Research progress of subretinal fibrosis associated with neovascular age-related macular degeneration_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Luxi ,  Zhang Peng

Department of Ophthalmology, Affiliated Hospital of Northwest University, Xi′an No. 3 Hospital, Xi′an 710018, China;

Corresponding author：

Zhang Peng, Email: zhangpengfmmu@163.com

Keywords：

Age-related macular degeneration; Subretinal fibrosis; Choroidal neovascularization; Macular neovascularization; Review

DOI：

10.3760/cma.j.cn511434-20230512-00221

Video：

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Abstract Full text Figures/Tables Video References Cited by

The severe visual impairment caused by neovascular age-related macular degeneration (nAMD) is associated with macular neovascularization (MNV) invasion and subretinal fibrosis (SF). Excessive SF can lead to subretinal scarring, irreversible damage to photoreceptors, retinal pigment epithelium, and choroid tissue, resulting in permanent visual impairment in nAMD patients. The pathogenesis of SF is complex, involving many pathological processes such as tissue repair after injury, inflammation, and related signaling pathways and cytokine complex. Current experimental treatments for SF only target inhibition of a single cytokine. Timely and effective inhibition of the formation and progression of MNV and early identification of risk factors for SF are crucial to improving the prognosis of nAMD patients.

Citation： Li Luxi, Zhang Peng. Research progress of subretinal fibrosis associated with neovascular age-related macular degeneration. Chinese Journal of Ocular Fundus Diseases, 2024, 40(3): 239-242. doi: 10.3760/cma.j.cn511434-20230512-00221 Copy

