Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-23T02:42:54.032Z Has data issue: false hasContentIssue false
  • English
  • Français

The effects of early diabetes on inner retinal neurons

Published online by Cambridge University Press:  16 September 2020

Erika D. Eggers Open the ORCID record for Erika D. Eggers [Opens in a new window]  and
Teresia A. Carreon
Erika D. Eggers*
Affiliation:
Departments of Physiology Biomedical Engineering, University of Arizona, Tucson, Arizona Department of Biomedical Engineering, University of Arizona, Tucson, Arizona
Teresia A. Carreon
Affiliation:
Departments of Physiology Biomedical Engineering, University of Arizona, Tucson, Arizona Department of Biomedical Engineering, University of Arizona, Tucson, Arizona
*
*Address correspondence to: Erika Eggers, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Diabetic retinopathy is now well understood as a neurovascular disease. Significant deficits early in diabetes are found in the inner retina that consists of bipolar cells that receive inputs from rod and cone photoreceptors, ganglion cells that receive inputs from bipolar cells, and amacrine cells that modulate these connections. These functional deficits can be measured in vivo in diabetic humans and animal models using the electroretinogram (ERG) and behavioral visual testing. Early effects of diabetes on both the human and animal model ERGs are changes to the oscillatory potentials that suggest dysfunctional communication between amacrine cells and bipolar cells as well as ERG measures that suggest ganglion cell dysfunction. These are coupled with changes in contrast sensitivity that suggest inner retinal changes. Mechanistic in vitro neuronal studies have suggested that these inner retinal changes are due to decreased inhibition in the retina, potentially due to decreased gamma aminobutyric acid (GABA) release, increased glutamate release, and increased excitation of retinal ganglion cells. Inner retinal deficits in dopamine levels have also been observed that can be reversed to limit inner retinal damage. Inner retinal targets present a promising new avenue for therapies for early-stage diabetic eye disease.

Keywords

Diabetesinhibitionretinaamacrine cellamacrine cell
Type
Review Article
Information
Visual Neuroscience , Volume 37 , 2020 , E006
Check for updates
Copyright
© The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abcouwer, S.F. & Gardner, T.W. (2014). Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. Annals of the New York Academy of Sciences 1311, 174–190.CrossRefGoogle ScholarPubMed
Ali, S.A., Zaitone, S.A., Dessouki, A.A. & Ali, A.A. (2019). Pregabalin affords retinal neuroprotection in diabetic rats: Suppression of retinal glutamate, microglia cell expression and apoptotic cell death. Experimental Eye Research 184, 78–90.CrossRefGoogle ScholarPubMed
Archibald, N.K., Clarke, M.P., Mosimann, U.P. & Burn, D.J. (2009). The retina in Parkinson’s disease. Brain 132, 1128–1145.CrossRefGoogle ScholarPubMed
Aung, M.H., Kim, M.K., Olson, D.E., Thule, P.M. & Pardue, M.T. (2013). Early visual deficits in streptozotocin-induced diabetic long evans rats. Investigative Ophthalmology and Visual Science 54, 1370–1377.CrossRefGoogle ScholarPubMed
Aung, M.H., Park, H.N., Han, M.K., Obertone, T.S., Abey, J., Aseem, F., Thule, P.M., Iuvone, P.M. & Pardue, M.T. (2014). Dopamine deficiency contributes to early visual dysfunction in a rodent model of type 1 diabetes. Journal of Neuroscience 34, 726–736.CrossRefGoogle Scholar
Baptista, F.I., Gaspar, J.M., Cristovao, A., Santos, P.F., Kofalvi, A. & Ambrosio, A.F. (2011). Diabetes induces early transient changes in the content of vesicular transporters and no major effects in neurotransmitter release in hippocampus and retina. Brain Research 1383, 257–269.CrossRefGoogle ScholarPubMed
Barber, A.J. & Baccouche, B. (2017). Neurodegeneration in diabetic retinopathy: Potential for novel therapies. Vision Research 139, 82–92.CrossRefGoogle ScholarPubMed
Bresnick, G.H. & Palta, M. (1987). Oscillatory potential amplitudes. Relation to severity of diabetic retinopathy. Archives of Ophthalmology 105, 929–933.CrossRefGoogle ScholarPubMed
