[1]

Chong DD, Das N, Singh RP. 2024. Diabetic retinopathy: screening, prevention, and treatment. Cleveland Clinic Journal of Medicine 91:503−10

doi: 10.3949/ccjm.91a.24028
[2]

Cheung N, Mitchell P, Wong TY. 2010. Diabetic retinopathy. The Lancet 376:124−36

doi: 10.1016/S0140-6736(09)62124-3
[3]

Rolev KD, Shu XS, Ying Y. 2021. Targeted pharmacotherapy against neurodegeneration and neuroinflammation in early diabetic retinopathy. Neuropharmacology 187:108498

doi: 10.1016/j.neuropharm.2021.108498
[4]

Simó R, Simó-Servat O, Bogdanov P, Hernández C. 2022. Diabetic retinopathy: role of neurodegeneration and therapeutic perspectives. Asia-Pacific Journal of Ophthalmology 11:160−67

doi: 10.1097/APO.0000000000000510
[5]

Fragiotta S, Pinazo-Durán MD, Scuderi G. 2022. Understanding neurodegeneration from a clinical and therapeutic perspective in early diabetic retinopathy. Nutrients 14:792

doi: 10.3390/nu14040792
[6]

Spencer BG, Estevez JJ, Liu E, Craig JE, Finnie JW. 2020. Pericytes, inflammation, and diabetic retinopathy. Inflammopharmacology 28:697−709

doi: 10.1007/s10787-019-00647-9
[7]

Tan TE, Wong TY. 2023. Diabetic retinopathy: looking forward to 2030. Frontiers in Endocrinology 13:1077669

doi: 10.3389/fendo.2022.1077669
[8]

Wang W, Lo ACY. 2018. Diabetic retinopathy: pathophysiology and treatments. International Journal of Molecular Sciences 19:1816

doi: 10.3390/ijms19061816
[9]

Whitehead M, Wickremasinghe S, Osborne A, Van Wijngaarden P, Martin KR. 2018. Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies. Expert Opinion on Biological Therapy 18:1257−70

doi: 10.1080/14712598.2018.1545836
[10]

Amoaku WM, Ghanchi F, Bailey C, Banerjee S, Banerjee S, et al. 2020. Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group. Eye 34:1−51

doi: 10.1038/s41433-020-0961-6
[11]

Wong TY, Cheung CMG, Larsen M, Sharma S, Simó R. 2016. Diabetic retinopathy. Nature Reviews Disease Primers 2:16012

doi: 10.1038/nrdp.2016.12
[12]

Seo H, Park SJ, Song M. 2025. Diabetic retinopathy (DR): mechanisms, current therapies, and emerging strategies. Cells 14:376

doi: 10.3390/cells14050376
[13]

Cohen SR, Gardner TW. 2016. Diabetic retinopathy and diabetic macular edema. Developments in Ophthalmology 55:137−46

doi: 10.1159/000438970
[14]

Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, et al. 2012. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35:556−64

doi: 10.2337/dc11-1909
[15]

Tey KY, Teo K, Tan ACS, Devarajan K, Tan B, et al. 2019. Optical coherence tomography angiography in diabetic retinopathy: a review of current applications. Eye and Vision 6:37

doi: 10.1186/s40662-019-0160-3
[16]

Song P, Yu J, Chan KY, Theodoratou E, Rudan I. 2018. Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis. Journal of Global Health 8:010803

doi: 10.7189/jogh.08.010803
[17]

Bethel MA, Diaz R, Castellana N, Bhattacharya I, Gerstein HC, et al. 2021. HbA1c change and diabetic retinopathy during GLP-1 receptor agonist cardiovascular outcome trials: a meta-analysis and meta-regression. Diabetes Care 44:290−96

doi: 10.2337/dc20-1815
[18]

Chandrasekaran PR, Madanagopalan VG, Narayanan R. 2021. Diabetic retinopathy in pregnancy - a review. Indian Journal of Ophthalmology 69:3015−25

doi: 10.4103/ijo.ijo_1377_21
[19]

Wu MY, Yiang GT, Lai TT, Li CJ. 2018. The oxidative stress and mitochondrial dysfunction during the pathogenesis of diabetic retinopathy. Oxidative Medicine and Cellular Longevity 2018:3420187

doi: 10.1155/2018/3420187
[20]

Jadeja RN, Martin PM. 2021. Oxidative stress and inflammation in retinal degeneration. Antioxidants 10:790

doi: 10.3390/antiox10050790
[21]

Kang Q, Yang C. 2020. Oxidative stress and diabetic retinopathy: molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biology 37:101799

doi: 10.1016/j.redox.2020.101799
[22]

Chen C, Ding P, Yan W, Wang Z, Lan Y, et al. 2023. Pharmacological roles of lncRNAs in diabetic retinopathy with a focus on oxidative stress and inflammation. Biochemical Pharmacology 214:115643

doi: 10.1016/j.bcp.2023.115643
[23]

Simó R, Hernández C. 2014. Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends in Endocrinology & Metabolism 25:23−33

doi: 10.1016/j.tem.2013.09.005
[24]

Moran EP, Wang Z, Chen J, Sapieha P, Smith LEH, et al. 2016. Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications. American Journal of Physiology Heart and Circulatory Physiology 311:H738−H749

doi: 10.1152/ajpheart.00005.2016
[25]

