scholar]
  95. Parisi V, Uccioli L, Monticone G, Parisi L, Manni G et al. 1997. Electrophysiological assessment of visual function in IDDM patients. Electroencephalogr. Clin. Neurophysiol. 104:171–79
    [Google Scholar]
  96. Pemp B, Garhofer G, Weigert G, Karl K, Resch H et al. 2009. Reduced retinal vessel response to flicker stimulation but not to exogenous nitric oxide in type 1 diabetes. Investig. Ophthalmol. Vis. Sci. 50:4029–32
    [Google Scholar]
  97. Piano I, Novelli E, Della Santina L, Strettoi E, Cervetto L, Gargini C 2016. Involvement of autophagic pathway in the progression of retinal degeneration in a mouse model of diabetes. Front. Cell Neurosci. 10:42
    [Google Scholar]
  98. Pinilla I, Idoipe M, Perdices L, Sanchez-Cano A, Acha J et al. 2020. Changes in total and inner retinal thicknesses in type 1 diabetes with no retinopathy after 8 years of follow-up. Retina 40:1379–86
    [Google Scholar]
  99. Pramanik S, Chowdhury S, Ganguly U, Banerjee A, Bhattacharya B, Mondal LK. 2020. Visual contrast sensitivity could be an early marker of diabetic retinopathy. Heliyon 6:e05336
    [Google Scholar]
  100. Prusky GT, Alam NM, Beekman S, Douglas RM. 2004. Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. Investig. Ophthalmol. Vis. Sci. 45:4611–16
    [Google Scholar]
  101. Ramsey DJ, Ripps H, Qian H. 2006. An electrophysiological study of retinal function in the diabetic female rat. Investig. Ophthalmol. Vis. Sci. 47:5116–24
    [Google Scholar]
  102. Robson JG, Frishman LJ. 1998. Dissecting the dark-adapted electroretinogram. Doc. Ophthalmol. 95:187–215
    [Google Scholar]
  103. Robson JG, Maeda H, Saszik SM, Frishman LJ. 2004. In vivo studies of signaling in rod pathways of the mouse using the electroretinogram. Vis. Res. 44:3253–68
    [Google Scholar]
  104. Sahin M, Sahin A, Kilinc F, Karaalp U, Yuksel H et al. 2018. Early detection of macular and peripapillary changes with spectralis optical coherence tomography in patients with prediabetes. Arch. Physiol. Biochem. 124:75–79
    [Google Scholar]
  105. Samuels IS, Bell BA, Pereira A, Saxon J, Peachey NS. 2015. Early retinal pigment epithelium dysfunction is concomitant with hyperglycemia in mouse models of type 1 and type 2 diabetes. J. Neurophysiol. 113:1085–99
    [Google Scholar]
  106. Samuels IS, Lee CA, Petrash JM, Peachey NS, Kern TS. 2012. Exclusion of aldose reductase as a mediator of ERG deficits in a mouse model of diabetic eye disease. Vis. Neurosci. 29:267–74
    [Google Scholar]
  107. Santiago AR, Gaspar JM, Baptista FI, Cristovao AJ, Santos PF et al. 2009. Diabetes changes the levels of ionotropic glutamate receptors in the rat retina. Mol. Vis. 15:1620–30
    [Google Scholar]
  108. Schluter A, Aksan B, Diem R, Fairless R, Mauceri D. 2020. VEGFD protects retinal ganglion cells and, consequently, capillaries against excitotoxic injury. Mol. Ther. Methods Clin. Dev. 17:281–99
    [Google Scholar]
  109. Schmidt-Erfurth U, Chong V, Loewenstein A, Larsen M, Souied E et al. 2014. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br. J. Ophthalmol. 98:1144–67
    [Google Scholar]
  110. Scuderi S, D'Amico AG, Castorina A, Federico C, Marrazzo G et al. 2014. Davunetide (NAP) protects the retina against early diabetic injury by reducing apoptotic death. J. Mol. Neurosci. 54:395–404
    [Google Scholar]
  111. Semkova I, Huemmeke M, Ho MS, Merkl B, Abari E et al. 2010. Retinal localization of the glutamate receptor GluR2 and GluR2-regulating proteins in diabetic rats. Exp. Eye Res. 90:244–53
    [Google Scholar]
  112. Sergeys J, Etienne I, Van Hove I, Lefevere E, Stalmans I et al. 2019. Longitudinal in vivo characterization of the streptozotocin-induced diabetic mouse model: focus on early inner retinal responses. Investig. Ophthalmol. Vis. Sci. 60:807–22
    [Google Scholar]
  113. Shinoda K, Rejdak R, Schuettauf F, Blatsios G, Volker M et al. 2007. Early electroretinographic features of streptozotocin-induced diabetic retinopathy. Clin. Exp. Ophthalmol. 35:847–54
    [Google Scholar]
  114. Simonsen SE. 1980. The value of the oscillatory potential in selecting juvenile diabetics at risk of developing proliferative retinopathy. Acta Ophthalmol. 58:865–78