1.	王亚欣, 柯晓云, 陈艳霞, 等. 新生血管性年龄相关性黄斑变性治疗进展[J]. 国际眼科杂志, 2021, 21(10): 1732-1735. DOI: 10.3980/j.issn.1672-5123.2021.10.14.Wang YX, Ke XY, Chen YX, et al. Progress in the treatment of neovascular age-related macular degeneration[J]. Int Eye Sci, 2021, 21(10): 1732-1735. DOI: 10.3980/j.issn.1672-5123.2021.10.14.
2.	李忠庆, 张风禄, 王真真. 玻璃体腔注射雷珠单抗和康柏西普治疗渗出型年龄相关性黄斑变性疗效比较[J]. 国际眼科杂志, 2022, 22(4): 560-563. DOI: 10.3980/j.issn.1672-5123.2022.4.06.Li ZQ, Zhang FL, Wang ZZ. Comparison of efficacy of intravitreal injection of Ranibizumab and Conbercept in the treatment of exudative age-related macular degeneration[J]. Int Eye Sci, 2022, 22(4): 560-563. DOI: 10.3980/j.issn.1672-5123.2022.4.06.
3.	Wang D, Jiang Y, He M, et al. Disparities in the global burden of age-related macular degeneration: an analysis of trends from 1990 to 2015[J]. Curr Eye Res, 2019, 44(6): 657-663. DOI: 10.1080/02713683.2019.1576907.
4.	Spaide RF, Jaffe GJ, Sarraf D, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group[J]. Ophthalmology, 2020, 127(5): 616-636. DOI: 10.1016/j.ophtha.2019.11.004.
5.	Roberts PK, Schranz M, Motschi A, et al. Morphologic and microvascular differences between macular neovascularization with and without subretinal fibrosis[J]. Transl Vis Sci Technol, 2021, 10(14): 1. DOI: 10.1167/tvst.10.14.1.
6.	Cheung CMG, Grewal DS, Teo KYC, et al. The evolution of fibrosis and atrophy and their relationship with visual outcomes in Asian persons with neovascular age-related macular degeneration[J]. Ophthalmol Retina, 2019, 3(12): 1045-1055. DOI: 10.1016/j.oret.2019.06.002.
7.	Teo KYC, Joe AW, Nguyen V, et al. Prevalence and risk factors for the development of physician-graded subretinal fibrosis in eyes treated for neovascular age-related macular degeneration[J]. Retina, 2020, 40(12): 2285-2295. DOI: 10.1097/IAE.0000000000002779.
8.	Roberts PK, Schranz M, Motschi A, et al. Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration[J/OL]. Sci Rep, 2022, 12(1): 88[2022-01-07]. https://pubmed.ncbi.nlm.nih.gov/34996934/. DOI: 10.1038/s41598-021-03716-8.
9.	Roberts PK, Zotter S, Montuoro A, et al. Identification and quantification of the angiofibrotic switch in neovascular AMD[J]. Invest Ophthalmol Vis Sci, 2019, 60(1): 304-311. DOI: 10.1167/iovs.18-25189.
10.	Tenbrock L, Wolf J, Boneva S, et al. Subretinal fibrosis in neovascular age-related macular degeneration: current concepts, therapeutic avenues, and future perspectives[J]. Cell Tissue Res, 2022, 387(3): 361-375. DOI: 10.1007/s00441-021-03514-8.
11.	Holz FG, Sadda SR, Staurenghi G, et al. Imaging protocols in clinical studies in advanced age-related macular degeneration: recommendations from classification of atrophy consensus meetings[J]. Ophthalmology, 2017, 124(4): 464-478. DOI: 10.1016/j.ophtha.2016.12.002.
12.	Janse van Rensburg E, Ryu CL, Rampakakis E, et al. Outer retinal tubulation may result from fibrosed type 2 neovascularization: clinical observations and model of pathogenesis[J]. Retina, 2021, 41(9): 1930-1939. DOI: 10.1097/IAE.0000000000003127.
13.	Kim JH, Kim JW, Kim CG. Comparison of 24-month treatment outcomes between as-needed treatment and switching to treat-and-extend in type 3 macular neovascularization[J/OL]. Sci Rep, 2022, 12(1): 22546[2022-12-29]. https://pubmed.ncbi.nlm.nih.gov/36581675/. DOI: 10.1038/s41598-022-25860-5.
14.	Ishikawa K, Kannan R, Hinton DR. Molecular mechanisms of subretinal fibrosis in age-related macular degeneration[J]. Exp Eye Res, 2016, 142: 19-25. DOI: 10.1016/j.exer.2015.03.009.
15.	Maruyama-Inoue M, Sato S, Yamane S, et al. Variable response of subretinal hyperreflective material to anti-vascular endothelial growth factor classified with optical coherence tomography angiography[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(11): 2089-2096. DOI: 10.1007/s00417-018-4121-7.
16.	Shen M, Zhou H, Lu J, et al. Choroidal changes after anti-VEGF therapy in AMD eyes with different types of macular neovascularization using swept-source OCT angiography[J]. Invest Ophthalmol Vis Sci, 2023, 64(13): 16. DOI: 10.1167/iovs.64.13.16.
17.	Willoughby AS, Ying GS, Toth CA, et al. Subretinal hyperreflective material in the comparison of age-related macular degeneration treatments trials[J]. Ophthalmology, 2015, 122(9): 1846-1853. DOI: 10.1016/j.ophtha.2015.05.042.
18.	Tanaka M, Kakihara S, Hirabayashi K, et al. Adrenomedullin-receptor activity-modifying protein 2 system ameliorates subretinal fibrosis by suppressing epithelial-mesenchymal transition in age-related macular degeneration[J]. Am J Pathol, 2021, 191(4): 652-668. DOI: 10.1016/j.ajpath.2020.12.012.
19.	Lechner J, Chen M, Hogg RE, et al. Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration: complement activation in AMD[J]. Immun Ageing, 2016, 13: 4. DOI: 10.1186/s12979-016-0060-5.