Park DY, Lee J, Kim J, Kim K, Hong S, et al. 2017. Plastic roles of pericytes in the blood-retinal barrier. Nature Communications 8:15296

doi: 10.1038/ncomms15296
[26]

Guo C, Deshpande M, Niu Y, Kachwala I, Flores-Bellver M, et al. 2023. HIF-1α accumulation in response to transient hypoglycemia may worsen diabetic eye disease. Cell Reports 42:111976

doi: 10.1016/j.celrep.2022.111976
[27]

Li HY, Yuan Y, Fu YH, Wang Y, Gao XY. 2020. Hypoxia-inducible factor-1α: a promising therapeutic target for vasculopathy in diabetic retinopathy. Pharmacological Research 159:104924

doi: 10.1016/j.phrs.2020.104924
[28]

Ferrão JSP, Bonfim Neto AP, da Fonseca VU, de C Sousa LMM, de C Papa P. 2019. Vascular endothelial growth factor C treatment for mouse hind limb lymphatic revascularization. Veterinary Medicine and Science 5:249−59

doi: 10.1002/vms3.151
[29]

Tirpe AA, Gulei D, Ciortea SM, Crivii C, Berindan-Neagoe I. 2019. Hypoxia: overview on hypoxia-mediated mechanisms with a focus on the role of HIF genes. International Journal of Molecular Sciences 20:6140

doi: 10.3390/ijms20246140
[30]

Titchenell PM, Lin CM, Keil JM, Sundstrom JM, Smith CD, et al. 2012. Novel atypical PKC inhibitors prevent vascular endothelial growth factor-induced blood-retinal barrier dysfunction. Biochemical Journal 446:455−67

doi: 10.1042/BJ20111961
[31]

Klaassen I, Van Noorden CJF, Schlingemann RO. 2013. Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Progress in Retinal and Eye Research 34:19−48

doi: 10.1016/j.preteyeres.2013.02.001
[32]

Tan GS, Cheung N, Simó R, Cheung GCM, Wong TY. 2017. Diabetic macular oedema. The Lancet Diabetes & Endocrinology 5:143−55

doi: 10.1016/S2213-8587(16)30052-3
[33]

Kong X, Bu J, Chen J, Ni B, Fu B, et al. 2021. PIGF and Flt-1 on the surface of macrophages induces the production of TGF-β1 by polarized tumor-associated macrophages to promote lung cancer angiogenesis. European Journal of Pharmacology 912:174550

doi: 10.1016/j.ejphar.2021.174550
[34]

Semeraro F, Cancarini A, dell'Omo R, Rezzola S, Romano MR, et al. 2015. Diabetic retinopathy: vascular and inflammatory disease. Journal of Diabetes Research 2015:582060

doi: 10.1155/2015/582060
[35]

Storti F, Pulley J, Kuner P, Abt M, Luhmann UFO. 2021. Circulating biomarkers of inflammation and endothelial activation in diabetic retinopathy. Translational Vision Science & Technology 10:8

doi: 10.1167/tvst.10.12.8
[36]

Gao X, Li Y, Wang H, Li C, Ding J. 2017. Inhibition of HIF-1α decreases expression of pro-inflammatory IL-6 and TNF-α in diabetic retinopathy. Acta Ophthalmologica 95:e746−e750

doi: 10.1111/aos.13096
[37]

Du Y, Veenstra A, Palczewski K, Kern TS. 2013. Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina. Proceedings of the National Academy of Sciences of the United States of America 110:16586−91

doi: 10.1073/pnas.1314575110
[38]

Tonade D, Kern TS. 2021. Photoreceptor cells and RPE contribute to the development of diabetic retinopathy. Progress in Retinal and Eye Research 83:100919

doi: 10.1016/j.preteyeres.2020.100919
[39]

Wu H, Wang M, Li X, Shao Y. 2021. The metaflammatory and immunometabolic role of macrophages and microglia in diabetic retinopathy. Human Cell 34:1617−28

doi: 10.1007/s13577-021-00580-6
[40]

Kaštelan S, Orešković I, Bišćan F, Kaštelan H, Gverović Antunica A. 2020. Inflammatory and angiogenic biomarkers in diabetic retinopathy. Biochemia Medica 30:030502

doi: 10.11613/BM.2020.030502
[41]

Martin PM, Roon P, Van Ells TK, Ganapathy V, Smith SB. 2004. Death of retinal neurons in streptozotocin-induced diabetic mice. Investigative Ophthalmology & Visual Science 45:3330−36

doi: 10.1167/iovs.04-0247
[42]

Zhang J, Wu Y, Jin Y, Ji F, Sinclair SH, et al. 2008. Intravitreal injection of erythropoietin protects both retinal vascular and neuronal cells in early diabetes. Investigative Ophthalmology & Visual Science 49:732−42

doi: 10.1167/iovs.07-0721
[43]

Sohn EH, van Dijk HW, Jiao C, Kok PHB, Jeong W, et al. 2016. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proceedings of the National Academy of Sciences of the United States of America 113:E2655−E2664

doi: 10.1073/pnas.1522014113
[44]

Jonsson KB, Frydkjaer-Olsen U, Grauslund J. 2016. Vascular changes and neurodegeneration in the early stages of diabetic retinopathy: which comes first. Ophthalmic Research 56:1−9

doi: 10.1159/000444498
[45]