Bronson-Castain, K.W., Bearse, M.A. Jr., Neuville, J., Jonasdottir, S., King-Hooper, B., Barez, S., Schneck, M.E. & Adams, A.J. (2012). Early neural and vascular changes in the adolescent type 1 and type 2 diabetic retina. Retina 32, 92–102.CrossRefGoogle ScholarPubMed
Brown, D.M., Heier, J.S., Clark, W.L., Boyer, D.S., Vitti, R., Berliner, A.J., Zeitz, O., Sandbrink, R., Zhu, X. & Haller, J.A. (2013). Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. American Journal of Ophthalmology 155, 429–437 e427.CrossRefGoogle ScholarPubMed
Calvo, E., Milla-Navarro, S., Ortuno-Lizaran, I., Gomez-Vicente, V., Cuenca, N., De la Villa, P. & Germain, F. (2020). Deleterious effect of NMDA plus kainate on the inner retinal cells and ganglion cell projection of the mouse. International Journal of Molecular Sciences 21, 1570.CrossRefGoogle ScholarPubMed
Castilho, A., Ambrosio, A.F., Hartveit, E. & Veruki, M.L. (2015a). Disruption of a neural microcircuit in the rod pathway of the mammalian retina by diabetes mellitus. Journal of Neuroscience 35, 5422–5433.CrossRefGoogle Scholar
Castilho, A., Madsen, E., Ambrosio, A.F., Veruki, M.L. & Hartveit, E. (2015b). Diabetic hyperglycemia reduces Ca2+ permeability of extrasynaptic AMPA receptors in AII amacrine cells. Journal of Neurophysiology 114, 1545–1553.CrossRefGoogle Scholar
Chakravarthy, H. & Devanathan, V. (2018). Molecular mechanisms mediating diabetic retinal neurodegeneration: Potential research avenues and therapeutic targets. Journal of Molecular Neuroscience 66, 445–461.CrossRefGoogle ScholarPubMed
Chavez, A.E., Grimes, W.N. & Diamond, J.S. (2010). Mechanisms underlying lateral GABAergic feedback onto rod bipolar cells in rat retina. Journal of Neuroscience 30, 2330–2339.CrossRefGoogle ScholarPubMed
Chen, Y., Li, J., Yan, Y. & Shen, X. (2016). Diabetic macular morphology changes may occur in the early stage of diabetes. BMC ophthalmology 16, 12.CrossRefGoogle ScholarPubMed
Coupland, S.G. (1987). A comparison of oscillatory potential and pattern electroretinogram measures in diabetic retinopathy. Documenta Ophthalmologica 66, 207–218.CrossRefGoogle ScholarPubMed
Cui, R.Z., Wang, L., Qiao, S.N., Wang, Y.C., Wang, X., Yuan, F., Weng, S.J., Yang, X.L. & Zhong, Y.M. (2019). ON-type retinal ganglion cells are preferentially affected in STZ-induced diabetic mice. Investigative Ophthalmology and Visual Science 60, 1644–1656.CrossRefGoogle ScholarPubMed
Dhamdhere, K.P., Bearse, M.A. Jr., Harrison, W., Barez, S., Schneck, M.E. & Adams, A.J. (2012). Associations between local retinal thickness and function in early diabetes. Investigative Ophthalmology and Visual Science 53, 6122–6128.CrossRefGoogle ScholarPubMed
Di Leo, M.A., Caputo, S., Falsini, B., Porciatti, V., Minnella, A., Greco, A.V. & Ghirlanda, G. (1992). Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes. Diabetes Care 15, 620–625.CrossRefGoogle ScholarPubMed
Diamond, J.S. (2017). Inhibitory interneurons in the retina: Types, circuitry, and function. Annual Review of Vision Science 3, 1–24.CrossRefGoogle ScholarPubMed
Dosso, A.A., Bonvin, E.R., Morel, Y., Golay, A., Assal, J.P. & Leuenberger, P.M. (1996). Risk factors associated with contrast sensitivity loss in diabetic patients. Graefe’s Archive for Clinical and Experimental Ophthalmology 234, 300–305.CrossRefGoogle ScholarPubMed
Eggers, E.D., Klein, J.S. & Moore-Dotson, J.M. (2013). Slow changes in Ca2(+) cause prolonged release from GABAergic retinal amacrine cells. Journal of Neurophysiology 110, 709–719.CrossRefGoogle ScholarPubMed
Eggers, E.D. & Lukasiewicz, P.D. (2006a). GABA(A), GABA(C) and glycine receptor-mediated inhibition differentially affects light-evoked signalling from mouse retinal rod bipolar cells. Journal of Physiology 572, 215–225.CrossRefGoogle Scholar
Eggers, E.D. & Lukasiewicz, P.D. (2006b). Receptor and transmitter release properties set the time course of retinal inhibition. Journal of Neuroscience 26, 9413–9425.CrossRefGoogle Scholar