20.	Tobe T, Ortega S, Luna JD, et al. Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model[J]. Am J Pathol, 1998, 153(5): 1641-1646. DOI: 10.1016/S0002-9440(10)65753-7.
21.	Schmidt-Erfurth U, Waldstein SM. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration[J]. Prog Retin Eye Res, 2016, 50: 1-24. DOI: 10.1016/j.preteyeres.2015.07.007.
22.	Jo YJ, Sonoda KH, Oshima Y, et al. Establishment of a new animal model of focal subretinal fibrosis that resembles disciform lesion in advanced age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2011, 52(9): 6089-6095. DOI: 10.1167/iovs.10-5189.
23.	Little K, Ma JH, Yang N, et al. Myofibroblasts in macular fibrosis secondary to neovascular age-related macular degeneration-the potential sources and molecular cues for their recruitment and activation[J]. E Bio Medicine, 2018, 38: 283-291. DOI: 10.1016/j.ebiom.2018.11.029.
24.	Little K, Llorián-Salvador M, Tang M, et al. Macrophage to myofibroblast transition contributes to subretinal fibrosis secondary to neovascular age-related macular degeneration[J]. J Neuroinflammation, 2020, 17(1): 355. DOI: 10.1186/s12974-020-02033-7.
25.	Yi C, Liu J, Deng W, et al. Old age promotes retinal fibrosis in choroidal neovascularization through circulating fibrocytes and profibrotic macrophages[J]. J Neuroinflammation, 2023, 20(1): 45. DOI: 10.1186/s12974-023-02731-y.
26.	Llorián-Salvador M, Byrne EM, Szczepan M, et al. Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells[J]. J Neuroinflammation, 2022, 19(1): 182. DOI: 10.1186/s12974-022-02546-3.
27.	Ma W, Zhang Y, Gao C, et al. Monocyte infiltration and proliferation reestablish myeloid cell homeostasis in the mouse retina following retinal pigment epithelial cell injury[J/OL]. Sci Rep, 2017, 7(1): 8433[2017-08-16]. https://pubmed.ncbi.nlm.nih.gov/28814744/. DOI: 10.1038/s41598-017-08702-7.
28.	Wu J, Chen X, Liu X, et al. Autophagy regulates TGF-β2-induced epithelial-mesenchymal transition in human retinal pigment epithelium cells[J]. Mol Med Rep, 2018, 17(3): 3607-3614. DOI: 10.3892/mmr.2017.8360.
29.	Sato K, Takeda A, Hasegawa E, et al. Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model[J]. Immunol Med, 2018, 41(1): 23-29. DOI: 10.1080/09114300.2018.1451609.
30.	Yi C, Liu J, Deng W, et al. Macrophage elastase (MMP12) critically contributes to the development of subretinal fibrosis[J]. J Neuroinflammation, 2022, 19(1): 78. DOI: 10.1186/s12974-022-02433-x.
31.	Daftarian N, Rohani S, Kanavi MR, et al. Effects of intravitreal connective tissue growth factor neutralizing antibody on choroidal neovascular membrane-associated subretinal fibrosis[J]. Exp Eye Res, 2019, 184: 286-295. DOI: 10.1016/j.exer.2019.04.027.
32.	Bloch SB, Lund-Andersen H, Sander B, et al. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal Ranibizumab[J]. Am J Ophthalmol, 2013, 156(1): 116-124. DOI: 10.1016/j.ajo.2013.02.012.
33.	Jaffe GJ, Ciulla TA, Ciardella AP, et al. Dual antagonism of PDGF and VEGF in neovascular age-related macular degeneration: a phase Ⅱb, multicenter, randomized controlled trial[J]. Ophthalmology, 2017, 124(2): 224-234. DOI: 10.1016/j.ophtha.2016.10.010.
34.	Zhang Y, Liao DY, Wang JM, et al. Inhibitory effect on subretinal fibrosis by anti-placental growth factor treatment in a laser-induced choroidal neovascularization model in mice[J]. Int J Ophthalmol, 2022, 15(2): 189-196. DOI: 10.18240/ijo.2022.02.01.
35.	Shimizu H, Yamada K, Suzumura A, et al. Caveolin-1 promotes cellular senescence in exchange for blocking subretinal fibrosis in age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2020, 61(11): 21. DOI: 10.1167/iovs.61.11.21.
36.	Daftarian N, Baigy O, Suri F, et al. Intravitreal connective tissue growth factor neutralizing antibody or Bevacizumab alone or in combination for prevention of proliferative vitreoretinopathy in an experimental model[J/OL]. Exp Eye Res, 2021, 208: 108622[2021-05-19]. https://pubmed.ncbi.nlm.nih.gov/34022176/. DOI: 10.1016/j.exer.2021.108622.
37.	Chen Q, Jiang N, Zhang Y, et al. Fenofibrate inhibits subretinal fibrosis through suppressing TGF-β-Smad2/3 signaling and Wnt signaling in neovascular age-related macular degeneration[J/OL]. Front Pharmacol, 2020, 11: 580884[2020-11-17]. https://pubmed.ncbi.nlm.nih.gov/33442383/. DOI: 10.3389/fphar.2020.580884.
38.	安宁, 张福燕, 秦波. 单细胞转录组测序在年龄相关性黄斑变性研究中的应用[J]. 国际眼科杂志, 2022, 22(6): 964-968. DOI: 10.3980/j.issn.1672-5123.2022.6.16.An N, Zhang FY, Qin B. Application of single-cell RNA-sequencing in age-related macular degeneration[J]. Int Eye Sci, 2022, 22(6): 964-968. DOI: 10.3980/j.issn.1672-5123.2022.6.16.