Liang D, Qi Y, Liu L, Chen Z, Tang S, et al. 2023. Jin-Gui-Shen-Qi Wan ameliorates diabetic retinopathy by inhibiting apoptosis of retinal ganglion cells through the Akt/HIF-1α pathway. Chinese Medicine 18:130

doi: 10.1186/s13020-023-00840-7
[46]

Jassim AH, Fan Y, Pappenhagen N, Nsiah NY, Inman DM. 2021. Oxidative stress and hypoxia modify mitochondrial homeostasis during glaucoma. Antioxidants & Redox Signaling 35:1341−57

doi: 10.1089/ars.2020.8180
[47]

Nian S, Lo ACY, Mi Y, Ren K, Yang D. 2021. Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets. Eye and Vision 8:15

doi: 10.1186/s40662-021-00239-1
[48]

Shen W, Fruttiger M, Zhu L, Chung SH, Barnett NL, et al. 2012. Conditional Müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model. The Journal of Neuroscience 32:15715−27

doi: 10.1523/JNEUROSCI.2841-12.2012
[49]

Zhou J, Chen B. 2023. Retinal cell damage in diabetic retinopathy. Cells 12:1342

doi: 10.3390/cells12091342
[50]

Kulkarni PG, Mohire VM, Bhaisa PK, Joshi MM, Puranik CM, et al. 2023. Mitofusin-2: Functional switch between mitochondrial function and neurodegeneration. Mitochondrion 69:116−29

doi: 10.1016/j.mito.2023.02.001
[51]

Bianco L, Arrigo A, Aragona E, Antropoli A, Berni A, et al. 2022. Neuroinflammation and neurodegeneration in diabetic retinopathy. Frontiers in Aging Neuroscience 14:937999

doi: 10.3389/fnagi.2022.937999
[52]

Wu JH, Wang YH, Wang W, Shen W, Sang YZ, et al. 2016. miR-18b suppresses high-glucose-induced proliferation in HRECs by targeting IGF-1/IGF1R signaling pathways. International Journal of Biochemistry & Cell Biology 73:41−52

doi: 10.1016/j.biocel.2016.02.002
[53]

Afarid M, Namvar E, Sanie-Jahromi F. 2020. Diabetic retinopathy and BDNF: a review on its molecular basis and clinical applications. Journal of Ophthalmology 2020:1602739

doi: 10.1155/2020/1602739
[54]

Whitmire W, Al-Gayyar MM, Abdelsaid M, Yousufzai BK, El-Remessy AB. 2011. Alteration of growth factors and neuronal death in diabetic retinopathy: what we have learned so far. Molecular Vision 17:300−8

[55]

Kwan CC, Fawzi AA. 2019. Imaging and biomarkers in diabetic macular edema and diabetic retinopathy. Current Diabetes Reports 19:95

doi: 10.1007/s11892-019-1226-2
[56]

Sun Z, Yang D, Tang Z, Ng DS, Cheung CY. 2021. Optical coherence tomography angiography in diabetic retinopathy: an updated review. Eye 35:149−61

doi: 10.1038/s41433-020-01233-y
[57]

Narayanan SP, Shosha E, Palani CD. 2019. Spermine oxidase: a promising therapeutic target for neurodegeneration in diabetic retinopathy. Pharmacological Research 147:104299

doi: 10.1016/j.phrs.2019.104299
[58]

Mallmann F, Canani LH. 2019. Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy. Arquivos Brasileiros de Oftalmologia 82:275−82

doi: 10.5935/0004-2749.20190055
[59]

Amil-Bangsa NH, Mohd-Ali B, Ishak B, Abdul-Aziz CNN, Ngah NF, et al. 2019. Total protein concentration and tumor necrosis factor α in tears of nonproliferative diabetic retinopathy. Optometry and Vision Science 96:934−39

doi: 10.1097/OPX.0000000000001456
[60]

Tamhane M, Cabrera-Ghayouri S, Abelian G, Viswanath V. 2019. Review of biomarkers in ocular matrices: challenges and opportunities. Pharmaceutical Research 36:40

doi: 10.1007/s11095-019-2569-8
[61]

Wang JY, Kwon JS, Hsu SM, Chuang HS. 2020. Sensitive tear screening of diabetic retinopathy with dual biomarkers enabled using a rapid electrokinetic patterning platform. Lab on a Chip 20:356−62

doi: 10.1039/C9LC00975B
[62]

Xuan Q, Ouyang Y, Wang Y, Wu L, Li H, et al. 2020. Multiplatform metabolomics reveals novel serum metabolite biomarkers in diabetic retinopathy subjects. Advanced Science 7:2001714

doi: 10.1002/advs.202001714
[63]

Liu Y, Li J, Ma J, Tong N. 2020. The threshold of the severity of diabetic retinopathy below which intensive glycemic control is beneficial in diabetic patients: estimation using data from large randomized clinical trials. Journal of Diabetes Research 2020:8765139

doi: 10.1155/2020/8765139
[64]

Jonas JB. 2024. Diabetic retinopathy. Asia-Pacific Journal of Ophthalmology 13:100077

doi: 10.1016/j.apjo.2024.100077
[65]

Bryl A, Mrugacz M, Falkowski M, Zorena K. 2022. The effect of diet and lifestyle on the course of diabetic retinopathy-a review of the literature. Nutrients 14:1252

doi: 10.3390/nu14061252
[66]

