Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-13T02:59:44.024Z Has data issue: false hasContentIssue false
  • English
  • Français

Preventing diabetic retinopathy by mitigating subretinal space oxidative stress in vivo

Published online by Cambridge University Press:  15 June 2020

Bruce A. Berkowitz
Bruce A. Berkowitz*
Affiliation:
Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan
*
*Bruce A. Berkowitz, E-mail: baberko@med.wayne.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Patients with diabetes continue to suffer from impaired visual performance before the appearance of overt damage to the retinal microvasculature and later sight-threatening complications. This diabetic retinopathy (DR) has long been thought to start with endothelial cell oxidative stress. Yet newer data surprisingly finds that the avascular outer retina is the primary site of oxidative stress before microvascular histopathology in experimental DR. Importantly, correcting this early oxidative stress is sufficient to restore vision and mitigate the histopathology in diabetic models. However, translating these promising results into the clinic has been stymied by an absence of methods that can measure and optimize anti-oxidant treatment efficacy in vivo. Here, we review imaging approaches that address this problem. In particular, diabetes-induced oxidative stress impairs dark–light regulation of subretinal space hydration, which regulates the distribution of interphotoreceptor binding protein (IRBP). IRBP is a vision-critical, anti-oxidant, lipid transporter, and pro-survival factor. We show how optical coherence tomography can measure subretinal space oxidative stress thus setting the stage for personalizing anti-oxidant treatment and prevention of impactful declines and loss of vision in patients with diabetes.

Keywords

MRIOCTL-type calcium channelsretinadiffusion MRIfree radicalsphotoreceptors
Type
Review Article
Information
Visual Neuroscience , Volume 37 , 2020 , E002
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

Adams, A.J. & Bearse, M.A. Jr. (2012). Retinal neuropathy precedes vasculopathy in diabetes: a function-based opportunity for early treatment intervention? Clinical and Experimental Optometry 95, 256–265.CrossRefGoogle ScholarPubMed
Adijanto, J., Banzon, T., Jalickee, S., Wang, N.S., & Miller, S.S. (2009). CO2-induced ion and fluid transport in human retinal pigment epithelium. The Journal of General Physiology 133, 603–622.CrossRefGoogle ScholarPubMed
Aredo, B., Li, T., Chen, X., Zhang, K., Wang, C.X., Gou, D., Zhao, B., He, Y., & Ufret-Vincenty, R.L. (2015). A chimeric Cfh transgene leads to increased retinal oxidative stress, inflammation, and accumulation of activated subretinal microglia in mice. Investigative Ophthalmology & Visual Science 56, 3427–3440.CrossRefGoogle ScholarPubMed
Aung, M.H., H.N., Park, 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
Baumann, L., Gerstner, A., Zong, X., Biel, M., & Wahl-Schott, C. (2004). Functional characterization of the L-type Ca2+ channel Cav1.4+¦1 from mouse retina. Investigative Ophthalmology & Visual Science 45, 708–713.CrossRefGoogle ScholarPubMed
Berkowitz, B.A. (2006). Noninvasive and simultaneous imaging of layer-specific retinal functional adaptation by manganese-enhanced MRI. Investigative Ophthalmology & Visual Science 47, 2668–2674.CrossRefGoogle ScholarPubMed
Berkowitz, B.A. (2011). Intraretinal calcium channels and retinal morbidity in experimental retinopathy of prematurity. Neuroimage 17, 2516–2526.Google ScholarPubMed
Berkowitz, B.A. (2018). Oxidative stress measured in vivo without an exogenous contrast agent using QUEST MRI. Journal of Magnetic Resonance 291, 94–100.CrossRefGoogle ScholarPubMed
Berkowitz, B.A., Bissig, D., Patel, P., Bhatia, A., & Roberts, R. (2012). Acute systemic 11-cis-retinal intervention improves abnormal outer retinal ion channel closure in diabetic mice. Molecular Vision 18, 372–376.Google ScholarPubMed
Berkowitz, B.A., Bissig, D., & Roberts, R. (2016a). MRI of rod cell compartment-specific function in disease and treatment in vivo. Progress in Retinal and Eye Research 51, 90–106.CrossRefGoogle Scholar
Berkowitz, B.A., Bredell, B.X., Davis, C., Samardzija, M., Grimm, C., & Roberts, R. (2015a). Measuring in vivo free radical production by the outer retina. Investigative Ophthalmology & Visual Science 56, 7931–7938.CrossRefGoogle Scholar