El-Remessy, A.B., Al-Shabrawey, M., Khalifa, Y., Tsai, N.T., Caldwell, R.B. & Liou, G.I. (2006). Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. American Journal of Pathology 168, 235–244.CrossRefGoogle ScholarPubMed
Enzsoly, A., Szabo, A., Kantor, O., David, C., Szalay, P., Szabo, K., Szel, A., Nemeth, J. & Lukats, A. (2014). Pathologic alterations of the outer retina in streptozotocin-induced diabetes. Investigative Ophthalmology and Visual Science 55, 3686–3699.CrossRefGoogle ScholarPubMed
Enzsoly, A., Szabo, A., Szabo, K., Szel, A., Nemeth, J. & Lukats, A. (2015). Novel features of neurodegeneration in the inner retina of early diabetic rats. Histology and Histopathology 30, 11602.Google ScholarPubMed
Gagne, J., Milot, M., Gelinas, S., Lahsaini, A., Trudeau, F., Martinoli, M.G. & Massicotte, G. (1997). Binding properties of glutamate receptors in streptozotocin-induced diabetes in rats. Diabetes 46, 841–846.CrossRefGoogle ScholarPubMed
Gastinger, M.J., Kunselman, A.R., Conboy, E.E., Bronson, S.K. & Barber, A.J. (2008). Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice. Investigative Ophthalmology and Visual Science 49, 2635–2642.CrossRefGoogle ScholarPubMed
Gastinger, M.J., Singh, R.S. & Barber, A.J. (2006). Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. Investigative Ophthalmology and Visual Science 47, 3143–3150.CrossRefGoogle ScholarPubMed
Gleason, E., Borges, S. & Wilson, M. (1994). Control of transmitter release from retinal amacrine cells by Ca2+ influx and efflux. Neuron 13, 1109–1117.CrossRefGoogle ScholarPubMed
Gonzalez, V.H., Campbell, J., Holekamp, N.M., Kiss, S., Loewenstein, A., Augustin, A.J., Ma, J., Ho, A.C., Patel, V., Whitcup, S.M. & Dugel, P.U. (2016). Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: Analysis of protocol I data. American Journal of Ophthalmology 172, 72–79.CrossRefGoogle ScholarPubMed
Green, D.G. & Kapousta-Bruneau, N.V. (1999). A dissection of the electroretinogram from the isolated rat retina with microelectrodes and drugs. Visual Neuroscience 16, 727–741.CrossRefGoogle ScholarPubMed
Gu, L., Xu, H., Wang, F., Xu, G., Sinha, D., Wang, J., Xu, J.Y., Tian, H., Gao, F., Li, W., Lu, L., Zhang, J. & Xu, G.T. (2014). Erythropoietin exerts a neuroprotective function against glutamate neurotoxicity in experimental diabetic retina. Investigative Ophthalmology and Visual Science 55, 8208–8222.CrossRefGoogle ScholarPubMed
Gundogan, F.C., 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, 125–132.CrossRefGoogle ScholarPubMed
Harris, A., Arend, O., Danis, R.P., Evans, D., Wolf, S. & Martin, B.J. (1996). Hyperoxia improves contrast sensitivity in early diabetic retinopathy. British Journal of Ophthalmology 80, 209–213.CrossRefGoogle ScholarPubMed
Haverkamp, S. & Wassle, H. (2000). Immunocytochemical analysis of the mouse retina. Journal of Comparative Neurology 424, 1–23.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Heinze, L., Harvey, R.J., Haverkamp, S. & Wassle, H. (2007). Diversity of glycine receptors in the mouse retina: Localization of the alpha4 subunit. Journal of Comparative Neurology 500, 693–707.CrossRefGoogle ScholarPubMed
Heng, L.J., Yang, R.H. & Jia, D. (2011). Diabetes impairs learning performance through affecting membrane excitability of hippocampal pyramidal neurons. Behavioural Brain Research 224, 250–258.CrossRefGoogle ScholarPubMed
Hernandez, C., Bogdanov, P., Corraliza, L., Garcia-Ramirez, M., Sola-Adell, C., Arranz, J.A., Arroba, A.I., Valverde, A.M. & Simo, R. (2016a). Topical administration of GLP-1 receptor agonists prevents retinal neurodegeneration in experimental diabetes. Diabetes 65, 172–187.Google Scholar
Hernandez, C., Dal Monte, M., Simo, R. & Casini, G. (2016b). Neuroprotection as a therapeutic target for diabetic retinopathy. Journal of Diabetes Research 2016, 9508541.CrossRefGoogle Scholar
Hernandez, C., Garcia-Ramirez, M., Corraliza, L., Fernandez-Carneado, J., Farrera-Sinfreu, J., Ponsati, B., Gonzalez-Rodriguez, A., Valverde, A.M. & Simo, R. (2013). Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes. Diabetes 62, 2569–2578.CrossRefGoogle ScholarPubMed