Chen C, Zhang H, Lan Y, Yan W, Liu S, et al. 2024. Statins as a risk factor for diabetic retinopathy: a Mendelian randomization and cross-sectional observational study. Journal of Translational Medicine 22:298

doi: 10.1186/s12967-024-05097-8
[67]

Stitt AW, Curtis TM, Chen M, Medina RJ, McKay GJ, et al. 2016. The progress in understanding and treatment of diabetic retinopathy. Progress in Retinal and Eye Research 51:156−86

doi: 10.1016/j.preteyeres.2015.08.001
[68]

Kim EJ, Lin WV, Rodriguez SM, Chen A, Loya A, et al. 2019. Treatment of diabetic macular edema. Current Diabetes Reports 19:68

doi: 10.1007/s11892-019-1188-4
[69]

Lanzetta P. 2021. Anti-VEGF therapies for age-related macular degeneration: a powerful tactical gear or a blunt weapon? The choice is ours. Graefe's Archive for Clinical and Experimental Ophthalmology 259:3561−67

doi: 10.1007/s00417-021-05451-2
[70]

Avery RL, Castellarin AA, Steinle NC, Dhoot DS, Pieramici DJ, et al. 2017. Systemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab, and ranibizumab. Retina 37:1847−58

doi: 10.1097/IAE.0000000000001493
[71]

Bressler NM, Beaulieu WT, Glassman AR, Blinder KJ, Bressler SB, et al. 2018. Persistent macular thickening following intravitreous aflibercept, bevacizumab, or ranibizumab for central-involved diabetic macular edema with vision impairment: a secondary analysis of a randomized clinical trial. JAMA Ophthalmology 136:257−69

doi: 10.1001/jamaophthalmol.2017.6565
[72]

Cai S, Bressler NM. 2017. Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T. Current Opinion in Ophthalmology 28:636−43

doi: 10.1097/ICU.0000000000000424
[73]

Estrada CC, Maldonado A, Mallipattu SK. 2019. Therapeutic inhibition of VEGF signaling and associated nephrotoxicities. Journal of the American Society of Nephrology 30:187−200

doi: 10.1681/ASN.2018080853
[74]

Glassman AR, Wells JA, Josic K, Maguire MG, Antoszyk AN, et al. 2020. Five-year outcomes after initial aflibercept, bevacizumab, or ranibizumab treatment for diabetic macular edema (protocol T extension study). Ophthalmology 127:1201−10

doi: 10.1016/j.ophtha.2020.03.021
[75]

Uludag G, Hassan M, Matsumiya W, Pham BH, Chea S, et al. 2022. Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further. Expert Opinion on Biological Therapy 22:1275−91

doi: 10.1080/14712598.2022.2100694
[76]

Pacella F, Romano MR, Turchetti P, Tarquini G, Carnovale A, et al. 2016. An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy. International Journal of Ophthalmology 9:1427−32

doi: 10.18240/ijo.2016.10.10
[77]

Boyer DS, Yoon YH, Belfort R, Bandello F, Maturi RK, et al. 2014. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 121:1904−14

doi: 10.1016/j.ophtha.2014.04.024
[78]

Augustin AJ, Kuppermann BD, Lanzetta P, Loewenstein A, Li XY, et al. 2015. Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema: subgroup analysis of the MEAD study. BMC Ophthalmology 15:150

doi: 10.1186/s12886-015-0148-2
[79]

Hussain RM, Shaukat BA, Ciulla LM, Berrocal AM, Sridhar J. 2021. Vascular endothelial growth factor antagonists: promising players in the treatment of neovascular age-related macular degeneration. Drug Design, Development and Therapy 15:2653−65

doi: 10.2147/DDDT.S295223
[80]

Lin FL, Wang PY, Chuang YF, Wang JH, Wong VHY, et al. 2020. Gene therapy intervention in neovascular eye disease: a recent update. Molecular Therapy 28:2120−38

doi: 10.1016/j.ymthe.2020.06.029
[81]

Porta M, Striglia E. 2020. Intravitreal anti-VEGF agents and cardiovascular risk. Internal and Emergency Medicine 15:199−210

doi: 10.1007/s11739-019-02253-7
[82]

Sahni J, Dugel PU, Patel SS, Chittum ME, Berger B, et al. 2020. Safety and efficacy of different doses and regimens of faricimab vs ranibizumab in neovascular age-related macular degeneration: the AVENUE phase 2 randomized clinical trial. JAMA Ophthalmology 138:955−63

doi: 10.1001/jamaophthalmol.2020.2685
[83]

Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, et al. 2016. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology 123:1351−59

doi: 10.1016/j.ophtha.2016.02.022
[84]

Aref AA, Scott IU, VanVeldhuisen PC, King J, Ip MS, et al. 2021. Intraocular pressure-related events after anti-vascular endothelial growth factor therapy for macular edema due to central retinal vein occlusion or hemiretinal vein occlusion: SCORE2 report 16 on a secondary analysis of a randomized clinical trial. JAMA Ophthalmology 139:1285−91

doi: 10.1001/jamaophthalmol.2021.4395
[85]

Youngblood H, Robinson R, Sharma A, Sharma S. 2019. Proteomic biomarkers of retinal inflammation in diabetic retinopathy. International Journal of Molecular Sciences 20:4755

doi: 10.3390/ijms20194755
[86]

