Mitchell P, Liew G, Gopinath B, Wong TY (2018) Age-related macular degeneration. Lancet 392:1147–1159. https://doi.org/10.1016/S0140-6736(18)31550-2

Article  PubMed  Google Scholar 

Bhutto I, Lutty G (2012) Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex. Mol Aspects Med 33:295–317. https://doi.org/10.1016/j.mam.2012.04.005

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao S, Lan X, Wu J, Yue S, Zhang H, Wu Q, Zhang G, Liu L (2019) Protocol of global incidence and progression of age-related macular degeneration: a systematic review. Medicine 98:e14645. https://doi.org/10.1097/MD.0000000000014645

Article  PubMed  PubMed Central  Google Scholar 

Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng C-Y, Wang TY (2014) Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2:e106–e116. https://doi.org/10.1016/s2214-109x(13)70145-1

Article  PubMed  Google Scholar 

Mones J, Singh RP, Bandello F, Souied E, Liu X, Gale R (2020) Undertreatment of neovascular age-related macular degeneration after 10 years of anti-vascular endothelial growth factor therapy in the real world: the need for a change of mindset. Ophthalmologica 243:1–8. https://doi.org/10.1159/000502747

Article  PubMed  Google Scholar 

Choudhary M, Malek G (2019) A review of pathogenic drivers of age-related macular degeneration, beyond complement, with a focus on potential endpoints for testing therapeutic interventions in preclinical studies. Adv Exp Med Biol 1185:9–13. https://doi.org/10.1007/978-3-030-27378-1_2

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marazita MC, Dugour A, Marquioni-Ramella MD, Figueroa JM, Suburo AM (2016) Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: implications for age-related macular degeneration. Redox Biol 7:78–87. https://doi.org/10.1016/j.redox.2015.11.011

Article  CAS  PubMed  Google Scholar 

Potilinski MC, Tate PS, Lorenc VE, Gallo JE (2021) New insights into oxidative stress and immune mechanisms involved in age-related macular degeneration tackled by novel therapies. Neuropharmacology 188:108513. https://doi.org/10.1016/j.neuropharm.2021.108513

Article  CAS  PubMed  Google Scholar 

Datta S, Cano M, Ebrahimi K, Wang L, Handa JT (2017) The impact of oxidative stress and inflammation on RPE degeneration in nonneovascular AMD. Prog Retin Eye Res 60:201–218. https://doi.org/10.1016/j.preteyeres.2017.03.002

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marquioni-Ramella MD, Suburo AM (2015) Photo-damage, photo-protection and age-related macular degeneration. Photochem Photobiol Sci 14:1560–1577. https://doi.org/10.1039/c5pp00188a

Article  CAS  PubMed  Google Scholar 

Plafker SM, O’Mealey GB, Szweda LI (2012) Mechanisms for countering oxidative stress and damage in retinal pigment epithelium. Int Rev Cell Mol Biol 298:135–177. https://doi.org/10.1016/B978-0-12-394309-5.00004-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Crabb JW, Miyag M, Gu X et al (2002) Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. P Natl Acad Sci USA 99:14682–14687. https://doi.org/10.1073/pnas.222551899

Article  CAS  Google Scholar 

Crabb JW (2014) The proteomics of drusen. Cold Spring Harb Perspect Med 4:1–14. https://doi.org/10.1101/cshperspect.a017194

Article  CAS  Google Scholar 

Rozinga MP, Durhuus JA, Nielsen MK, Subhi Y, Kirkwood TB, Westendorp RG, Sørensen TL (2020) Age-related macular degeneration: a two-level model hypothesis. Prog Retin Eye Res 76:100825. https://doi.org/10.1016/j.preteyeres.2019.100825

Article  Google Scholar 

Wurm R, Resl M, Neuhold S, Prager R, Brath H, Francesconi C, Vila G, Strunk G, Clodi M, Luger A et al (2016) Cardiovascular safety of metformin and sulfonylureas in patients with different cardiac risk profiles. Heart 102:1544–1551. https://doi.org/10.1136/heartjnl-2015-308711

Article  CAS  PubMed  Google Scholar 

Maruthur NM, Tseng E, Hutfless S, Wilson L, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal J, Bolen S (2016) Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes. Ann Intern Med 164:740–748. https://doi.org/10.7326/m15-2650

Article  PubMed  Google Scholar 

Chen J, Han J, Li Y, Liu X, Zhou T, Sun H, Edwards P, Gao H, Yu F-S, Qiao X (2018) Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo. PLoS One 13:1–16. https://doi.org/10.1371/journal.pone.0193031