1. 王亚欣, 柯晓云, 陈艳霞, 等. 新生血管性年龄相关性黄斑变性治疗进展[J]. 国际眼科杂志, 2021, 21(10): 1732-1735. DOI: 10.3980/j.issn.1672-5123.2021.10.14.Wang YX, Ke XY, Chen YX, et al. Progress in the treatment of neovascular age-related macular degeneration[J]. Int Eye Sci, 2021, 21(10): 1732-1735. DOI: 10.3980/j.issn.1672-5123.2021.10.14.
2. 李忠庆, 张风禄, 王真真. 玻璃体腔注射雷珠单抗和康柏西普治疗渗出型年龄相关性黄斑变性疗效比较[J]. 国际眼科杂志, 2022, 22(4): 560-563. DOI: 10.3980/j.issn.1672-5123.2022.4.06.Li ZQ, Zhang FL, Wang ZZ. Comparison of efficacy of intravitreal injection of Ranibizumab and Conbercept in the treatment of exudative age-related macular degeneration[J]. Int Eye Sci, 2022, 22(4): 560-563. DOI: 10.3980/j.issn.1672-5123.2022.4.06.
3. Wang D, Jiang Y, He M, et al. Disparities in the global burden of age-related macular degeneration: an analysis of trends from 1990 to 2015[J]. Curr Eye Res, 2019, 44(6): 657-663. DOI: 10.1080/02713683.2019.1576907.
4. Spaide RF, Jaffe GJ, Sarraf D, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group[J]. Ophthalmology, 2020, 127(5): 616-636. DOI: 10.1016/j.ophtha.2019.11.004.
5. Roberts PK, Schranz M, Motschi A, et al. Morphologic and microvascular differences between macular neovascularization with and without subretinal fibrosis[J]. Transl Vis Sci Technol, 2021, 10(14): 1. DOI: 10.1167/tvst.10.14.1.
6. Cheung CMG, Grewal DS, Teo KYC, et al. The evolution of fibrosis and atrophy and their relationship with visual outcomes in Asian persons with neovascular age-related macular degeneration[J]. Ophthalmol Retina, 2019, 3(12): 1045-1055. DOI: 10.1016/j.oret.2019.06.002.
7. Teo KYC, Joe AW, Nguyen V, et al. Prevalence and risk factors for the development of physician-graded subretinal fibrosis in eyes treated for neovascular age-related macular degeneration[J]. Retina, 2020, 40(12): 2285-2295. DOI: 10.1097/IAE.0000000000002779.
8. Roberts PK, Schranz M, Motschi A, et al. Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration[J/OL]. Sci Rep, 2022, 12(1): 88[2022-01-07]. https://pubmed.ncbi.nlm.nih.gov/34996934/. DOI: 10.1038/s41598-021-03716-8.
9. Roberts PK, Zotter S, Montuoro A, et al. Identification and quantification of the angiofibrotic switch in neovascular AMD[J]. Invest Ophthalmol Vis Sci, 2019, 60(1): 304-311. DOI: 10.1167/iovs.18-25189.
10. Tenbrock L, Wolf J, Boneva S, et al. Subretinal fibrosis in neovascular age-related macular degeneration: current concepts, therapeutic avenues, and future perspectives[J]. Cell Tissue Res, 2022, 387(3): 361-375. DOI: 10.1007/s00441-021-03514-8.
11. Holz FG, Sadda SR, Staurenghi G, et al. Imaging protocols in clinical studies in advanced age-related macular degeneration: recommendations from classification of atrophy consensus meetings[J]. Ophthalmology, 2017, 124(4): 464-478. DOI: 10.1016/j.ophtha.2016.12.002.
12. Janse van Rensburg E, Ryu CL, Rampakakis E, et al. Outer retinal tubulation may result from fibrosed type 2 neovascularization: clinical observations and model of pathogenesis[J]. Retina, 2021, 41(9): 1930-1939. DOI: 10.1097/IAE.0000000000003127.
13. Kim JH, Kim JW, Kim CG. Comparison of 24-month treatment outcomes between as-needed treatment and switching to treat-and-extend in type 3 macular neovascularization[J/OL]. Sci Rep, 2022, 12(1): 22546[2022-12-29]. https://pubmed.ncbi.nlm.nih.gov/36581675/. DOI: 10.1038/s41598-022-25860-5.
14. Ishikawa K, Kannan R, Hinton DR. Molecular mechanisms of subretinal fibrosis in age-related macular degeneration[J]. Exp Eye Res, 2016, 142: 19-25. DOI: 10.1016/j.exer.2015.03.009.