Forrester JV, Kuffova L, Delibegovic M. 2020. The role of inflammation in diabetic retinopathy. Frontiers in Immunology 11:583687

doi: 10.3389/fimmu.2020.583687
[87]

Micera A, Balzamino BO, Di Zazzo A, Dinice L, Bonini S, et al. 2020. Biomarkers of neurodegeneration and precision therapy in retinal disease. Frontiers in Pharmacology 11:601647

doi: 10.3389/fphar.2020.601647
[88]

Chalke SD, Kale PP. 2021. Combinational approaches targeting neurodegeneration, oxidative stress, and inflammation in the treatment of diabetic retinopathy. Current Drug Targets 22:1810−24

doi: 10.2174/1389450122666210319113136
[89]

Semeraro F, Morescalchi F, Cancarini A, Russo A, Rezzola S, et al. 2019. Diabetic retinopathy, a vascular and inflammatory disease: Therapeutic implications. Diabetes & Metabolism 45:517−27

doi: 10.1016/j.diabet.2019.04.002
[90]

Xu J, Chen LJ, Yu J, Wang HJ, Zhang F, et al. 2018. Involvement of advanced glycation end products in the pathogenesis of diabetic retinopathy. Cellular Physiology and Biochemistry 48:705−17

doi: 10.1159/000491897
[91]

Van Bergen T, Etienne I, Cunningham F, Moons L, Schlingemann RO, et al. 2019. The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases. Progress in Retinal and Eye Research 69:116−36

doi: 10.1016/j.preteyeres.2018.10.006
[92]

Buyuktepe TC, Demirel S, Batıoğlu F, Özmert E. 2021. The correlation of inflammation and microvascular changes with diabetic retinal neurodegeneration. Current Eye Research 46:1559−66

doi: 10.1080/02713683.2021.1908567
[93]

Pignataro P, Dicarlo M, Zerlotin R, Zecca C, Dell'Abate MT, et al. 2021. FNDC5/irisin system in neuroinflammation and neurodegenerative diseases: update and novel perspective. International Journal of Molecular Sciences 22:1605

doi: 10.3390/ijms22041605
[94]

Pop-Busui R, Ang L, Holmes C, Gallagher K, Feldman EL. 2016. Inflammation as a therapeutic target for diabetic neuropathies. Current Diabetes Reports 16:29

doi: 10.1007/s11892-016-0727-5
[95]

Antonetti DA, Silva PS, Stitt AW. 2021. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nature Reviews Endocrinology 17:195−206

doi: 10.1038/s41574-020-00451-4
[96]

Eltzschig HK, Carmeliet P. 2011. Hypoxia and inflammation. New England Journal of Medicine 364:656−65

doi: 10.1056/nejmra0910283
[97]

Taylor CT, Colgan SP. 2017. Regulation of immunity and inflammation by hypoxia in immunological niches. Nature Reviews Immunology 17:774−85

doi: 10.1038/nri.2017.103
[98]

Watts ER, Walmsley SR. 2019. Inflammation and hypoxia: HIF and PHD isoform selectivity. Trends in Molecular Medicine 25:33−46

doi: 10.1016/j.molmed.2018.10.006
[99]

Min J, Zeng T, Roux M, Lazar D, Chen L, et al. 2021. The role of HIF1α-PFKFB3 pathway in diabetic retinopathy. The Journal of Clinical Endocrinology and Metabolism 106:2505−19

doi: 10.1210/clinem/dgab362
[100]

Zhao M, Wang S, Zuo A, Zhang J, Wen W, et al. 2021. HIF-1α/JMJD1A signaling regulates inflammation and oxidative stress following hyperglycemia and hypoxia-induced vascular cell injury. Cellular & Molecular Biology Letters 26:40

doi: 10.1186/s11658-021-00283-8
[101]

Midena E, Pilotto E. 2017. Emerging insights into pathogenesis. Developments in Ophthalmology 60:16−27

doi: 10.1159/000459687
[102]

Alfonso-Muñoz EA, Burggraaf-Sánchez de las Matas R, Mataix Boronat J, Molina Martín JC, Desco C. 2021. Role of oral antioxidant supplementation in the current management of diabetic retinopathy. International Journal of Molecular Sciences 22:4020

doi: 10.3390/ijms22084020
[103]

Rossino MG, Dal Monte M, Casini G. 2019. Relationships between neurodegeneration and vascular damage in diabetic retinopathy. Frontiers in Neuroscience 13:1172

doi: 10.3389/fnins.2019.01172
[104]

Sachdeva MM. 2021. Retinal neurodegeneration in diabetes: an emerging concept in diabetic retinopathy. Current Diabetes Reports 21:65

doi: 10.1007/s11892-021-01428-x
[105]

Carpineto P, Toto L, Aloia R, Ciciarelli V, Borrelli E, et al. 2016. Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus. Eye 30:673−79

doi: 10.1038/eye.2016.13
[106]

van Dijk HW, Kok PHB, Garvin M, Sonka M, Devries JH, et al. 2009. Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy. Investigative Ophthalmology & Visual Science 50:3404−9

doi: 10.1167/iovs.08-3143
[107]

van Dijk HW, Verbraak FD, Kok PHB, Stehouwer M, Garvin MK, et al. 2012. Early neurodegeneration in the retina of type 2 diabetic patients. Investigative Ophthalmology & Visual Science 53:2715−19

doi: 10.1167/iovs.11-8997
[108]