Article  CAS  Google Scholar 

Xavier DO, Amaral LS, Gomes MA, Rocha MA, Campos PR, Cota BDCV, Tafuri LSA, Paiva AMR, Silva JH, Andrade SP et al (2010) Metformin inhibits inflammatory angiogenesis in a murine sponge model. Biomed Pharmacother 64:220–225. https://doi.org/10.1016/j.biopha.2009.08.004

Article  CAS  PubMed  Google Scholar 

Tan BK, Adya R, Chen J, Farhatullah S, Heutling D, Mitchell D, Lehnert H, Raneva HS (2009) Metformin decreases angiogenesis via NF-κB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1. Cardiovasc Res 83:566–574. https://doi.org/10.1093/cvr/cvp131

Article  CAS  PubMed  Google Scholar 

Esfahanian N, Shakiba Y, Nikbin B, Soraya H, Maleki-Dizaji N, Ghazi-Khansari M, Garjani A (2012) Effect of metformin on the proliferation, migration, and MMP-2 and -9 expression of human umbilical vein endothelial cells. Mol Med Rep 5:1068–1074. https://doi.org/10.3892/mmr.2012.753

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brown EE, Ball JD, Chen Z, Khurshid GS, Prosperi M, Ash JD (2019) The common antidiabetic drug metformin reduces odds of developing age-related macular degeneration. Invest Ophthalmol Vis Sci 60:1470–1477. https://doi.org/10.1167/iovs.18-26422

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen Y, Shen Y, Lai Y, Wang C, Lin K, Feng S-C, Liang C-Y, Wei L-C, Chou P (2019) Association between metformin and a lower risk of age-related macular degeneration in patients with type 2 diabetes. J Ophthalmol 2019:1649156. https://doi.org/10.1155/2019/1649156

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stewart JM, Lamy R, Wu F, Keenan JD (2020) Relationship between oral metformin use and age-related macular degeneration. Ophthalmol Retina 4:1118–1119. https://doi.org/10.1016/j.oret.2020.06.003

Article  PubMed  PubMed Central  Google Scholar 

Wang Z, Ma C, Meng CJ et al (2012) Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model. J Pineal Res 53:129–137. https://doi.org/10.1111/j.1600-079X.2012.00978

Article  CAS  PubMed  Google Scholar 

Cuadrado A, Manda G, Hassan A et al (2018) Transcription factor Nrf2 as a therapeutic target for chronic diseases: a systems medicine approach. Pharmacol Rev 70:348–383. https://doi.org/10.1124/pr.117.014753

Article  CAS  PubMed  Google Scholar 

He M, Pan H, Chang RC, So KF, Brecha NC, Pu M (2014) Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage. PLoS One 9:e84800. https://doi.org/10.1371/journal.pone.0084800

Article  CAS  PubMed  PubMed Central  Google Scholar 

Salgado D, Forrer RS, Spiess BM (2000) Activities of NADPH-dependent reductases and sorbitol dehydrogenase in canine and feline lenses. Am J Vet Res 6:1322–1324. https://doi.org/10.2460/ajvr.2000.61.1322

Article  Google Scholar 

Saha S, Buttari B, Panieri E, Profumo E, Saso L (2020) An overview of Nrf2 signaling pathway and its role in inflammation. Molecules 25:1–31. https://doi.org/10.3390/molecules25225474

Article  CAS  Google Scholar 

Yiu G, Tieu E, Nguyen AT, Wong B, Smit-McBride Z (2016) Genomic disruption of VEGF-A expression in human retinal pigment epithelial cells using CRISPR/Cas9 endonuclease. Invest Ophthalmol Vis Sci 57:5490–5497. https://doi.org/10.1167/iovs.16-20296

Article  CAS  PubMed  PubMed Central  Google Scholar 

Blitzer AL, Ham SA, Colby KA, Skondra D (2021) Association of metformin use with age-related macular degeneration: a case-control study. JAMA Ophthalmol 139:302–309. https://doi.org/10.1001/jamaophthalmol.2020.6331

Article  PubMed  PubMed Central  Google Scholar 

Jiang J, Chen Y, Zhang H, Yuan W, Zhao T, Wang N, Fan G, Zheng D, Wang Z (2022) Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: a retrospective study. BMJ Open 12:e054420. https://doi.org/10.1136/bmjopen-2021-054420

Article  PubMed  PubMed Central  Google Scholar 

Shao Y, Wang M, Zhu Y, Li X, Liu J (2022) Association of metformin treatment with enhanced effect of anti-VEGF agents in diabetic macular edema patients. Acta Diabetol 59:553–559. https://doi.org/10.1007/s00592-021-01833-4

Article  CAS  PubMed  Google Scholar