Berkowitz, B.A., Gradianu, M., Bissig, D., Kern, T.S., & Roberts, R. (2009a). Retinal ion regulation in a mouse model of diabetic retinopathy: Natural history and the effect of Cu/Zn superoxide dismutase overexpression. Investigative Ophthalmology Visual Science 50, 2351–2358.CrossRefGoogle Scholar
Berkowitz, B.A., Grady, E.M., Khetarpal, N., Patel, A., & Roberts, R. (2015b). Oxidative stress and light-evoked responses of the posterior segment in a mouse model of diabetic retinopathy. Investigative Ophthalmology Visual Science 56, 606–615.CrossRefGoogle Scholar
Berkowitz, B.A., Kern, T.S., Bissig, D., Patel, P., Bhatia, A., Kefalov, V.J., & Roberts, R. (2015c). Systemic retinaldehyde treatment corrects retinal oxidative stress, rod dysfunction, and impaired visual performance in diabetic micesystemic retinaldehyde treatment in diabetic mice. Investigative Ophthalmology & Visual Science 56, 6294–6303.CrossRefGoogle Scholar
Berkowitz, B.A., Lewin, A.S., Biswal, M.R., Bredell, B.X., Davis, C., & Roberts, R. (2016b). MRI of retinal free radical production with laminar resolution in vivo. Investigative Ophthalmology & Visual Science 57, 577–585.CrossRefGoogle Scholar
Berkowitz, B.A., Murphy, G.G., Craft, C.M., Surmeier, D.J., & Roberts, R. (2015d). Genetic dissection of horizontal cell inhibitory signaling in mice in complete darkness in vivo. Investigative Ophthalmology & Visual Science 56, 3132–3139.CrossRefGoogle Scholar
Berkowitz, B.A., Olds, H.K., Richards, C., Joy, J., Rosales, T., Podolsky, R.H., Childers, K.L., Hubbard, W.B., Sullivan, P.G., Gao, S., Li, Y., Qian, H., & Roberts, R. (2020). Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo. PLOS ONE 15, e0226840.CrossRefGoogle ScholarPubMed
Berkowitz, B.A., Podolsky, R.H., Farrell, B., Lee, H., Trepanier, C., Berri, A.M., Dernay, K., Graffice, E., Shafie-Khorassani, F., Kern, T.S., & Roberts, R. (2018a). D-cis-diltiazem can produce oxidative stress in healthy depolarized rods in vivo. Investigative Ophthalmology & Visual Science 59, 2999–3010.CrossRefGoogle Scholar
Berkowitz, B.A., Podolsky, R.H., Lenning, J., Khetarpal, N., Tran, C., Wu, J.Y., Berri, A.M., Dernay, K., Shafie-Khorassani, F., & Roberts, R. (2017). Sodium iodate produces a strain-dependent retinal oxidative stress response measured in vivo using QUEST MRI. Investigative Ophthalmology & Visual Science 58, 3286–3293.CrossRefGoogle ScholarPubMed
Berkowitz, B.A., Podolsky, R.H., Lins-Childers, K.M., Li, Y., & Qian, H. (2019). Outer retinal oxidative stress measured in vivo using QUEnch-assiSTed (QUEST) OCT. Investigative Ophthalmology & Visual Science 60 1566–1570.CrossRefGoogle ScholarPubMed
Berkowitz, B.A., Podolsky, R.H., Qian, H., Li, Y., Jiang, K., Nellissery, J., Swaroop, A., & Roberts, R. (2018b). Mitochondrial respiration in outer retina contributes to light-evoked increase in hydration in vivo. Investigative Ophthalmology & Visual Science 59, 5957–5964.CrossRefGoogle Scholar
Berkowitz, B.A., Roberts, R., Oleske, D.A., Chang, M., Schafer, S., Bissig, D., & Gradianu, M. (2008). Quantitative mapping of ion channel regulation by visual cycle activity in rodent photoreceptors in vivo. Investigative Ophthalmology Visual Science. 2009 50:1880–5.CrossRefGoogle ScholarPubMed
Berkowitz, B.A., Roberts, R., Oleske, D.A., Chang, M., Schafer, S., Bissig, D., & Gradianu, M. (2009b). Quantitative mapping of ion channel regulation by visual cycle activity in rodent photoreceptors in vivo. Investigative Ophthalmology & Visual Science 50, 1880–1885.CrossRefGoogle Scholar
Berkowitz, B.A., Roberts, R., Stemmler, A., Luan, H., & Gradianu, M. (2007). Impaired apparent ion demand in experimental diabetic retinopathy: Correction by lipoic acid. Investigative Ophthalmology & Visual Science 48, 4753–4758.CrossRefGoogle ScholarPubMed
Berkowitz, B.A., Schmidt, T., Podolsky, R.H., & Roberts, R. (2016c). Melanopsin phototransduction contributes to light-evoked choroidal expansion and rod L-type calcium channel function in vivomelanopsin and choroid regulation. Investigative Ophthalmology & Visual Science 57, 5314–5319.CrossRefGoogle Scholar
Berkowitz, B.A., Wen, X., Thoreson, W.B., Kern, T.S., & Roberts, R. (2015e). Abnormal rod calcium homeostasis and the development of retinal oxidative stress in diabetes. Investigative Ophthalmology & Visual Science 56, 4280–4280.Google Scholar
Bhatwadekar, A.D., Duan, Y., Korah, M., Thinschmidt, J.S., Hu, P., Leley, S.P., Caballero, S., Shaw, L., Busik, J., & Grant, M.B. (2017). Hematopoietic stem/progenitor involvement in retinal microvascular repair during diabetes: Implications for bone marrow rejuvenation. Vision Research 139, 211–220.CrossRefGoogle ScholarPubMed