Herrmann, R., Heflin, S.J., Hammond, T., Lee, B., Wang, J., Gainetdinov, R.R., Caron, M.G., Eggers, E.D., Frishman, L.J., McCall, M.A. & Arshavsky, V.Y. (2011). Rod vision is controlled by dopamine-dependent sensitization of rod bipolar cells by GABA. Neuron 72, 101–110.CrossRefGoogle ScholarPubMed
Hombrebueno, J.R., Chen, M., Penalva, R.G. & 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.CrossRefGoogle ScholarPubMed
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 Journal of Medical Sciences 44, 1–8.Google ScholarPubMed
Hood, D.C., Frishman, L.J., Saszik, S. & Viswanathan, S. (2002). Retinal origins of the primate multifocal ERG: Implications for the human response. Investigative Ophthalmology and Visual Science 43, 1673–1685.Google ScholarPubMed
Ishikawa, A., Ishiguro, S. & Tamai, M. (1996). Changes in GABA metabolism in streptozotocin-induced diabetic rat retinas. Current Eye Research 15, 63–71.CrossRefGoogle ScholarPubMed
Jackson, C.R., Ruan, G.X., Aseem, F., Abey, J., Gamble, K., Stanwood, G., Palmiter, R.D., Iuvone, P.M. & McMahon, D.G. (2012). Retinal dopamine mediates multiple dimensions of light-adapted vision. Journal of Neuroscience 32, 9359–9368.CrossRefGoogle ScholarPubMed
Jaffe, G.J. & Caprioli, J. (2004). Optical coherence tomography to detect and manage retinal disease and glaucoma. American Journal of Ophthalmology 137, 156–169.CrossRefGoogle ScholarPubMed
Jeon, C.J., Strettoi, E. & Masland, R.H. (1998). The major cell populations of the mouse retina. Journal of Neuroscience 18, 8936–8946.CrossRefGoogle ScholarPubMed
Juen, S. & Kieselbach, G.F. (1990). Electrophysiological changes in juvenile diabetics without retinopathy. Archives of Ophthalmology 108, 372–375.CrossRefGoogle ScholarPubMed
Karti, O., Nalbantoglu, O., Abali, S., Ayhan, Z., Tunc, S., Kusbeci, T. & Ozkan, B. (2017). Retinal ganglion cell loss in children with type 1 diabetes mellitus without diabetic retinopathy. Ophthalmic Surgery, Lasers and Imaging Retina 48, 473–477.CrossRefGoogle ScholarPubMed
Katz, G., Levkovitch-Verbin, H., Treister, G., Belkin, M., Ilany, J. & Polat, U. (2010). Mesopic foveal contrast sensitivity is impaired in diabetic patients without retinopathy. Graefes Archive For Clinical and Experimental Ophthalmology 248, 1699–1703.CrossRefGoogle ScholarPubMed
Kim, M.K., Aung, M.H., Mees, L., Olson, D.E., Pozdeyev, N., Iuvone, P.M., Thule, P.M. & Pardue, M.T. (2018). Dopamine deficiency mediates early rod-driven inner retinal dysfunction in diabetic mice. Investigative Ophthalmology and Visual Science 59, 572–581.CrossRefGoogle ScholarPubMed
Kirwin, S.J., Kanaly, S.T., Hansen, C.R., Cairns, B.J., Ren, M. & Edelman, J.L. (2011). Retinal gene expression and visually evoked behavior in diabetic long evans rats. Investigative Ophthalmology and Visual Science 52, 7654–7663.CrossRefGoogle ScholarPubMed
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. Japanese Journal of Ophthalmology 50, 367–373.CrossRefGoogle ScholarPubMed
Kohzaki, K., Vingrys, A.J. & Bui, B.V. (2008). Early inner retinal dysfunction in streptozotocin-induced diabetic rats. Investigative Ophthalmology and Visual Science 49, 3595–3604.CrossRefGoogle ScholarPubMed
Kowluru, R.A., Engerman, R.L., Case, G.L. & Kern, T.S. (2001). Retinal glutamate in diabetes and effect of antioxidants. Neurochemistry International 38, 385–390.CrossRefGoogle ScholarPubMed
Kur, J., Burian, M.A. & Newman, E.A. (2016). Light adaptation does not prevent early retinal abnormalities in diabetic rats. Scientific Reports 6, 21075.CrossRefGoogle Scholar
Lahouaoui, H., Coutanson, C., Cooper, H.M., Bennis, M. & Dkhissi-Benyahya, O. (2016). Diabetic retinopathy alters light-induced clock gene expression and dopamine levels in the mouse retina. Molecular Vision 22, 959–969.Google ScholarPubMed
Laron, M., Bearse, M.A. Jr., Bronson-Castain, K., Jonasdottir, S., King-Hooper, B., Barez, S., Schneck, M.E. & Adams, A.J. (2012). Association between local neuroretinal function and control of adolescent type 1 diabetes. Investigative Ophthalmology and Visual Science 53, 7071–7076.CrossRefGoogle ScholarPubMed