Yumnamcha T, Devi TS, Singh LP. 2019. Auranofin mediates mitochondrial dysregulation and inflammatory cell death in human retinal pigment epithelial cells: implications of retinal neurodegenerative diseases. Frontiers in Neuroscience 13:1065

doi: 10.3389/fnins.2019.01065
[109]

Sasaki M, Ozawa Y, Kurihara T, Kubota S, Yuki K, et al. 2010. Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes. Diabetologia 53:971−79

doi: 10.1007/s00125-009-1655-6
[110]

Tien T, Zhang J, Muto T, Kim D, Sarthy VP, et al. 2017. High glucose induces mitochondrial dysfunction in retinal Müller cells: implications for diabetic retinopathy. Investigative Ophthalmology & Visual Science 58:2915−21

doi: 10.1167/iovs.16-21355
[111]

Singh LP, Devi TS. 2021. Potential combination drug therapy to prevent redox stress and mitophagy dysregulation in retinal Müller cells under high glucose conditions: implications for diabetic retinopathy. Diseases 9:91

doi: 10.3390/diseases9040091
[112]

Bowles KR, Silva MC, Whitney K, Bertucci T, Berlind JE, et al. 2021. ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids. Cell 184:4547−4563.e17

doi: 10.1016/j.cell.2021.07.003
[113]

Gan J, Huang M, Lan G, Liu L, Xu F. 2020. High glucose induces the loss of retinal pericytes partly via NLRP3-caspase-1-GSDMD-mediated pyroptosis. BioMed Research International 2020:4510628

doi: 10.1155/2020/4510628
[114]

Huang HW, Yang CM, Yang CH. 2021. Fibroblast growth factor type 1 ameliorates high-glucose-induced oxidative stress and neuroinflammation in retinal pigment epithelial cells and a streptozotocin-induced diabetic rat model. International Journal of Molecular Sciences 22:7233

doi: 10.3390/ijms22137233
[115]

Mesquida M, Drawnel F, Fauser S. 2019. The role of inflammation in diabetic eye disease. Seminars in Immunopathology 41:427−45

doi: 10.1007/s00281-019-00750-7
[116]

Rübsam A, Parikh S, Fort PE. 2018. Role of inflammation in diabetic retinopathy. International Journal of Molecular Sciences 19:942

doi: 10.3390/ijms19040942
[117]

Karlstetter M, Scholz R, Rutar M, Wong WT, Provis JM, et al. 2015. Retinal microglia: Just bystander or target for therapy. Progress in Retinal and Eye Research 45:30−57

doi: 10.1016/j.preteyeres.2014.11.004
[118]

Sorrentino FS, Allkabes M, Salsini G, Bonifazzi C, Perri P. 2016. The importance of glial cells in the homeostasis of the retinal microenvironment and their pivotal role in the course of diabetic retinopathy. Life Sciences 162:54−59

doi: 10.1016/j.lfs.2016.08.001
[119]

Antonetti DA, Barber AJ, Bronson SK, Freeman WM, Gardner TW, et al. 2006. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 55:2401−11

doi: 10.2337/db05-1635
[120]

Ibrahim AS, El-Remessy AB, Matragoon S, Zhang W, Patel Y, et al. 2011. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes. Diabetes 60:1122−33

doi: 10.2337/db10-1160
[121]

Yoshida S, Sotozono C, Ikeda T, Kinoshita S. 2001. Interleukin-6 (IL-6) production by cytokine-stimulated human Müller cells. Current Eye Research 22:341−47

doi: 10.1076/ceyr.22.5.341.5498
[122]

Zong H, Ward M, Madden A, Yong PH, Limb GA, et al. 2010. Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE). Diabetologia 53:2656−66

doi: 10.1007/s00125-010-1900-z
[123]

Liu X, Ye F, Xiong H, Hu D, Limb GA, et al. 2014. IL-1β upregulates IL-8 production in human Müller cells through activation of the p38 MAPK and ERK1/2 signaling pathways. Inflammation 37:1486−95

doi: 10.1007/s10753-014-9874-5
[124]

Boss JD, Singh PK, Pandya HK, Tosi J, Kim C, et al. 2017. Assessment of neurotrophins and inflammatory mediators in vitreous of patients with diabetic retinopathy. Investigative Ophthalmology & Visual Science 58:5594−603

doi: 10.1167/iovs.17-21973
[125]

Pekny M, Wilhelmsson U, Pekna M. 2014. The dual role of astrocyte activation and reactive gliosis. Neuroscience Letters 565:30−38

doi: 10.1016/j.neulet.2013.12.071
[126]

Shin ES, Huang Q, Gurel Z, Sorenson CM, Sheibani N. 2014. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress. PLoS One 9:e103148

doi: 10.1371/journal.pone.0103148
[127]

Sun L, Wang R, Hu G, Liu H, Lv K, et al. 2021. Single cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas. Experimental Eye Research 210:108718

doi: 10.1016/j.exer.2021.108718
[128]

Tonade D, Liu H, Kern TS. 2016. Photoreceptor cells produce inflammatory mediators that contribute to endothelial cell death in diabetes. Investigative Ophthalmology & Visual Science 57:4264−71

doi: 10.1167/iovs.16-19859
[129]