Bissig, D. & Berkowitz, B.A. (2012). Light-dependent changes in outer retinal water diffusion in rats in vivo. Molecular Vision 18, 2561–2562.Google ScholarPubMed
Carlson, R.O., Masco, D., Brooker, G., & Spiegel, S. (1994). Endogenous ganglioside GM1 modulates L-type calcium channel activity in N18 neuroblastoma cells. The Journal of Neuroscience 14, 2272–2281.CrossRefGoogle ScholarPubMed
Carter-Dawson, L.D., Lavail, M.M., & Sidman, R.L. (1978). Differential effect of the rd mutation on rods and cones in the mouse retina. Investigative Ophthalmology Visual Science 17, 489–498.Google ScholarPubMed
Chen, C., Adler, L., Goletz, P., Gonzalez-Fernandez, F., Thompson, D.A., & Koutalos, Y. (2017). Interphotoreceptor retinoid–binding protein removes all-trans-retinol and retinal from rod outer segments, preventing lipofuscin precursor formation. Journal of Biological Chemistry 292, 19356–19365.CrossRefGoogle ScholarPubMed
Colantuoni, A., Longoni, B., & Marchiafava, P.L. (2002). Retinal photoreceptors of Syrian hamsters undergo oxidative stress during streptozotocin-induced diabetes. Diabetologia 45, 121–124.CrossRefGoogle ScholarPubMed
Combadiere, C., Feumi, C., Raoul, W., Keller, N., Rodero, M., Pezard, A., Lavalette, S., Houssier, M., Jonet, L., Picard, E., Debre, P., Sirinyan, M., Deterre, P., Ferroukhi, T., Cohen, S.Y., Chauvaud, D., Jeanny, J.C., Chemtob, S., Behar-Cohen, F., & Sennlaub, F. (2007). CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. Journal of Clinical Investigation. 2007 117:2920–8CrossRefGoogle ScholarPubMed
Davies, M.H., Eubanks, J.P., & Powers, M.R. (2006). Microglia and macrophages are increased in response to ischemia-induced retinopathy in the mouse retina. Molecular Vision. 2006 12:467–77Google ScholarPubMed
de Gooyer, T.E., Stevenson, K.A., Humphries, P., Simpson, D.A., Gardiner, T.A., & Stitt, A.W. (2006). Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration. Investigative Ophthalmology Visual Science 47, 5561–5568.CrossRefGoogle Scholar
Dmitriev, A.V., Henderson, D., Lau, J.C., & Linsenmeier, R.A. (2014). Retinal acidosis at an early stage of diabetes in the rat. ARVO Meeting Abstracts 55, 1049.Google Scholar
Drapeau, P. & Nachshen, D.A. (1984). Manganese fluxes and manganese-dependent neurotransmitter release in presynaptic nerve endings isolated from rat brain. The Journal of Physiology 348, 493–510.CrossRefGoogle ScholarPubMed
Du, Y., Cramer, M., Lee, C.A., Tang, J., Muthusamy, A., Antonetti, D.A., Jin, H., Palczewski, K., & Kern, T.S. (2015). Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: Relationship to capillary degeneration and permeability. The FASEB Journal. 2015 29:2194–204.CrossRefGoogle ScholarPubMed
Du, Y., Veenstra, A., Palczewski, K., & Kern, T.S. (2013). Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina. Proceedings of the National Academy of Sciences 110, 16586–16591.CrossRefGoogle ScholarPubMed
Garcia-Ramirez, M., Hernandez, C., Villarroel, M., Canals, F., Alonso, M.A., Fortuny, R., Masmiquel, L., Navarro, A., Garcia-Arumi, J., & Simo, R. (2009). Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy. Diabetologia 52, 2633–2641.CrossRefGoogle ScholarPubMed
Gargioli, C., Turturici, G., Barreca, M.M., Spinello, W., Fuoco, C., Testa, S., Feo, S., Cannata, S.M., Cossu, G., Sconzo, G., & Geraci, F. (2018). Oxidative stress preconditioning of mouse perivascular myogenic progenitors selects a subpopulation of cells with a distinct survival advantage in vitro and in vivo. Cell Death & Disease 9, 1.CrossRefGoogle ScholarPubMed
Giordano, C.R., Roberts, R., Krentz, K.A., Bissig, D., Talreja, D., Kumar, A., Terlecky, S.R., & Berkowitz, B.A. (2015). Catalase therapy corrects oxidative stress-induced pathophysiology in incipient diabetic retinopathy. Investigative Ophthalmology Visual Science 56, 3095–3102.CrossRefGoogle ScholarPubMed
Gonzalez-Fernandez, F. (2003). Interphotoreceptor retinoid-binding protein – An old gene for new eyes. Vision Research 43, 3021–3036.CrossRefGoogle ScholarPubMed
Gonzalez-Fernandez, F., Fong, S.L., Liou, G.I., & Bridges, C.D. (1985). Interstitial retinol-binding protein (IRBP) in the RCS rat: Effect of dark-rearing. Investigative Ophthalmology & Visual Science 26, 1381–1385.Google ScholarPubMed
Govardovskii, V.I., Li, J.D., Dmitriev, A.V., & Steinberg, R.H. (1994). Mathematical model of TMA+ diffusion and prediction of light-dependent subretinal hydration in chick retina. Investigative Ophthalmology & Visual Science 35, 2712–2724.Google ScholarPubMed