Lau, J.C., Kroes, R.A., Moskal, J.R. & Linsenmeier, R.A. (2013). Diabetes changes expression of genes related to glutamate neurotransmission and transport in the Long-Evans rat retina. Molecular Vision 19, 1538–1553.Google ScholarPubMed
Layton, C.J., Safa, R. & Osborne, N.N. (2007). Oscillatory potentials and the b-wave: Partial masking and interdependence in dark adaptation and diabetes in the rat. Graefes Archive for Clinical and Experimental Ophthalmology 245, 1335–1345.CrossRefGoogle ScholarPubMed
Lee, S.E., Han, K., Baek, J.Y., Ko, K.S., Lee, K.U., Koh, E.H & Taskforce Team for Diabetes Fact Sheet of the Korean Diabetes A. (2018a). Association between diabetic retinopathy and Parkinson disease: The Korean national health insurance service database. Journal of Clinical Endocrinology and Metabolism 103, 3231–3238.CrossRefGoogle Scholar
Lee, V.K., Hosking, B.M., Holeniewska, J., Kubala, E.C., von Leithner, P.L., Gardner, P.J., Foxton, R.H. & Shima, D.T. (2018b). BTBR ob/ob mouse model of type 2 diabetes exhibits early loss of retinal function and retinal inflammation followed by late vascular changes. Diabetologia 61, 2422–2432.CrossRefGoogle Scholar
Li, J., Chen, P., Bao, Y., Sun, Y., He, J. & Liu, X. (2019). PET imaging of vesicular monoamine transporter 2 in early diabetic retinopathy using [(18)F]FP-(+)-DTBZ. Molecular Imaging and Biology. https://pubmed.ncbi.nlm.nih.gov/31650482/Google Scholar
Li, W., Wang, P. & Li, H. (2014). Upregulation of glutamatergic transmission in anterior cingulate cortex in the diabetic rats with neuropathic pain. Neuroscience Letters 568, 29–34.CrossRefGoogle ScholarPubMed
Lieth, E., Barber, A.J., Xu, B., Dice, C., Ratz, M.J., Tanase, D. & Strother, J.M. (1998). Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. Diabetes 47, 815–820.CrossRefGoogle ScholarPubMed
Liu, F., Saul, A.B., Pichavaram, P., Xu, Z., Rudraraju, M., Somanath, P.R., Smith, S.B., Caldwell, R.B. & Narayanan, S.P.. (2020). Pharmacological inhibition of spermine oxidase reduces neurodegeneration and improves retinal function in diabetic mice. Journal of Clinical Medicine 9, 340.CrossRefGoogle ScholarPubMed
Liu, J., Tu, H., Zheng, H., Zhang, L., Tran, T.P., Muelleman, R.L. & Li, Y.L. (2012). Alterations of calcium channels and cell excitability in intracardiac ganglion neurons from type 2 diabetic rats. American Journal of Physiology-Cell Physiology 302, C1119–1127.CrossRefGoogle ScholarPubMed
de Faria, J.M.L., Katsumi, O., Cagliero, E., Nathan, D. & Hirose, T. (2001). Neurovisual abnormalities preceding the retinopathy in patients with long-term type 1 diabetes mellitus. Graefes Archive for Clinical and Experimental Ophthalmology 239, 643–648.CrossRefGoogle Scholar
de Faria, J.M.L., Russ, H. & Costa, V.P. (2002). Retinal nerve fibre layer loss in patients with type 1 diabetes mellitus without retinopathy. British Journal of Ophthalmology 86, 725–728.CrossRefGoogle Scholar
Luo, X. & Frishman, L.J. (2011). Retinal pathway origins of the pattern electroretinogram (PERG). Investigative Ophthalmology and Visual Science 52, 8571–8584.CrossRefGoogle Scholar
Luu, C.D., Szental, J.A., Lee, S.Y., Lavanya, R. & Wong, T.Y. (2010). Correlation between retinal oscillatory potentials and retinal vascular caliber in type 2 diabetes. Investigative Ophthalmology and Visual Science 51, 482–486.CrossRefGoogle ScholarPubMed
Ly, A., Scheerer, M.F., Zukunft, S., Muschet, C., Merl, J., Adamski, J., de Angelis, M.H., Neschen, S., Hauck, S.M. & Ueffing, M. (2014). Retinal proteome alterations in a mouse model of type 2 diabetes. Diabetologia 57, 192–203.CrossRefGoogle Scholar
Lynch, S.K. & Abramoff, M.D. (2017). Diabetic retinopathy is a neurodegenerative disorder. Vision Research 139, 101–107.CrossRefGoogle ScholarPubMed
Martin, P.M., Roon, P., Van Ells, T.K., Ganapathy, V. & Smith, S.B. (2004). Death of retinal neurons in streptozotocin-induced diabetic mice. Investigative Ophthalmology and Visual Science 45, 3330–3336.CrossRefGoogle ScholarPubMed
McCall, M.A., Lukasiewicz, P.D., Gregg, R.G. & Peachey, N.S. (2002). Elimination of the r1 subunit abolishes GABAC receptor expression and alters visual processing in the mouse retina. Journal of Neuroscience 22, 4163–4174.CrossRefGoogle Scholar
