Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng C-Y, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2:e106–e116.

Article  PubMed  Google Scholar 

Fleckenstein M, Keenan TD, Guymer RH, Chakravarthy U, Schmitz-Valckenberg S, Klaver CC, et al. Age-related macular degeneration. Nat Rev Dis Prim. 2021;7:31.

Article  PubMed  Google Scholar 

Holz FG, Figueroa MS, Bandello F, Yang Y, Ohji M, Dai H, et al. Ranibizumab treatment in treatment-naive neovascular age-related macular degeneration: results from LUMINOUS, a global real-world study. Retina. 2020;40:1673–85.

Article  CAS  PubMed  Google Scholar 

Gonzalez VH, Campbell J, Holekamp NM, Kiss S, Loewenstein A, Augustin AJ, et al. Early and long-term responses to anti–vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data. Am J Ophthalmol. 2016;172:72–79.

Article  CAS  PubMed  Google Scholar 

MASON JO III, White MF, Feist RM, Thomley ML, Albert MA, Persaud TO, et al. Incidence of acute onset endophthalmitis following intravitreal bevacizumab (Avastin) injection. Retina 2008;28:564–7.

Article  PubMed  Google Scholar 

Heier JS, Brown DM, Chong V, Korobelnik J-F, Kaiser PK, Nguyen QD, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–48.

Article  PubMed  Google Scholar 

Mehta H, Tufail A, Daien V, Lee AY, Nguyen V, Ozturk M, et al. Real-world outcomes in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor inhibitors. Prog Retinal Eye Res. 2018;65:127–46.

Article  CAS  Google Scholar 

Martin DF, Maguire MG, Ying Ga, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897–908.

Article  CAS  PubMed  Google Scholar 

Nonnenmacher M, Weber T. Intracellular transport of recombinant adeno-associated virus vectors. Gene Ther. 2012;19:649–58.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang D, Tai PW, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019;18:358–78.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Khanani AM, Kiss S, Turpcu A, Hoang C, Osborne A. Phase 1 study of intravitreal gene therapy ADVM-022 for neovascular AMD (OPTIC Trial). Investigative Ophthalmol Vis Sci. 2020;61:1154–1154.

Google Scholar 

Heier J, Campochiaro P, Ho A. Key takeaways from the RGX-314 phase I/IIa clinical trial for wet AMD (Cohorts 1-5). Am Acad Ophthamol. 2019;10:21.

Google Scholar 

Lebherz C, Maguire A, Tang W, Bennett J, Wilson JM. Novel AAV serotypes for improved ocular gene transfer. J gene Med. 2008;10:375–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Constable IJ, Pierce CM, Lai C-M, Magno AL, Degli-Esposti MA, French MA, et al. Phase 2a randomized clinical trial: safety and post hoc analysis of subretinal rAAV. sFLT-1 for wet age-related macular degeneration. EBioMedicine. 2016;14:168–75.

Article  PubMed  PubMed Central  Google Scholar 

Amaral J, Becerra SP. Effects of human recombinant PEDF protein and PEDF-derived peptide 34-mer on choroidal neovascularization. Investigative Ophthalmol Vis Sci. 2010;51:1318–26.

Article  Google Scholar 

Tombran-Tink J, Chader GG, Johnson LV. PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. Exp eye Res. 1991;53:411–4.

Article  CAS  PubMed  Google Scholar 

Kunchithapautham K, Rohrer B. Sublytic membrane-attack-complex (MAC) activation alters regulated rather than constitutive vascular endothelial growth factor (VEGF) secretion in retinal pigment epithelium monolayers. J Biol Chem. 2011;286:23717–24.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cui B, Guo X, Zhou W, Zhang X, He K, Bai T, et al. Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells. Metabolism. 2023;144:155584.

Article  CAS  PubMed  Google Scholar 

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25:402–8.

Article  CAS  PubMed  Google Scholar 

Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinforma. 2013;14:1–14.

Article  Google Scholar 

Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:W90–W97.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xie Z, Bailey A, Kuleshov MV, Clarke DJ, Evangelista JE, Jenkins SL, et al. Gene set knowledge discovery with Enrichr. Curr Protoc. 2021;1:e90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;102:15545–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27:1739–40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database hallmark gene set collection. Cell Syst. 2015;1:417–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ishikawa K, Kannan R, Hinton DR. Molecular mechanisms of subretinal fibrosis in age-related macular degeneration. Exp Eye Res. 2016;142:19–25.

Article  CAS  PubMed  Google Scholar 

Hughes CP, O’Flynn NM, Gatherer M, McClements ME, Scott JA, MacLaren RE, et al. AAV2/8 anti-angiogenic gene therapy using single-chain antibodies inhibits murine choroidal neovascularization. Mol Ther Methods Clin Dev. 2019;13:86–98.

Article  CAS  PubMed  Google Scholar 

Patel M, Chan C-C. Immunopathological aspects of age-related macular degeneration. Semin Immunopathol. 2008;30:97–110.

Dastgheib K, Green WR. Granulomatous reaction to Bruch’s membrane in age-related macular degeneration. Arch Ophthalmol. 1994;112:813–8.

Article  CAS  PubMed  Google Scholar 

Usui-Ouchi A, Usui Y, Kurihara T, Aguilar E, Dorrell MI, Ideguchi Y, et al. Retinal microglia are critical for subretinal neovascular formation. JCI insight. 2020;5:e137317.

Article  PubMed  PubMed Central  Google Scholar 

Sun Y, Lin Z, Liu C-H, Gong Y, Liegl R, Fredrick TW, et al. Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos. J Exp Med. 2017;214:1753–67.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simons M, Eichmann A. Molecular controls of arterial morphogenesis. Circulation Res. 2015;116:1712–24.

Article  CAS  PubMed