Kern TS, Berkowitz BA. 2015. Photoreceptors in diabetic retinopathy. Journal of Diabetes Investigation 6:371−80

doi: 10.1111/jdi.12312
[130]

Leal EC, Manivannan A, Hosoya KI, Terasaki T, Cunha-Vaz J, et al. 2007. Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy. Investigative Ophthalmology & Visual Science 48:5257−65

doi: 10.1167/iovs.07-0112
[131]

Ghosh S, Karin M. 2002. Missing pieces in the NF-κB puzzle. Cell 109:S81−S96

doi: 10.1016/s0092-8674(02)00703-1
[132]

Khuu LA, Tayyari F, Sivak JM, Flanagan JG, Singer S, et al. 2017. Aqueous humour concentrations of TGF-β, PLGF and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy. Acta Ophthalmologica 95:e206−e211

doi: 10.1111/aos.13230
[133]

Lazzara F, Fidilio A, Platania CBM, Giurdanella G, Salomone S, et al. 2019. Aflibercept regulates retinal inflammation elicited by high glucose via the PlGF/ERK pathway. Biochemical Pharmacology 168:341−51

doi: 10.1016/j.bcp.2019.07.021
[134]

Guo ML, Roodsari SK, Cheng Y, Dempsey RE, Hu W. 2023. Microglia NLRP3 inflammasome and neuroimmune signaling in substance use disorders. Biomolecules 13:922

doi: 10.3390/biom13060922
[135]

Matos AL, Bruno DF, Ambrósio AF, Santos PF. 2020. The benefits of flavonoids in diabetic retinopathy. Nutrients 12:3169

doi: 10.3390/nu12103169
[136]

Karbasforooshan H, Karimi G. 2018. The role of SIRT1 in diabetic retinopathy. Biomedicine & Pharmacotherapy 97:190−94

doi: 10.1016/j.biopha.2017.10.075
[137]

Costa GN, Vindeirinho J, Cavadas C, Ambrósio AF, Santos PF. 2012. Contribution of TNF receptor 1 to retinal neural cell death induced by elevated glucose. Molecular and Cellular Neurosciences 50:113−23

doi: 10.1016/j.mcn.2012.04.003
[138]

Brás JP, Bravo J, Freitas J, Barbosa MA, Santos SG, et al. 2020. TNF-alpha-induced microglia activation requires miR-342: impact on NF-κB signaling and neurotoxicity. Cell Death & Disease 11:415

doi: 10.1038/s41419-020-2626-6
[139]

McGeachy MJ, Cua DJ, Gaffen SL. 2019. The IL-17 family of cytokines in health and disease. Immunity 50:892−906

doi: 10.1016/j.immuni.2019.03.021
[140]

Kummer KK, Zeidler M, Kalpachidou T, Kress M. 2021. Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine 144:155582

doi: 10.1016/j.cyto.2021.155582
[141]

Elsherbiny NM, Sharma I, Kira D, Alhusban S, Samra YA, et al. 2020. Homocysteine induces inflammation in retina and brain. Biomolecules 10:393

doi: 10.3390/biom10030393
[142]

Peng SY, Chuang CC, Hwang YS, Yen CH, Lee CY, et al. 2023. Association of SDF-1 and its receptor CXCR4 polymorphisms on the susceptibility of diabetic retinopathy in the Taiwanese population. Frontiers in Genetics 14:1296773

doi: 10.3389/fgene.2023.1296773
[143]

Abu El-Asrar AM, Alam K, Garcia-Ramirez M, Ahmad A, Siddiquei MM, et al. 2017. Association of HMGB1 with oxidative stress markers and regulators in PDR. Molecular Vision 23:853−71

[144]

Shepherd AJ, Loo L, Gupte RP, Mickle AD, Mohapatra DP. 2012. Distinct modifications in Kv2.1 channel via chemokine receptor CXCR4 regulate neuronal survival-death dynamics. The Journal of Neuroscience 32:17725−39

doi: 10.1523/JNEUROSCI.3029-12.2012
[145]

Deng L, Stafford JH, Liu SC, Chernikova SB, Merchant M, et al. 2017. SDF-1 blockade enhances anti-VEGF therapy of glioblastoma and can be monitored by MRI. Neoplasia 19:1−7

doi: 10.1016/j.neo.2016.11.010
[146]

Wang D, Liu R. 2025. The IL-12 family of cytokines: pathogenetic role in diabetic retinopathy and therapeutic approaches to correction. Naunyn-Schmiedeberg's Archives of Pharmacology 398:125−33

doi: 10.1007/s00210-024-03360-9
[147]

Amoaku WMK, Saker S, Stewart EA. 2015. A review of therapies for diabetic macular oedema and rationale for combination therapy. Eye 29:1115−30

doi: 10.1038/eye.2015.110
[148]

Wong TY, Sun J, Kawasaki R, Ruamviboonsuk P, Gupta N, et al. 2018. Guidelines on diabetic eye care: the international council of ophthalmology recommendations for screening, follow-up, referral, and treatment based on resource settings. Ophthalmology 125:1608−22

doi: 10.1016/j.ophtha.2018.04.007
[149]

Mesquida M, Leszczynska A, Llorenç V, Adán A. 2014. Interleukin-6 blockade in ocular inflammatory diseases. Clinical & Experimental Immunology 176:301−9

doi: 10.1111/cei.12295
[150]