McFarlane, M., Wright, T., Stephens, D., Nilsson, J. & Westall, C.A. (2012). Blue flash ERG PhNR changes associated with poor long-term glycemic control in adolescents with type 1 diabetes. Investigative Ophthalmology and Visual Science 53, 741–748.CrossRefGoogle ScholarPubMed
Miller, W.P., Yang, C., Mihailescu, M.L., Moore, J.A., Dai, W., Barber, A.J. & Dennis, M.D. (2018). Deletion of the Akt/mTORC1 repressor REDD1 prevents visual dysfunction in a rodent model of type 1 diabetes. Diabetes 67, 110–119.CrossRefGoogle Scholar
Moller, A. & Eysteinsson, T. (2003). Modulation of the components of the rat dark-adapted electroretinogram by the three subtypes of GABA receptors. Visual Neuroscience 20, 535–542.CrossRefGoogle ScholarPubMed
Moore-Dotson, J.M., Beckman, J.J., Mazade, R.E., Hoon, M., Bernstein, A.S., Romero-Aleshire., M.J., Brooks, H.L. & Eggers, E.D. (2016). Early retinal neuronal dysfunction in diabetic mice: Reduced light-evoked inhibition increases rod pathway signaling. Investigative Ophthalmology and Visual Science 57, 1418–1430.CrossRefGoogle ScholarPubMed
Moore-Dotson, J.M. & Eggers, E.D. (2019). Reductions in calcium signaling limit inhibition to diabetic retinal rod bipolar cells. Investigative Ophthalmology and Visual Science 60, 4063–4073.CrossRefGoogle ScholarPubMed
Morales-Calixto, E., Velazquez-Flores, M.A., Sanchez-Chavez, G., Ruiz Esparza-Garrido, R. & Salceda, R. (2019). Glycine receptor is differentially expressed in the rat retina at early stages of streptozotocin-induced diabetes. Neuroscience Letters 712, 134506.CrossRefGoogle ScholarPubMed
Morgado, C., Pinto-Ribeiro, F. & Tavares, I. (2008). Diabetes affects the expression of GABA and potassium chloride cotransporter in the spinal cord: A study in streptozotocin diabetic rats. Neuroscience Letters 438, 102–106.CrossRefGoogle ScholarPubMed
Motz, C.T., Chesler, K.C., Allen, R.S., Bales, K.L., Mees, L.M., Feola, A.J., Maa, A.Y., Olson, D.E., Thule, P.M., Iuvone, P.M., Hendrick, A.M. & Pardue, M.T. (2020). Novel detection and restorative levodopa treatment for preclinical diabetic retinopathy. Diabetes 69, 1518–1527.CrossRefGoogle ScholarPubMed
Naarendorp, F. & Sieving, P.A. (1991). The scotopic threshold response of the cat ERG is suppressed selectively by GABA and glycine. Vision Research 31, 1–15.CrossRefGoogle ScholarPubMed
Nguyen, Q.D., Brown, D.M., Marcus, D.M., Boyer, D.S., Patel, S., Feiner, L., Gibson, A., Sy, J., Rundle, A.C., Hopkins, J.J., Rubio, R.G., Ehrlich, J.S., Rise & Group RR. (2012). Ranibizumab for diabetic macular edema: Results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119, 789–801.CrossRefGoogle Scholar
Nishimura, C. & Kuriyama, K. (1985). Alterations in the retinal dopaminergic neuronal system in rats with streptozotocin-induced diabetes. Journal of Neurochemistry 45, 448–455.CrossRefGoogle ScholarPubMed
Ola, M.S., Nawaz, M.I., Khan, H.A. & Alhomida, A.S. (2013). Neurodegeneration and neuroprotection in diabetic retinopathy. International Journal of Molecular Sciences 14, 2559–2572.CrossRefGoogle ScholarPubMed
Osaadon, P., Fagan, X.J., Lifshitz, T. & Levy, J. (2014). A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye (London) 28, 510–520.CrossRefGoogle ScholarPubMed
Pardue, M.T., Barnes, C.S., Kim, M.K., Aung, M.H., Amarnath, R., Olson, D.E. & Thule, P.M. (2014). Rodent hyperglycemia-induced inner retinal deficits are mirrored in human diabetes. Translational Vision Science and Technology 3, 6.CrossRefGoogle ScholarPubMed
Parisi, V. & Uccioli, L. (2001). Visual electrophysiological responses in persons with type 1 diabetes. Diabetes/Metabolism Research and Reviews 17, 12–18.CrossRefGoogle ScholarPubMed
Parisi, V., Uccioli, L., Monticone, G., Parisi, L., Manni, G., Ippoliti, D., Menzinger, G. & Bucci, M.G. (1997). Electrophysiological assessment of visual function in IDDM patients. Electroencephalography and Clinical Neurophysiology 104, 171–179.CrossRefGoogle ScholarPubMed
Park, H.Y., Kim, I.T. & Park, C.K. (2011). Early diabetic changes in the nerve fibre layer at the macula detected by spectral domain optical coherence tomography. British Journal of Ophthalmology 95, 1223–1228.CrossRefGoogle ScholarPubMed
Pinilla, I., Idoipe, M., Perdices, L., Sanchez-Cano, A., Acha, J., Lopez-Galvez, M.I., Cuenca, N., Abecia, E. & Orduna-Hospital, E. (2020). Changes in total and inner retinal thicknesses in type 1 diabetes with no retinopathy after 8 years of follow-up. Retina 40, 1379–1386.CrossRefGoogle ScholarPubMed
Pulido, J.E., Pulido, J.S., Erie, J.C., Arroyo, J., Bertram, K., Lu, M.J. & Shippy, S.A. (2007). A role for excitatory amino acids in diabetic eye disease. Experimental Diabetes Research 2007, 36150.CrossRefGoogle ScholarPubMed
Ramsey, D.J., Ripps, H. & Qian, H. (2006). An electrophysiological study of retinal function in the diabetic female rat. Investigative Ophthalmology and Visual Science 47, 5116–5124.CrossRefGoogle ScholarPubMed
Robson, J.G. & Frishman, L.J. (1998). Dissecting the dark-adapted electroretinogram. Documenta Ophthalmologica 95, 187–215.CrossRefGoogle ScholarPubMed
Robson, J.G., Maeda, H., Saszik, S.M. & Frishman, L.J. (2004). In vivo studies of signaling in rod pathways of the mouse using the electroretinogram. Vision Research 44, 3253–3268.CrossRefGoogle ScholarPubMed
Safi, S., Rahimi, A., Raeesi, A., Safi, H., Amiri, M.A., Malek, M., Yaseri, M., Haeri, M., Middleton, F.A., Solessio, E. & Ahmadieh, H. (2017). Contrast sensitivity to spatial gratings in moderate and dim light conditions in patients with diabetes in the absence of diabetic retinopathy. BMJ Open Diabetes Research and Care 5, e000408.CrossRefGoogle ScholarPubMed
Santiago, A.R., Gaspar, J.M., Baptista, F.I., Cristovao, A.J., Santos, P.F., Kamphuis, W. & Ambrosio, A.F. (2009). Diabetes changes the levels of ionotropic glutamate receptors in the rat retina. Molecular Vision 15, 1620–1630.Google ScholarPubMed
Schmidt-Erfurth, U., Chong, V., Loewenstein, A., Larsen, M., Souied, E., Schlingemann, R., Eldem, B., Mones, J., Richard, G., Bandello, F. & European Society of Retina Specialists. (2014). Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). British Journal of Ophthalmology 98, 1144–1167.CrossRefGoogle Scholar
Scuderi, S., D’Amico, A.G., Castorina, A., Federico, C., Marrazzo, G., Drago, F., Bucolo, C. & D’Agata, V. (2014). Davunetide (NAP) protects the retina against early diabetic injury by reducing apoptotic death. Journal of Molecular Neuroscience 54, 395–404.CrossRefGoogle ScholarPubMed
Seki, M., Tanaka, T., Nawa, H., Usui, T., Fukuchi, T., Ikeda, K., Abe, H. & Takei, N. (2004). Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: Therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells. Diabetes 53, 2412–2419.CrossRefGoogle ScholarPubMed
Semkova, I., Huemmeke, M., Ho, M.S., Merkl, B., Abari, E., Paulsson, M., Joussen, A.M. & Plomann, M. (2010). Retinal localization of the glutamate receptor GluR2 and GluR2-regulating proteins in diabetic rats. Experimental Eye Research 90, 244–253.CrossRefGoogle ScholarPubMed
Sergeys, J., Etienne, I., Van Hove, I., Lefevere, E., Stalmans, I., Feyen, J.H.M., Moons, L. & Van Bergen, T. (2019). Longitudinal in vivo characterization of the streptozotocin-induced diabetic mouse model: Focus on early inner retinal responses. Investigative Ophthalmology and Visual Science 60, 807–822.CrossRefGoogle ScholarPubMed
Shinoda, K., Rejdak, R., Schuettauf, F., Blatsios, G., Volker, M., Tanimoto, N., Olcay, T., Gekeler, F., Lehaci, C., Naskar, R., Zagorski, Z. & Zrenner, E. (2007). Early electroretinographic features of streptozotocin-induced diabetic retinopathy. Clinical & Experimental Ophthalmology 35, 847–854.CrossRefGoogle ScholarPubMed
Simonsen, S.E. (1980). The value of the oscillatory potential in selecting juvenile diabetics at risk of developing proliferative retinopathy. Acta ophthalmologica (Copenhagen) 58, 865–878.CrossRefGoogle ScholarPubMed
Singer, J.H., Lassova, L., Vardi, N. & Diamond, J.S. (2004). Coordinated multivesicular release at a mammalian ribbon synapse. Nature Neuroscience 7, 826–833.CrossRefGoogle Scholar
Smith, B.J., Cote, P.D. & Tremblay, F. (2015). Dopamine modulation of rod pathway signaling by suppression of GABAC feedback to rod-driven depolarizing bipolar cells. European Journal of Neuroscience 42, 2258–2270.CrossRefGoogle ScholarPubMed
Szabadfi, K., Atlasz, T., Kiss, P., Reglodi, D., Szabo, A., Kovacs, K., Szalontai, B., Setalo, G. Jr., Banki, E., Csanaky, K., Tamas, A. & Gabriel, R. (2012). Protective effects of the neuropeptide PACAP in diabetic retinopathy. Cell Tissue Research 348, 37–46.CrossRefGoogle ScholarPubMed
Travis, A.M., Heflin, S.J., Hirano, A.A., Brecha, N.C. & Arshavsky, V.Y. (2018). Dopamine-dependent sensitization of rod bipolar cells by GABA is conveyed through wide-field amacrine cells. Journal of Neuroscience 38, 723–732.CrossRefGoogle ScholarPubMed
Vadala, M., Anastasi, M., Lodato, G. & Cillino, S. (2002). Electroretinographic oscillatory potentials in insulin-dependent diabetes patients: A long-term follow-up. Acta Ophthalmologica Scandinavica 80, 305–309.CrossRefGoogle ScholarPubMed
Van Dijk, H.W., Verbraak, F.D., Kok, P.H., Garvin, M.K., Sonka, M., Lee, K., Devries, J.H., Michels, R.P., van Velthoven, M.E., Schlingemann, R.O. & Abramoff, M.D. (2010). Decreased retinal ganglion cell layer thickness in type 1 diabetic patients. Investigative Ophthalmology and Visual Science 51, 3660–3665.CrossRefGoogle Scholar
VanGuilder, H.D., Brucklacher, R.M., Patel, K., Ellis, R.W., Freeman, W.M. & Barber, A.J. (2008). Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina. European Journal of Neuroscience 28, 1–11.CrossRefGoogle ScholarPubMed
Verma, A., Raman, R., Vaitheeswaran, K., Pal, S.S., Laxmi, G., Gupta, M., Shekar, S.C. & Sharma., T. (2012). Does neuronal damage precede vascular damage in subjects with type 2 diabetes mellitus and having no clinical diabetic retinopathy? Ophthalmic Research 47, 202–207.CrossRefGoogle ScholarPubMed
Viswanathan, S., Frishman, L.J., Robson, J.G., Harwerth, R.S. & Smith, E.L., 3rd. (1999). The photopic negative response of the macaque electroretinogram: Reduction by experimental glaucoma. Investigative Ophthalmology and Visual Science 40, 1124–1136.Google ScholarPubMed
Wachtmeister, L. (1980). Further studies of the chemical sensitivity of the oscillatory potentials of the electroretinogram (ERG) I GABA- and glycine antagonists. Acta Ophthalmol (Copenh) 58, 712–725.CrossRefGoogle ScholarPubMed
Wachtmeister, L. & Dowling, J.E. (1978). The oscillatory potentials of the mudpuppy retina. Investigative Ophthalmology and Visual Science 17, 1176–1188.Google ScholarPubMed
Witkovsky, P. (2004). Dopamine and retinal function. Documenta Ophthalmologica 108, 17–40.CrossRefGoogle ScholarPubMed
Yang, S., Zhao, J. & Sun, X. (2016). Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: A comprehensive review. Drug Design, Development and Therapy 10, 1857–1867.Google ScholarPubMed
Yang, Y., Mao, D., Chen, X., Zhao, L., Tian, Q., Liu, C. & Zhou, B.L. (2012). Decrease in retinal neuronal cells in streptozotocin-induced diabetic mice. Molecular Vision 18, 1411–1420.Google ScholarPubMed
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, 1266–1271.CrossRefGoogle ScholarPubMed
Yu, J., Wang, L., Weng, S.J., Yang, X.L., Zhang, D.Q. & Zhong, Y.M. (2013). Hyperactivity of ON-type retinal ganglion cells in streptozotocin-induced diabetic mice. PLoS One 8, e76049.CrossRefGoogle ScholarPubMed
Zeng, X.X., Ng, Y.K. & Ling, E.A. (2000). Neuronal and microglial response in the retina of streptozotocin-induced diabetic rats. Vision Neuroscience 17, 463–471.CrossRefGoogle ScholarPubMed
Zhang, Y., Zhang, J., Wang, Q., Lei, X., Chu, Q., Xu, G.T. & Ye, W. (2011). Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats. Investigative Ophthalmology and Visual Science 52, 278–285.CrossRefGoogle ScholarPubMed
Zherebitskaya, E., Schapansky, J., Akude, E., Smith, D.R., Van der Ploeg, R., Solovyova, N., Verkhratsky, A. & Fernyhough, P. (2012). Sensory neurons derived from diabetic rats have diminished internal Ca2+ stores linked to impaired re-uptake by the endoplasmic reticulum. ASN Neuro 4(1):e00072.CrossRefGoogle ScholarPubMed