{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:31:53Z","timestamp":1790793113246,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R21 EY033046 01"],"award-info":[{"award-number":["R21 EY033046 01"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The retina is one of the most metabolically active organs in the body. Although it is an extension of the brain, the metabolic needs of the retina and metabolic exchanges between the different cell types in the retina are not the same as that of the brain. Retinal photoreceptors convert most of the glucose into lactate via aerobic glycolysis which takes place in their cytosol, yet there are immense numbers of mitochondria in photoreceptors. The present article is a focused review of the metabolic dysregulation seen in retinopathies with underlying vascular abnormalities with aberrant mitochondrial metabolism and Hypoxia-inducible factor (HIF) dependent pathogenesis. Special emphasis has been paid to metabolic exchanges between different cell types in retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Metabolic similarities between these proliferative retinopathies have been discussed.<\/jats:p>","DOI":"10.3390\/diagnostics12040903","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T11:26:07Z","timestamp":1649157967000},"page":"903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Metabolism and Vascular Retinopathies: Current Perspectives and Future Directions"],"prefix":"10.3390","volume":"12","author":[{"given":"Charandeep","family":"Singh","sequence":"first","affiliation":[{"name":"Liver Center, Division of Gastroenterology, Mass General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0034-5288(18)31228-1","article-title":"Retinal vascular patterns in domestic animals","volume":"47","author":"Simoens","year":"1989","journal-title":"Res. Vet. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S253","DOI":"10.1016\/S0039-6257(02)00387-9","article-title":"Diabetic Retinopathy: More Than Meets the Eye","volume":"47","author":"Gardner","year":"2002","journal-title":"Surv. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10456-007-9067-z","article-title":"Vascular permeability in ocular disease and the role of tight junctions","volume":"10","author":"Erickson","year":"2007","journal-title":"Angiogenesis"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nrn3723","article-title":"M\u00fcller glial cell reprogramming and retina regeneration","volume":"15","author":"Goldman","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1615\/CritRevImmunol.2013006618","article-title":"Muller glia in retinal innate immunity: A perspective on their roles in endophthalmitis","volume":"33","author":"Kumar","year":"2013","journal-title":"Crit. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000328979","article-title":"M\u00fcller Glial Cells in Retinal Disease","volume":"227","author":"Bringmann","year":"2012","journal-title":"Ophthalmologica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","article-title":"M\u00fcller cells in the healthy and diseased retina","volume":"25","author":"Bringmann","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.2741\/Bringman","article-title":"Role of Muller cells in retinal degenerations","volume":"6","author":"Bringmann","year":"2001","journal-title":"Front. Biosci. Landmark"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1023\/A:1006934724566","article-title":"Distribution of mitochondria within M\u00fcller cells\u2014I. Correlation with retinal vascularization in different mammalian species","volume":"27","author":"Germer","year":"1998","journal-title":"J. Neurocytol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1146\/annurev-vision-100419-115156","article-title":"Retina Metabolism and Metabolism in the Pigmented Epithelium: A Busy Intersection","volume":"7","author":"Hurley","year":"2021","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s00726-021-02981-1","article-title":"Proline metabolism and transport in retinal health and disease","volume":"53","author":"Du","year":"2021","journal-title":"Amino Acids"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"C121","DOI":"10.1152\/ajpcell.00410.2018","article-title":"Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: Impact on photoreceptors and M\u00fcller glial cells","volume":"316","author":"Swarup","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10278","DOI":"10.1074\/jbc.RA119.007983","article-title":"Proline mediates metabolic communication between retinal pigment epithelial cells and the retina","volume":"294","author":"Yam","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e25946","DOI":"10.7554\/eLife.25946","article-title":"Glycolytic reliance promotes anabolism in photoreceptors","volume":"6","author":"Chinchore","year":"2017","journal-title":"Elife"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1085\/jgp.77.6.667","article-title":"Glycolytic and oxidative metabolism in relation to retinal function","volume":"77","author":"Winkler","year":"1981","journal-title":"J. Gen. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/jnr.23583","article-title":"Glucose, lactate, and shuttling of metabolites in vertebrate retinas","volume":"93","author":"Hurley","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1471-4159.1960.tb13363.x","article-title":"Glucose catabolism of rabbit retina before and after development of visual function","volume":"5","author":"Cohen","year":"1960","journal-title":"J. Neurochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1016\/S0021-9258(19)61742-4","article-title":"Quantitative Histochemistry of Retina: II. Enzymes of Glucose Metabolism","volume":"236","author":"Lowry","year":"1961","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0021-9258(18)65313-X","article-title":"The quantitative histochemistry of the retina","volume":"220","author":"Lowry","year":"1956","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nm.4059","article-title":"Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1","volume":"22","author":"Joyal","year":"2016","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00418-010-0752-4","article-title":"Immunohistochemical localization of mitochondrial fatty acid \u03b2-oxidation enzymes in M\u00fcller cells of the retina","volume":"134","author":"Atsuzawa","year":"2010","journal-title":"Histochem. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Heckel, E., Cagnone, G., Agnihotri, T., Cakir, B., Das, A., Kim, J.S., Kim, N., Lavoie, G., Situ, A., and Pundir, S. (2022). Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation. JCI Insight.","DOI":"10.1172\/jci.insight.154174"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9361","DOI":"10.1128\/MCB.23.24.9361-9374.2003","article-title":"Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation","volume":"23","author":"Hu","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nm0603-677","article-title":"Regulation of angiogenesis by hypoxia: Role of the HIF system","volume":"9","author":"Pugh","year":"2003","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.15252\/embj.201696150","article-title":"Endothelial cell metabolism in health and disease: Impact of hypoxia","volume":"36","author":"Wong","year":"2017","journal-title":"EMBO J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nature04478","article-title":"Angiogenesis in life, disease and medicine","volume":"438","author":"Carmeliet","year":"2005","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e129398","DOI":"10.1172\/jci.insight.129398","article-title":"Serine and 1-carbon metabolism are required for HIF-mediated protection against retinopathy of prematurity","volume":"4","author":"Singh","year":"2019","journal-title":"JCI Insight"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jaapos.2012.12.155","article-title":"Effects of oxygen on the development and severity of retinopathy of prematurity","volume":"17","author":"Hartnett","year":"2013","journal-title":"J. Aapos"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S1084-2756(03)00119-2","article-title":"Pathogenesis of retinopathy of prematurity","volume":"8","author":"Smith","year":"2003","journal-title":"Semin. Neonatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1167\/iovs.08-2584","article-title":"Through the eyes of a child: Understanding retinopathy through ROP the Friedenwald lecture","volume":"49","author":"Smith","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1056\/NEJMra1208129","article-title":"Mechanisms and Management of Retinopathy of Prematurity","volume":"367","author":"Hartnett","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.2741\/1056","article-title":"Animal models of oxygen-induced retinopathy","volume":"8","author":"Madan","year":"2003","journal-title":"Front. Biosci."},{"key":"ref_34","first-page":"101","article-title":"Oxygen-induced retinopathy in the mouse","volume":"35","author":"Smith","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.15252\/embj.201796436","article-title":"Glutamine fuels proliferation but not migration of endothelial cells","volume":"36","author":"Kim","year":"2017","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.cmet.2013.08.001","article-title":"Role of endothelial cell metabolism in vessel sprouting","volume":"18","author":"Georgiadou","year":"2013","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0166-2236(96)10040-0","article-title":"The M\u00fcller cell: A functional element of the retina","volume":"19","author":"Newman","year":"1996","journal-title":"Trends Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.preteyeres.2017.11.002","article-title":"Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism","volume":"64","author":"Joyal","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1128\/MCB.00161-15","article-title":"Hypoxia Signaling Cascade for Erythropoietin Production in Hepatocytes","volume":"35","author":"Tojo","year":"2015","journal-title":"Mol. Cell. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/01.LAB.0000050761.67879.E4","article-title":"Hypoxic preconditioning augments efficacy of human endothelial progenitor cells for therapeutic neovascularization","volume":"83","author":"Akita","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0304-3940(94)90455-3","article-title":"Neuroprotection from ischemic brain injury by hypoxic preconditioning in the neonatal rat","volume":"168","author":"Gidday","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nm723","article-title":"HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration","volume":"8","author":"Grimm","year":"2002","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1161\/CIRCULATIONAHA.107.758516","article-title":"Hypoxia-Inducible Factor-1 Is Central to Cardioprotection","volume":"118","author":"Eckle","year":"2008","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19898","DOI":"10.1073\/pnas.0805817105","article-title":"Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy","volume":"105","author":"Sears","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E2516","DOI":"10.1073\/pnas.1523005113","article-title":"Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity","volume":"113","author":"Hoppe","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1167\/iovs.18-24120","article-title":"3-Hydroxypyruvate Destabilizes Hypoxia Inducible Factor and Induces Angiostasis","volume":"59","author":"Singh","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11306-015-0877-5","article-title":"Global metabolomics reveals metabolic dysregulation in ischemic retinopathy","volume":"12","author":"Paris","year":"2015","journal-title":"Metabolomics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s00125-020-05309-y","article-title":"Vitreous metabolomics profiling of proliferative diabetic retinopathy","volume":"64","author":"Tomita","year":"2021","journal-title":"Diabetologia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1167\/iovs.62.10.9","article-title":"Metabolomics Analyses of Mouse Retinas in Oxygen-Induced Retinopathy","volume":"62","author":"Zhou","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.7150\/ijms.63603","article-title":"Plasma levels of amino acids and derivatives in retinopathy of prematurity","volume":"18","author":"Zhou","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e1075","DOI":"10.1038\/cddis.2014.23","article-title":"Arginase 2 deficiency reduces hyperoxia-mediated retinal neurodegeneration through the regulation of polyamine metabolism","volume":"5","author":"Narayanan","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Singh, C., Benos, A., Grenell, A., Rao, S., Anand-Apte, B., and Sears, J.E. (2021). Hyperoxia Inhibits Proliferation of Retinal Endothelial Cells in a Myc-Dependent Manner. Life, 11.","DOI":"10.3390\/life11070614"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.biocel.2013.02.021","article-title":"Role of polyamines at the G1\/S boundary and G2\/M phase of the cell cycle","volume":"45","author":"Yamashita","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/s41467-020-15066-6","article-title":"Hyperoxia induces glutamine-fuelled anaplerosis in retinal M\u00fcller cells","volume":"11","author":"Singh","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1001\/jamapediatrics.2020.5653","article-title":"Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial","volume":"175","author":"Nilsson","year":"2021","journal-title":"JAMA Pediatr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1001\/jamaophthalmol.2017.6658","article-title":"Association of Retinopathy of Prematurity with Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial","volume":"136","author":"Najm","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e10473","DOI":"10.15252\/emmm.201910473","article-title":"Dyslipidemia in retinal metabolic disorders","volume":"11","author":"Fu","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Tomita, Y., Usui-Ouchi, A., Nilsson, A.K., Yang, J., Ko, M., Hellstr\u00f6m, A., and Fu, Z. (2021). Metabolism in Retinopathy of Prematurity. Life, 11.","DOI":"10.3390\/life11111119"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nm1591","article-title":"Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis","volume":"13","author":"Connor","year":"2007","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"879","DOI":"10.3945\/ajcn.114.099291","article-title":"Dietary \u03c9-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin","volume":"101","author":"Fu","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajo.2012.10.018","article-title":"Age-related macular degeneration revisited\u2014Piecing the puzzle: The LXIX Edward Jackson memorial lecture","volume":"155","author":"Miller","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14682","DOI":"10.1073\/pnas.222551899","article-title":"Drusen proteome analysis: An approach to the etiology of age-related macular degeneration","volume":"99","author":"Crabb","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17429","DOI":"10.1038\/s41598-019-53433-6","article-title":"Sorsby Fundus Dystrophy Mutation in Tissue Inhibitor of Metalloproteinase 3 (TIMP3) promotes Choroidal Neovascularization via a Fibroblast Growth Factor-dependent Mechanism","volume":"9","author":"Qi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_64","first-page":"73","article-title":"Juvenile neuronal ceroid lipofuscinosis (Batten disease): Current insights","volume":"6","author":"Ostergaard","year":"2016","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ajmg.1320420428","article-title":"Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten disease)","volume":"42","author":"Palmer","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"12895","DOI":"10.1074\/jbc.M117.788422","article-title":"Human retinal pigment epithelial cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side","volume":"292","author":"Chao","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"14710","DOI":"10.1073\/pnas.1604572113","article-title":"Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium","volume":"113","author":"Du","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"La\u00edns, I., Chung, W., Kelly, R.S., Gil, J., Marques, M., Barreto, P., Murta, J.N., Kim, I.K., Vavvas, D.G., and Miller, J.B. (2019). Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts. Metabolites, 9.","DOI":"10.3390\/metabo9070127"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mitchell, S.L., Ma, C., Scott, W.K., Agarwal, A., Pericak-Vance, M.A., Haines, J.L., Jones, D.P., Uppal, K., and Brantley, M.A. (2021). Plasma Metabolomics of Intermediate and Neovascular Age-Related Macular Degeneration Patients. Cells, 10.","DOI":"10.3390\/cells10113141"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.ophtha.2020.06.020","article-title":"Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration: The EYE-RISK Consortium","volume":"127","author":"Acar","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1136\/bjo.2005.077370","article-title":"Mouse models may provide new insight into the relation between cholesterol and age related macular degeneration","volume":"89","author":"Duncan","year":"2005","journal-title":"Br. J. Ophthalmol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1523\/JNEUROSCI.2010-20.2021","article-title":"Reduction of Glut1 in the Neural Retina But Not the RPE Alleviates Polyol Accumulation and Normalizes Early Characteristics of Diabetic Retinopathy","volume":"41","author":"Holoman","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/BF03401589","article-title":"Nerve growth factor prevents both neuroretinal programmed cell death and capillary pathology in experimental diabetes","volume":"1","author":"Hammes","year":"1995","journal-title":"Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yun, J.H., Kim, J.M., Jeon, H.J., Oh, T., Choi, H.J., and Kim, B.J. (2020). Metabolomics profiles associated with diabetic retinopathy in type 2 diabetes patients. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241365"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12986-019-0358-3","article-title":"Plasma metabolomic profiling of proliferative diabetic retinopathy","volume":"16","author":"Zhu","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1167\/iovs.19-27321","article-title":"Arginine and Carnitine Metabolites Are Altered in Diabetic Retinopathy","volume":"60","author":"Sumarriva","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ajo.2021.09.021","article-title":"Plasma Arginine and Citrulline are Elevated in Diabetic Retinopathy","volume":"235","author":"Peters","year":"2021","journal-title":"Am. J. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"757088","DOI":"10.3389\/fendo.2021.757088","article-title":"Plasma Metabolomics Reveals Metabolic Profiling for Diabetic Retinopathy and Disease Progression","volume":"12","author":"Sun","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11306-019-1548-8","article-title":"NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db\/db mice","volume":"15","author":"Oregioni","year":"2019","journal-title":"Metabolomics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s40200-020-00570-9","article-title":"Mechanistic dissection of diabetic retinopathy using the protein-metabolite interactome","volume":"19","author":"Patrick","year":"2020","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9802","DOI":"10.1038\/s41598-020-66092-9","article-title":"Cell Atlas of The Human Fovea and Peripheral Retina","volume":"10","author":"Yan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"14520","DOI":"10.1038\/s41598-018-32871-8","article-title":"Three-Dimensional Retinal Organoids Facilitate the Investigation of Retinal Ganglion Cell Development, Organization and Neurite Outgrowth from Human Pluripotent Stem Cells","volume":"8","author":"Fligor","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10824","DOI":"10.1073\/pnas.1901572116","article-title":"Generation, transcriptome profiling, and functional validation of cone-rich human retinal organoids","volume":"116","author":"Kim","year":"2019","journal-title":"Proc. Natl. Acad. Sci. 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