15. Maruyama-Inoue M, Sato S, Yamane S, et al. Variable response of subretinal hyperreflective material to anti-vascular endothelial growth factor classified with optical coherence tomography angiography[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(11): 2089-2096. DOI: 10.1007/s00417-018-4121-7.
16. Shen M, Zhou H, Lu J, et al. Choroidal changes after anti-VEGF therapy in AMD eyes with different types of macular neovascularization using swept-source OCT angiography[J]. Invest Ophthalmol Vis Sci, 2023, 64(13): 16. DOI: 10.1167/iovs.64.13.16.
17. Willoughby AS, Ying GS, Toth CA, et al. Subretinal hyperreflective material in the comparison of age-related macular degeneration treatments trials[J]. Ophthalmology, 2015, 122(9): 1846-1853. DOI: 10.1016/j.ophtha.2015.05.042.
18. Tanaka M, Kakihara S, Hirabayashi K, et al. Adrenomedullin-receptor activity-modifying protein 2 system ameliorates subretinal fibrosis by suppressing epithelial-mesenchymal transition in age-related macular degeneration[J]. Am J Pathol, 2021, 191(4): 652-668. DOI: 10.1016/j.ajpath.2020.12.012.
19. Lechner J, Chen M, Hogg RE, et al. Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration: complement activation in AMD[J]. Immun Ageing, 2016, 13: 4. DOI: 10.1186/s12979-016-0060-5.
20. Tobe T, Ortega S, Luna JD, et al. Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model[J]. Am J Pathol, 1998, 153(5): 1641-1646. DOI: 10.1016/S0002-9440(10)65753-7.
21. Schmidt-Erfurth U, Waldstein SM. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration[J]. Prog Retin Eye Res, 2016, 50: 1-24. DOI: 10.1016/j.preteyeres.2015.07.007.
22. Jo YJ, Sonoda KH, Oshima Y, et al. Establishment of a new animal model of focal subretinal fibrosis that resembles disciform lesion in advanced age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2011, 52(9): 6089-6095. DOI: 10.1167/iovs.10-5189.
23. Little K, Ma JH, Yang N, et al. Myofibroblasts in macular fibrosis secondary to neovascular age-related macular degeneration-the potential sources and molecular cues for their recruitment and activation[J]. E Bio Medicine, 2018, 38: 283-291. DOI: 10.1016/j.ebiom.2018.11.029.
24. Little K, Llorián-Salvador M, Tang M, et al. Macrophage to myofibroblast transition contributes to subretinal fibrosis secondary to neovascular age-related macular degeneration[J]. J Neuroinflammation, 2020, 17(1): 355. DOI: 10.1186/s12974-020-02033-7.
25. Yi C, Liu J, Deng W, et al. Old age promotes retinal fibrosis in choroidal neovascularization through circulating fibrocytes and profibrotic macrophages[J]. J Neuroinflammation, 2023, 20(1): 45. DOI: 10.1186/s12974-023-02731-y.
26. Llorián-Salvador M, Byrne EM, Szczepan M, et al. Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells[J]. J Neuroinflammation, 2022, 19(1): 182. DOI: 10.1186/s12974-022-02546-3.
27. Ma W, Zhang Y, Gao C, et al. Monocyte infiltration and proliferation reestablish myeloid cell homeostasis in the mouse retina following retinal pigment epithelial cell injury[J/OL]. Sci Rep, 2017, 7(1): 8433[2017-08-16]. https://pubmed.ncbi.nlm.nih.gov/28814744/. DOI: 10.1038/s41598-017-08702-7.
28. Wu J, Chen X, Liu X, et al. Autophagy regulates TGF-β2-induced epithelial-mesenchymal transition in human retinal pigment epithelium cells[J]. Mol Med Rep, 2018, 17(3): 3607-3614. DOI: 10.3892/mmr.2017.8360.
29. Sato K, Takeda A, Hasegawa E, et al. Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model[J]. Immunol Med, 2018, 41(1): 23-29. DOI: 10.1080/09114300.2018.1451609.
30. Yi C, