Proliferative diabetic retinopathy subtypes defined by immune defense and endothelial mitochondrial dysfunction

Lundeen, E. A. et al. Prevalence of diabetic retinopathy in the US in 2021. JAMA Ophthalmol. 141, 747–754 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Serikbaeva, A., Li, Y., Ma, S., Yi, D. & Kazlauskas, A. Resilience to diabetic retinopathy. Prog. Retin. Eye Res. 101, 101271 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Duh, E. J., Sun, J. K. & Stitt, A. W. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI Insight 2, e93751 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Solomon, S. D. et al. Diabetic retinopathy: a position statement by the American Diabetes Association. Diabetes Care 40, 412–418 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Antonetti, D. A., Klein, R. & Gardner, T. W. Diabetic retinopathy. N. Engl. J. Med. 366, 1227–1239 (2012).

Article  CAS  PubMed  Google Scholar 

Miller, H., Miller, B., Zonis, S. & Nir, I. Diabetic neovascularization: permeability and ultrastructure. Invest. Ophthalmol. Vis. Sci. 25, 1338–1342 (1984).

CAS  PubMed  Google Scholar 

Avery, R. L. et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 113, 1695.e1691–1615 (2006).

Article  Google Scholar 

Gross, J. G. et al. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 136, 1138–1148 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Wells, J. A. et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N. Engl. J. Med. 372, 1193–1203 (2015).

Article  CAS  PubMed  Google Scholar 

Wells, J. A. et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology 123, 1351–1359 (2016).

Article  PubMed  Google Scholar 

Sigurdsson, H., Baines, P. S. & Roxburgh, S. T. Vitrectomy for diabetic eye disease. Eye (Lond) 2, 418–423 (1988).

Article  PubMed  Google Scholar 

Rizzo, S. et al. Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Graefes Arch. Clin. Exp. Ophthalmol. 246, 837–842 (2008).

Article  CAS  PubMed  Google Scholar 

Wang, D. Y., Zhao, X. Y., Zhang, W. F., Meng, L. H. & Chen, Y. X. Perioperative anti-vascular endothelial growth factor agents treatment in patients undergoing vitrectomy for complicated proliferative diabetic retinopathy: a network meta-analysis. Sci. Rep. 10, 18880 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Tsubota, K. et al. Effectiveness of prophylactic intravitreal bevacizumab injection to proliferative diabetic retinopathy patients with elevated preoperative intraocular VEGF in preventing complications after vitrectomy. Clin. Ophthalmol. 13, 1063–1070 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao, X. Y., Xia, S. & Chen, Y. X. Antivascular endothelial growth factor agents pretreatment before vitrectomy for complicated proliferative diabetic retinopathy: a meta-analysis of randomised controlled trials. Br. J. Ophthalmol. 102, 1077–1085 (2018).

Article  PubMed  Google Scholar 

Antonetti, D. A., Silva, P. S. & Stitt, A. W. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat. Rev. Endocrinol. 17, 195–206 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Sivaprasad, S. et al. New targets in diabetic retinopathy: addressing limitations of current treatments through the Sema3A/Nrp1 pathway. Eye (Lond.) https://doi.org/10.1038/s41433-025-03835-w (2025).

Whitcup, S. M., Cidlowski, J. A., Csaky, K. G. & Ambati, J. Pharmacology of corticosteroids for diabetic macular edema. Invest. Ophthalmol. Vis. Sci. 59, 1–12 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rhen, T. & Cidlowski, J. A. Antiinflammatory action of glucocorticoids-new mechanisms for old drugs. N. Engl. J. Med. 353, 1711–1723 (2005).

Article  CAS  PubMed  Google Scholar 

Hata, M. et al. Corticosteroids reduce pathological angiogenesis yet compromise reparative vascular remodeling in a model of retinopathy. Proc. Natl. Acad. Sci. USA 121, e2411640121 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sene, A., Chin-Yee, D. & Apte, R. S. Seeing through VEGF: innate and adaptive immunity in pathological angiogenesis in the eye. Trends Mol. Med. 21, 43–51 (2015).

Article  CAS  PubMed  Google Scholar 

Zhao, B., Zhao, Y. & Sun, X. Mechanism and therapeutic targets of circulating immune cells in diabetic retinopathy. Pharmacol. Res. 210, 107505 (2024).

Article  CAS  PubMed  Google Scholar 

Yamaguchi, M. et al. Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation. Diabetologia 67, 2329–2345 (2024).

Article  CAS  PubMed  Google Scholar 

Zhou, Y. et al. M2 macrophages enhance pathological neovascularization in the mouse model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 56, 4767–4777 (2015).

Article  PubMed  Google Scholar 

Shao, A. et al. C176-loaded and phosphatidylserine-modified nanoparticles treat retinal neovascularization by promoting M2 macrophage polarization. Bioact. Mater. 39, 392–405 (2024).

CAS  PubMed  PubMed Central  Google Scholar 

Binet, F. et al. Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy. Science 369, eaay5356 (2020).

Article  CAS  PubMed  Google Scholar 

Davies, M. H., Stempel, A. J. & Powers, M. R. MCP-1 deficiency delays regression of pathologic retinal neovascularization in a model of ischemic retinopathy. Invest. Ophthalmol. Vis. Sci. 49, 4195–4202 (2008).

Article  PubMed  Google Scholar 

Corano Scheri, K., Lavine, J. A., Tedeschi, T., Thomson, B. R. & Fawzi, A. A. Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator. JCI Insight 8, e172062 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Tamaki, K., Usui-Ouchi, A., Murakami, A. & Ebihara, N. Fibrocytes and fibrovascular membrane formation in proliferative diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 57, 4999–5005 (2016).

Article  CAS  PubMed  Google Scholar 

Hu, Z. et al. Single-cell transcriptomics reveals novel role of microglia in fibrovascular membrane of proliferative diabetic retinopathy. Diabetes 71, 762–773 (2022).

Article  CAS  PubMed  Google Scholar 

Ishikawa, K. et al. Microarray analysis of gene expression in fibrovascular membranes excised from patients with proliferative diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 56, 932–946 (2015).

Article  CAS  PubMed  Google Scholar 

Korhonen, A., Gucciardo, E., Lehti, K. & Loukovaara, S. Proliferative diabetic retinopathy transcriptomes reveal angiogenesis, anti-angiogenic therapy escape mechanisms, fibrosis and lymphatic involvement. Sci. Rep. 11, 18810 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ho, T., Smiddy, W. E. & Flynn, H. W. Jr. Vitrectomy in the management of diabetic eye disease. Surv. Ophthalmol. 37, 190–202 (1992).

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