Habermann, C.J., O'Brien, B.J., Wänssle, H., & Protti, D.A. (2003). All amacrine cells express L-type calcium channels at their output synapses. The Journal of Neuroscience 23, 6904–6913.CrossRefGoogle ScholarPubMed
Han, Y., Bearse, M.A. Jr., Schneck, M.E., Barez, S., Jacobsen, C.H., & Adams, A.J. (2004). Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy. Investigative Ophthalmology & Visual Science 45, 948–954.CrossRefGoogle ScholarPubMed
Harada, T., Harada, C., Kohsaka, S., Wada, E., Yoshida, K., Ohno, S., Mamada, H., Tanaka, K., Parada, L.F., & Wada, K. (2002). Microglia–Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. Journal of Neuroscience. 2002 22:9228–36CrossRefGoogle ScholarPubMed
Hasreiter, J., Goldnagl, L., Bohm, S., & Kubista, H. (2014). Cav1.2 and Cav1.3 L-type calcium channels operate in a similar voltage range but show different coupling to Ca(2+)-dependent conductances in hippocampal neurons. The American Journal of Physiolohy: Cell Physiology 306, C1200–C1213.CrossRefGoogle Scholar
Huang, B. & Karwoski, C.J. (1992). Light-evoked expansion of subretinal space volume in the retina of the frog. The Journal of Neuroscience 12, 4243–4252.CrossRefGoogle ScholarPubMed
Ishikawa, M., Sawada, Y., & Yoshitomi, T. (2015). Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells. Experimental Eye Research 133, 3–18.CrossRefGoogle ScholarPubMed
Ivanova, E., Roberts, R., Bissig, D., Pan, Z.H., & Berkowitz, B.A. (2010). Retinal channelrhodopsin-2-mediated activity in vivo evaluated with manganese-enhanced magnetic resonance imaging. Molecular Vision 16, 1059–1067.Google ScholarPubMed
Jeon, C.J., Strettoi, E., & Masland, R.H. (1998). The major cell populations of the mouse retina. The Journal of Neuroscience 18, 8936–8946.CrossRefGoogle ScholarPubMed
Johnson, J.E. Jr., Perkins, G.A., Giddabasappa, A., Chaney, S., Xiao, W., White, A.D., Brown, J.M., Waggoner, J., Ellisman, M.H., & Fox, D.A. (2007). Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses. Molecular Vision 13, 887–919.Google ScholarPubMed
Kanter, J.E., Kramer, F., Barnhart, S., Averill, M.M., Vivekanandan-Giri, A., Vickery, T., Li, L.O., Becker, L., Yuan, W., Chait, A., Braun, K.R., Potter-Perigo, S., Sanda, S., Wight, T.N., Pennathur, S., Serhan, C.N., Heinecke, J.W., Coleman, R.A., & Bornfeldt, K.E. (2012). Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through acyl-CoA synthetase 1. Proceedings of the National Academy of Sciences 109, E715–E724.CrossRefGoogle ScholarPubMed
Kern, T.S. (2017). Do photoreceptor cells cause the development of retinal vascular disease? Vision Research 139, 65–71.CrossRefGoogle ScholarPubMed
Kern, T.S. & Berkowitz, B.A. (2015). Photoreceptors in diabetic retinopathy. Journal of Diabetes Investigation 6, 371–380.CrossRefGoogle ScholarPubMed
Kern, T.S. & Engerman, R.L. (1996). Capillary lesions develop in retina rather than cerebral cortex in diabetes and experimental galactosemia. Archives of Ophthalmology 114, 306–310.CrossRefGoogle ScholarPubMed
Kezic, J.M., Chen, X., Rakoczy, E.P., & McMenamin, P.G. (2013). The effects of age and Cx3cr1 deficiency on retinal microglia in the Ins2(Akita) diabetic mouse. Investigative Ophthalmology & Visual Science 54, 854–863.CrossRefGoogle ScholarPubMed
Kim, Y.H., Kim, Y.S., Noh, H.S., Kang, S.S., Cheon, E.W., Park, S.K., Lee, B.J., Choi, W.S., & Cho, G.J. (2005). Changes in rhodopsin kinase and transducin in the rat retina in early-stage diabetes. Experimental Eye Research 80, 753–760.CrossRefGoogle ScholarPubMed
Ko, M.L., Liu, Y., Dryer, S.E., & Ko, G.Y.-P. (2007). The expression of L-type voltage-gated calcium channels in retinal photoreceptors is under circadian control. Journal of Neurochemistry 103, 784–792.CrossRefGoogle ScholarPubMed
Kooragayala, K., Gotoh, N., Cogliati, T., Nellissery, J., Kaden, T.R., French, S., Balaban, R., Li, W., Covian, R., & Swaroop, A. (2015). Quantification of oxygen consumption in retina ex vivo demonstrates limited reserve capacity of photoreceptor mitochondria. Investigative Ophthalmology & Visual Science 56, 8428–8436.CrossRefGoogle ScholarPubMed
Kowluru, A., Kowluru, R.A., & Yamazaki, A. (1992). Functional alterations of G-proteins in diabetic rat retina: A possible explanation for the early visual abnormalities in diabetes mellitus. Diabetologia 35, 624–631.CrossRefGoogle ScholarPubMed
Krizaj, D. (2012). Calcium stores in vertebrate photoreceptors. Advances in Experimental Medicine and Biology 740, 873–889.CrossRefGoogle ScholarPubMed
Kubota, R., Calkins, D.J., Henry, S.H., & Linsenmeier, R.A. (2019). Emixustat reduces metabolic demand of dark activity in the retina. Investigative Ophthalmology & Visual Science 60, 4924–4930.CrossRefGoogle ScholarPubMed