    [Google Scholar]
  115. Smith BJ, Cote PD, Tremblay F. 2015. Dopamine modulation of rod pathway signaling by suppression of GABAC feedback to rod-driven depolarizing bipolar cells. Eur. J. Neurosci. 42:2258–70
    [Google Scholar]
  116. Sohn EH, van Dijk HW, Jiao C, Kok PH, Jeong W et al. 2016. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. PNAS 113:E2655–64
    [Google Scholar]
  117. Sundstrom JM, Hernandez C, Weber SR, Zhao Y, Dunklebarger M et al. 2018. Proteomic analysis of early diabetic retinopathy reveals mediators of neurodegenerative brain diseases. Investig. Ophthalmol. Vis. Sci. 59:2264–74
    [Google Scholar]
  118. Tan W, Wright T, Dupuis A, Lakhani E, Westall C. 2014. Localizing functional damage in the neural retina of adolescents and young adults with type 1 diabetes. Investig. Ophthalmol. Vis. Sci. 55:2432–41
    [Google Scholar]
  119. Travis AM, Heflin SJ, Hirano AA, Brecha NC, Arshavsky VY. 2018. Dopamine-dependent sensitization of rod bipolar cells by GABA is conveyed through wide-field amacrine cells. J. Neurosci. 38:723–32
    [Google Scholar]
  120. Uccioli L, Parisi V, Monticone G, Parisi L, Durola L et al. 1995. Electrophysiological assessment of visual function in newly-diagnosed IDDM patients. Diabetologia 38:804–8
    [Google Scholar]
  121. Vadala M, Anastasi M, Lodato G, Cillino S. 2002. Electroretinographic oscillatory potentials in insulin-dependent diabetes patients: a long-term follow-up. Acta Ophthalmol. Scand. 80:305–9
    [Google Scholar]
  122. VanGuilder HD, Brucklacher RM, Patel K, Ellis RW, Freeman WM, Barber AJ. 2008. Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina. Eur. J. Neurosci. 28:1–11
    [Google Scholar]
  123. Verma A, Raman R, Vaitheeswaran K, Pal SS, Laxmi G et al. 2012. Does neuronal damage precede vascular damage in subjects with type 2 diabetes mellitus and having no clinical diabetic retinopathy?. Ophthalmic Res. 47:202–7
    [Google Scholar]
  124. Veruki ML. 1997. Dopaminergic neurons in the rat retina express dopamine D2/3 receptors. Eur. J. Neurosci. 9:1096–100
    [Google Scholar]
  125. Veruki ML, Wassle H. 1996. Immunohistochemical localization of dopamine D1 receptors in rat retina. Eur. J. Neurosci. 8:2286–97
    [Google Scholar]
  126. Viswanathan S, Frishman LJ, Robson JG, Harwerth RS, Smith EL III. 1999. The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma. Investig. Ophthalmol. Vis. Sci. 40:1124–36
    [Google Scholar]
  127. Wachtmeister L. 1980. Further studies of the chemical sensitivity of the oscillatory potentials of the electroretinogram (ERG) I. GABA- and glycine antagonists. Acta Ophthalmol. 58:712–25
    [Google Scholar]
  128. Wachtmeister L, Dowling JE. 1978. The oscillatory potentials of the mudpuppy retina. Investig. Ophthalmol. Vis. Sci. 17:1176–88
    [Google Scholar]
  129. Wilkinson CP, Ferris FL III, Klein RE, Lee PP, Agardh CD et al. 2003. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110:1677–82
    [Google Scholar]
  130. Witkovsky P. 2004. Dopamine and retinal function. Doc. Ophthalmol. 108:17–40
    [Google Scholar]
  131. Yang S, Zhao J, Sun X. 2016. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des. Dev. Ther. 10:1857–67
    [Google Scholar]
  132. Yang Y, Mao D, Chen X, Zhao L, Tian Q et al. 2012. Decrease in retinal neuronal cells in streptozotocin-induced diabetic mice. Mol. Vis. 18:1411–20
    [Google Scholar]
  133. Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW et al. 2012. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35:556–64
    [Google Scholar]
  134. Yoshida A, Kojima M, Ogasawara H, Ishiko S. 1991. Oscillatory potentials and permeability of the blood-retinal barrier in noninsulin-dependent diabetic patients without retinopathy. Ophthalmology 98:1266–71
    [Google Scholar]
  135. Yu J, Wang L, Weng SJ, Yang XL, Zhang DQ, Zhong YM. 2013. Hyperactivity of ON-type retinal ganglion cells in streptozotocin-induced diabetic mice. PLOS ONE 8:e76049
    [Google Scholar]
  136. Zhang Y, Zhang J, Wang Q, Lei X, Chu Q et al. 2011. Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats. Investig. Ophthalmol. Vis. Sci. 52:278–85
    [Google Scholar]
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