Mesquida M, Molins B, Llorenç V, de la Maza MS, Adán A. 2017. Targeting interleukin-6 in autoimmune uveitis. Autoimmunity Reviews 16:1079−89

doi: 10.1016/j.autrev.2017.08.002
[151]

Vallejo S, Palacios E, Romacho T, Villalobos L, Peiró C, et al. 2014. The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats. Cardiovascular Diabetology 13:158

doi: 10.1186/s12933-014-0158-z
[152]

Lavalette S, Raoul W, Houssier M, Camelo S, Levy O, et al. 2011. Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration. The American Journal of Pathology 178:2416−23

doi: 10.1016/j.ajpath.2011.01.013
[153]

Hernández C, Bogdanov P, Solà-Adell C, Sampedro J, Valeri M, et al. 2017. Topical administration of DPP-IV inhibitors prevents retinal neurodegeneration in experimental diabetes. Diabetologia 60:2285−98

doi: 10.1007/s00125-017-4388-y
[154]

Adhi M, Cashman SM, Kumar-Singh R. 2013. Adeno-associated virus mediated delivery of a non-membrane targeted human soluble CD59 attenuates some aspects of diabetic retinopathy in mice. PLoS One 8:e79661

doi: 10.1371/journal.pone.0079661
[155]

Chen Y, Meng J, Li H, Wei H, Bi F, et al. 2019. Resveratrol exhibits an effect on attenuating retina inflammatory condition and damage of diabetic retinopathy via PON1. Experimental Eye Research 181:356−66

doi: 10.1016/j.exer.2018.11.023
[156]

Du J, Wang Y, Tu Y, Guo Y, Sun X, et al. 2020. A prodrug of epigallocatechin-3-gallate alleviates high glucose-induced pro-angiogenic factor production by inhibiting the ROS/TXNIP/NLRP3 inflammasome axis in retinal Müller cells. Experimental Eye Research 196:108065

doi: 10.1016/j.exer.2020.108065
[157]

Wang L, Sun X, Zhu M, Du J, Xu J, et al. 2019. Epigallocatechin-3-gallate stimulates autophagy and reduces apoptosis levels in retinal Müller cells under high-glucose conditions. Experimental Cell Research 380:149−58

doi: 10.1016/j.yexcr.2019.04.014
[158]

Zhang S, Wu J, Wang L, Mu L, Xu X, et al. 2024. SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment. Frontiers in Molecular Biosciences 11:1366020

doi: 10.3389/fmolb.2024.1366020
[159]

Hong X, Jian Y, Ding S, Zhou J, Zheng X, et al. 2023. Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke. eBioMedicine 87:104406

doi: 10.1016/j.ebiom.2022.104406
[160]

Luo Y, Li C. 2024. Advances in research related to microRNA for diabetic retinopathy. Journal of Diabetes Research 2024:8520489

doi: 10.1155/2024/8520489
[161]

Wang Z, Zhang N, Lin P, Xing Y, Yang N. 2024. Recent advances in the treatment and delivery system of diabetic retinopathy. Frontiers in Endocrinology 15:1347864

doi: 10.3389/fendo.2024.1347864
[162]

Lv K, Ying H, Hu G, Hu J, Jian Q, et al. 2022. Integrated multi-omics reveals the activated retinal microglia with intracellular metabolic reprogramming contributes to inflammation in STZ-induced early diabetic retinopathy. Frontiers in Immunology 13:942768

doi: 10.3389/fimmu.2022.942768
[163]

Yao Y, Li J, Zhou Y, Wang S, Zhang Z, et al. 2023. Macrophage/microglia polarization for the treatment of diabetic retinopathy. Frontiers in Endocrinology 14:1276225

doi: 10.3389/fendo.2023.1276225
[164]

Fan R, Su L, Zhang H, Jiang Y, Yu Z, et al. 2023. Enhanced therapeutic effect of PEDF-loaded mesenchymal stem cell-derived small extracellular vesicles against oxygen-induced retinopathy through increased stability and penetrability of PEDF. Journal of Nanobiotechnology 21:327

doi: 10.1186/s12951-023-02066-z
[165]

Wei L, Sun X, Fan C, Li R, Zhou S, et al. 2022. The pathophysiological mechanisms underlying diabetic retinopathy. Frontiers in Cell and Developmental Biology 10:963615

doi: 10.3389/fcell.2022.963615
[166]

Kempuraj D, Dourvetakis KD, Cohen J, Valladares DS, Joshi RS, et al. 2024. Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders. Frontiers in Cellular Neuroscience 18:1491952

doi: 10.3389/fncel.2024.1491952
[167]

Zhao X, Ling F, Zhang GW, Yu N, Yang J, et al. 2022. The correlation between microRNAs and diabetic retinopathy. Frontiers in Immunology 13:941982

doi: 10.3389/fimmu.2022.941982
[168]

Sun F, Sun Y, Wang X, Zhu J, Chen S, et al. 2024. Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway. Bioactive Materials 33:444−59

doi: 10.1016/j.bioactmat.2023.11.008
[169]

Cohen J, Mathew A, Dourvetakis KD, Sanchez-Guerrero E, Pangeni RP, et al. 2024. Recent research trends in neuroinflammatory and neurodegenerative disorders. Cells 13:511

doi: 10.3390/cells13060511