Lahdenranta, J., Pasqualini, R., Schlingemann, R.O., Hagedorn, M., Stallcup, W.B., Bucana, C.D., Sidman, R.L., & Arap, W. (2001). An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration. Proceedings of the National Academy of Sciences of United States of America 98, 10368–10373.CrossRefGoogle Scholar
Li, J.D., Gallemore, R.P., Dmitriev, A., & Steinberg, R.H. (1994a). Light-dependent hydration of the space surrounding photoreceptors in chick retina. Investigative Ophthalmology & Visual Science 35, 2700–2711.Google Scholar
Li, J.D., Govardovskii, V.I., & Steinberg, R.H. (1994b). Light-dependent hydration of the space surrounding photoreceptors in the cat retina. Visual Neuroscience 11, 743–752.CrossRefGoogle Scholar
Li, Y., Fariss, R.N., Qian, J.W., Cohen, E.D., & Qian, H. (2016). Light-induced thickening of photoreceptor outer segment layer detected by ultra-high resolution OCT imaging. Investigative Ophthalmology & Visual Science 57, 105–111.CrossRefGoogle ScholarPubMed
Liu, H., Tang, J., Du, Y., Lee, C.A., Golczak, M., Muthusamy, A., Antonetti, D.A., Veenstra, A.A., Amengual, J., von Lintig, J., Palczewski, K., & Kern, T.S. (2015). Retinylamine benefits early diabetic retinopathy in mice. Journal of Biological Chemistry. 2015 290:21568–79CrossRefGoogle ScholarPubMed
Liu, H., Tang, J., Du, Y., Saadane, A., Samuels, I., Veenstra, A., Kiser, J.Z., Palczewski, K., & Kern, T.S. (2019). Transducin1, phototransduction and the development of early diabetic retinopathy. Investigative Ophthalmology & Visual Science 60, 1538–1546.CrossRefGoogle ScholarPubMed
Lu, C.D., Lee, B., Schottenhamml, J., Maier, A., Pugh, E.N., & Fujimoto, J.G. (2017). Photoreceptor layer thickness changes during dark adaptation observed with ultrahigh-resolution optical coherence tomography. Investigative Ophthalmology & Visual Science 58, 4632–4643.CrossRefGoogle ScholarPubMed
Lyubarsky, A.L., Savchenko, A.B., Morocco, S.B., Daniele, L.L., Redmond, T.M., & Pugh, E.N. (2005). Mole quantity of RPE65 and its productivity in the generation of 11-cis-retinal from retinyl esters in the living mouse eye. Biochemistry 44, 9880–9888.CrossRefGoogle ScholarPubMed
MacGregor, L.C., & Matschinsky, F.M.. (1985). Treatment with aldose reductase inhibitor or with myo-inositol arrests deterioration of the electroretinogram of diabetic rats. Journal of Clinical Investigation 76 ,887–889.CrossRefGoogle ScholarPubMed
MacGregor, L.C. & Matschinsky, F.M. (1986a). Altered retinal metabolism in diabetes. II. Measurement of sodium-potassium ATPase and total sodium and potassium in individual retinal layers. The Journal of Biological Chemistry 261 ,4052–4058.Google Scholar
MacGregor, L.C. & Matschinsky, F.M. (1986b). Experimental diabetes mellitus impairs the function of the retinal pigmented epithelium. Metabolism 35, 28–34.CrossRefGoogle Scholar
Majdi, A., Mahmoudi, J., Sadigh-Eteghad, S., Golzari, S.E., Sabermarouf, B., & Reyhani-Rad, S. (2016). Permissive role of cytosolic pH acidification in neurodegeneration: A closer look at its causes and consequences. Journal of Neuroscience Reserach 94, 879–887.CrossRefGoogle Scholar
Malechka, V.V., Moiseyev, G., Takahashi, Y., Shin, Y., & Ma, J.X. (2017). Impaired rhodopsin generation in the rat model of diabetic retinopathy. The American Journal of Pathology 187, 2222–2231.CrossRefGoogle ScholarPubMed
Marella, M. & Chabry, J. (2004). Neurons and astrocytes respond to prion infection by inducing microglia recruitment. Journal of Neuroscience. 2004 24:620–7CrossRefGoogle ScholarPubMed
McAnany, J.J. & Park, J.C. (2018). Temporal frequency abnormalities in early-stage diabetic retinopathy assessed by electroretinography. Investigative Ophthalmology & Visual Science 59, 4871–4879.CrossRefGoogle ScholarPubMed
McAnany, J.J., Park, J.C., Chau, F.Y., Leiderman, Y.I., Lim, J.I., & Blair, N.P. (2019). Amplitude loss of the high-frequency flicker electroretinogram in early diabetic retinopathy. Retina 39, 2032–2039.CrossRefGoogle ScholarPubMed
Mei, X., Zhang, T., Ouyang, H., Lu, B., Wang, Z., & Ji, L. (2019). Scutellarin alleviates blood-retina-barrier oxidative stress injury initiated by activated microglia cells during the development of diabetic retinopathy. Biochemical Pharmacology 159, 82–95.CrossRefGoogle ScholarPubMed
Meimaridou, E., Kowalczyk, J., Guasti, L., Hughes, C.R., Wagner, F., Frommolt, P., Nurnberg, P., Mann, N.P., Banerjee, R., Saka, H.N., Chapple, J.P., King, P.J., Clark, A.J., & Metherell, L.A. (2012). Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nature Genetics 44, 740–742.CrossRefGoogle ScholarPubMed
Mellal, K., Omri, S., Mulumba, M., Tahiri, H., Fortin, C., Dorion, M.F., Pham, H., Garcia Ramos, Y., Zhang, J., Pundir, S., Joyal, J.S., Bouchard, J.F., Sennlaub, F., Febbraio, M., Hardy, P., Gravel, S.P., Marleau, S., Lubell, W.D., Chemtob, S., & Ong, H. (2019). Immunometabolic modulation of retinal inflammation by CD36 ligand. Science Reports 9, 12903.CrossRefGoogle ScholarPubMed
Mieziewska, K. (1996). The interphotoreceptor matrix, a space in sight. Microscopy Research and Technique 35, 463–471.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Morgans, C.W., Bayley, P.R., Oesch, N.W., Ren, G., Akileswaran, L., & Taylor, W.R. (2005). Photoreceptor calcium channels: insight from night blindness. Visual Neuroscience 22, 561–568.CrossRefGoogle ScholarPubMed
Morgans, C.W., Gaughwin, P., & Maleszka, R. (2001). Expression of the alpha1F calcium channel subunit by photoreceptors in the rat retina. Molecular Vision 7, 202–209.Google ScholarPubMed
Muir, E.R., Chandra, S.B., De La Garza, B.H., Velagapudi, C., Abboud, H.E., & Duong, T.Q. (2015). Layer-specific manganese-enhanced MRI of the diabetic rat retina in light and dark adaptation at 11.7 teslalight and dark adapted MRI of the diabetic retina. Investigative Ophthalmology & Visual Science 56, 4006–4012.CrossRefGoogle Scholar
Mulkey, D.K., Henderson, R.A. IIIrd, Ritucci, N.A., Putnam, R.W., & Dean, J.B. (2004). Oxidative stress decreases pHi and Na(+)/H(+) exchange and increases excitability of solitary complex neurons from rat brain slices. The American Journal of Physiology: Cell Physiology 286, C940–951.CrossRefGoogle ScholarPubMed
Muralidharan, P., Cserne Szappanos, H., Ingley, E., & Hool, L.C. (2017). The cardiac L-type calcium channel alpha subunit is a target for direct redox modification during oxidative stress-the role of cysteine residues in the alpha interacting domain. Clinical and Experimental Pharmacology and Physiology 44, 46–54.CrossRefGoogle ScholarPubMed
Naskar, R., Wissing, M., & Thanos, S. (2002). Detection of early neuron degeneration and accompanying microglial in the retina of a rat model of glaucoma. Investigative Ophthalmology & Visual Science. 2002 43:2962–8Google ScholarPubMed
Ng, T.F. & Streilein, J.W. (2001).Light-induced migration of retinal microglia into the subretinal space. Investigative Ophthalmology & Visual Science 2001 42:3301–10.Google ScholarPubMed
Omri, S., Behar-Cohen, F., de Kozak, Y., Sennlaub, F., Verissimo, L.M., Jonet, L., Savoldelli, M., Omri, B., & Crisanti, P. (2011). Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: Role of PKCζ in the Goto Kakizaki rat model. The American Journal of Pathology 179, 942–953.CrossRefGoogle ScholarPubMed
Ostroy, S.E. (1998). Altered rhodopsin regeneration in diabetic mice caused by acid conditions within the rod photoreceptors. Current Eye Research 17, 979–985.CrossRefGoogle ScholarPubMed
Ostroy, S.E., Frede, S.M., Wagner, E.F., Gaitatzes, C.G., & Janle, E.M. (1994). Decreased rhodopsin regeneration in diabetic mouse eyes. Investigative Ophthalmology & Visual Science 35, 3905–3909.Google ScholarPubMed
Phipps, J.A., Fletcher, E.L., & Vingrys, A.J. (2004). Paired-flash identification of rod and cone dysfunction in the diabetic rat. Investigative Ophthalmology & Visual Science 45, 4592–4600.CrossRefGoogle ScholarPubMed
Phipps, J.A., Yee, P., Fletcher, E.L., & Vingrys, A.J. (2006). Rod photoreceptor dysfunction in diabetes: activation, deactivation, and dark adaptation. Investigative Ophthalmology & Visual Science 47 ,3187-3194.CrossRefGoogle ScholarPubMed
Piggott, L.A., Hassell, K.A., Berkova, Z., Morris, A.P., Silberbach, M., & Rich, T.C. (2006). Natriuretic peptides and nitric oxide stimulate cGMP synthesis in different cellular compartments. The Journal of General Physiology 128, 3–14.CrossRefGoogle ScholarPubMed
Ramos de Carvalho, J.E., Verbraak, F.D., Aalders, M.C., van Noorden, C.J., & Schlingemann, R.O. (2014). Recent advances in ophthalmic molecular imaging. Survey of Ophthalmology 59, 393–413.CrossRefGoogle ScholarPubMed
Reichenbach, A., Wurm, A., Pannicke, T., Iandiev, I., Wiedemann, P., & Bringmann, A. (2007). Muller cells as players in retinal degeneration and edema. Graefe’s Archive for Clinical and Experimental Ophthalmology 245, 627–636.CrossRefGoogle ScholarPubMed
Rich, T.C., Xin, W., Leavesley, S.J., & Taylor, M.S. (2015). Channel-based reporters for cAMP detection. Methods in Molecular Biology 1294, 71–84.CrossRefGoogle ScholarPubMed
Rivera, J.C., Dabouz, R., Noueihed, B., Omri, S., Tahiri, H., & Chemtob, S. (2017). Ischemic retinopathies: Oxidative stress and inflammation. Oxidative Medicine and Cellular Longevity 2017, 3940241.CrossRefGoogle ScholarPubMed
Ronchi, J.A., Figueira, T.R., Ravagnani, F.G., Oliveira, H.C., Vercesi, A.E., & Castilho, R.F. (2013). A spontaneous mutation in the nicotinamide nucleotide transhydrogenase gene of C57BL/6J mice results in mitochondrial redox abnormalities. Free Radical Biology and Medicine 63, 446–456.CrossRefGoogle ScholarPubMed
Roque, R.S., Imperial, C.J., & Caldwell, R.B. (1996). Microglial cells invade the outer retina as photoreceptors degenerate in Royal College of Surgeons rats. Investigative Ophthalmology & Visual Science. 1996 37:196–203Google ScholarPubMed
Roy, S., Kern, T.S., Song, B., & Stuebe, C. (2017). Mechanistic insights into pathological changes in the diabetic retina: Implications for targeting diabetic retinopathy. The American Journal of Pathology 187, 9–19.CrossRefGoogle ScholarPubMed
Saliba, A., Du, Y., Liu, H., Patel, S., Roberts, R., Berkowitz, B.A., & Kern, T.S. (2015). Photobiomodulation mitigates diabetes-induced retinopathy by direct and indirect mechanisms: Evidence from intervention studies in pigmented mice. PLoS ONE 10, e0139003.CrossRefGoogle ScholarPubMed
Samuels, I.S., Bell, B.A., Pereira, A., Saxon, J., & Peachey, N.S. (2015). Early retinal pigment epithelium dysfunction is concomitant with hyperglycemia in mouse models of type 1 and type 2 diabetes. Journal of Neurophysiology 113, 1085–1099.CrossRefGoogle ScholarPubMed
Santos, A.M., Martin-Oliva, D., Ferrer-Martin, R.M., Tassi, M., Calvente, R., Sierra, A., Carrasco, M.C., Marin-Teva, J.L., Navascues, J., & Cuadros, M.A. (2010). Microglial response to light-induced photoreceptor degeneration in the mouse retina. The Journal of Comparative Neurology. 2010 518:477–92CrossRefGoogle ScholarPubMed
Semenova, E.M. & Converse, C.A. (2003). Comparison between oleic acid and docosahexaenoic acid binding to interphotoreceptor retinoid-binding protein. Vision Research 43, 3063–3067.CrossRefGoogle ScholarPubMed
Sharma, A., Liaw, K., Sharma, R., Zhang, Z., Kannan, S., & Kannan, R.M. (2018). Targeting mitochondrial dysfunction and oxidative stress in activated microglia using dendrimer-based therapeutics. Theranostics 8, 5529–5547.CrossRefGoogle ScholarPubMed
Shi, L., Chang, J.Y.-A., Yu, F., Ko, M.L., & Ko, G.Y.-P. (2017). The contribution of L-type Cav1.3 channels to retinal light responses Frontiers in Molecular Neuroscience 2017 10:394.CrossRefGoogle ScholarPubMed
Simms, B.A. & Zamponi, G.W. (2014). Neuronal voltage-gated calcium channels: Structure, function, and dysfunction. Neuron 82, 24–45.CrossRefGoogle ScholarPubMed
Sokol, S., Moskowitz, A., Skarf, B., Evans, R., Molitch, M., & Senior, B. (1985). COntrast sensitivity in diabetics with and without background retinopathy. Archives of Ophthalmology 103, 51–54.CrossRefGoogle ScholarPubMed
Sudarshana, D.M., Nair, G., Dwyer, J.T., Dewey, B., Steele, S.U., Suto, D.J., Wu, T., Berkowitz, B.A., Koretsky, A.P., Cortese, I.C.M., & Reich, D.S. (2019). Manganese-enhanced MRI of the brain in healthy volunteers. American Journal of Neuroradiology 40, 1309–1316.CrossRefGoogle ScholarPubMed
Sun, Z., Zhang, M., Liu, W., Tian, J., & Xu, G. (2016). Photoreceptor IRBP prevents light induced injury. Frontiers in Bioscience 21, 958–972.Google ScholarPubMed
Sung, C.-H. & Chuang, J.-Z. (2010). The cell biology of vision. The Journal of cell biology 190, 953–963.CrossRefGoogle Scholar
Tarchick, M.J., Cutler, A.H., Trobenter, T.D., Kozlowski, M.R., Makowski, E.R., Holoman, N., Shao, J., Shen, B., Anand-Apte, B., & Samuels, I.S. (2019). Endogenous insulin signaling in the RPE contributes to the maintenance of rod photoreceptor function in diabetes. Experimental Eye Research 180, 63–74.CrossRefGoogle ScholarPubMed
Tofts, P.S., Porchia, A., Jin, Y., Roberts, R., & Berkowitz, B.A. (2010). Toward clinical application of manganese-enhanced MRI of retinal function. Brain Research Bulletin 81, 333–338.CrossRefGoogle ScholarPubMed
Trick, G.L., Burde, R.M., Gordon, M.O., Santiago, J.V., & Kilo, C. (1988). The relationship between hue discrimination and contrast sensitivity deficits in patients with diabetes mellitus. Ophthalmology 95, 693–698.CrossRefGoogle ScholarPubMed
Tsai, K.L., Wang, S.M., Chen, C.C., Fong, T.H., & Wu, M.L. (1997). Mechanism of oxidative stress-induced intracellular acidosis in rat cerebellar astrocytes and C6 glioma cells. Journal of Physiology 502, 161–174.CrossRefGoogle ScholarPubMed
Uehara, F., Matthes, M.T., Yasumura, D., & LaVail, M.M. (1990). Light-evoked changes in the interphotoreceptor matrix. Science 248, 1633–1636.CrossRefGoogle ScholarPubMed
Uehara, F., Yasumura, D., & LaVail, M.M. (1991). Development of light-evoked changes of the interphotoreceptor matrix in normal and RCS rats with inherited retinal dystrophy. Experimental Eye Research 53, 55–60.CrossRefGoogle ScholarPubMed
Wolfensberger, T.J., Dmitriev, A.V., & Govardovskii, V.I. (1999). Inhibition of membrane-bound carbonic anhydrase decreases subretinal pH and volume. Documenta Ophthalmologica 97, 261–271.CrossRefGoogle ScholarPubMed
Wong, V.H.Y., Vingrys, A.J., & Bui, B.V. (2011). Glial and neuronal dysfunction in streptozotocin-induced diabetic rats. Journal of Ocular Biology, Disease, and Informatics 4, 42–50.CrossRefGoogle ScholarPubMed
Wu, J., Marmorstein, A.D., Striessnig, J., & Peachey, N.S. (2007). Voltage-dependent calcium channel CaV1.3 subunits regulate the light peak of the electroretinogram. Journal of Neurophysiology 97, 3731–3735.CrossRefGoogle ScholarPubMed
Xiao, H., Chen, X., & Steele, E.C. Jr. (2007). Abundant L-type calcium channel Ca(v)1.3 (alpha1D) subunit mRNA is detected in rod photoreceptors of the mouse retina via in situ hybridization. Molecular Vision 13, 764–771.Google ScholarPubMed
Xu, H., Chen, M., Manivannan, A., Lois, N., & Forrester, J.V. (2008). Age–dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice. Aging Cell 7.CrossRefGoogle ScholarPubMed
Xu, H.P., Zhao, J.W., & Yang, X.L. (2002). Expression of voltage-dependent calcium channel subunits in the rat retina. Neuroscience Letters 329, 297–300.CrossRefGoogle ScholarPubMed
Xu, W. & Lipscombe, D. (2001). Neuronal CaV1.3+¦1 L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. The Journal of Neuroscience 21, 5944–5951.CrossRefGoogle ScholarPubMed
Yamamoto, F. & Steinberg, R.H. (1992). Effects of intravenous acetazolamide on retinal pH in the cat. Experimental Eye Research 54, 711–718.CrossRefGoogle ScholarPubMed
Yang, L., Xu, J., Minobe, E., Yu, L., Feng, R., Kameyama, A., Yazawa, K., & Kameyama, M. (2013). Mechanisms underlying the modulation of L-type Ca2+ channel by hydrogen peroxide in guinea pig ventricular myocytes. Journal of Physiological Science 63, 419–426.CrossRefGoogle ScholarPubMed
Yauger, Y.J., Bermudez, S., Moritz, K.E., Glaser, E., Stoica, B., & Byrnes, K.R. (2019). Iron accentuated reactive oxygen species release by NADPH oxidase in activated microglia contributes to oxidative stress in vitro. Journal of Neuroinflammation 16, 41.CrossRefGoogle ScholarPubMed
Yokomizo, H., Maeda, Y., Park, K., Clermont, A.C., Hernandez, S.L., Fickweiler, W., Li, Q., Wang, C.H., Paniagua, S.M., Simao, F., Ishikado, A., Sun, B., Wu, I.H., Katagiri, S., Pober, D.M., Tinsley, L.J., Avery, R.L., Feener, E.P., Kern, T.S., Keenan, H.A., Aiello, L.P., Sun, J.K., & King, G.L. (2019). Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy. Science Translational Medicine 2019 Jul 3;11(499):eaau6627.doi: 10.1126/scitranslmed.aau6627.CrossRefGoogle ScholarPubMed
Zeng, H.Y., Green, W.R., & Tso, M.O. (2008). Microglial activation in human diabetic retinopathy. Archives of Ophthalmology 126, 227–232.CrossRefGoogle ScholarPubMed
Zeng, X.-X., Ng, Y.-K., & Ling, E.-A. (2000). Neuronal and microglial response in the retina of streptozotocin-induced diabetic rats. Visual Neuroscience 17, 463–471.CrossRefGoogle ScholarPubMed
Zhang, C., Shen, J., Lam, T.T., Zeng, H., Chiang, S.K., Yang, F., & Tso, M. (2005). Activation of microglia and chemokines in light-induced retinal degeneration. Moleular Vision 2005 11:887–95.Google ScholarPubMed
Zhang, P., Zawadzki, R.J., Goswami, M., Nguyen, P.T., Yarov-Yarovoy, V., Burns, M.E., & Pugh, E.N. (2017). In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors. Proceedings of the National Academy of Sciences of the United States of America 114, E2937–E2946.CrossRefGoogle ScholarPubMed
Zhang, S., Xu, J., Feng, Y., Zhang, J., Cui, L., Zhang, H., & Bai, Y. (2018). Extracellular acidosis suppresses calcification of vascular smooth muscle cells by inhibiting calcium influx via L-type calcium channels. Clinical and Experimental Hypertension 40, 370–377.CrossRefGoogle ScholarPubMed
Zhao, L., Feng, Z., Zou, X., Cao, K., Xu, J., & Liu, J. (2014). Aging leads to elevation of O-GlcNAcylation and disruption of mitochondrial homeostasis in retina. Oxidative Medicine and Cellular Longevity 2014, 425705.CrossRefGoogle ScholarPubMed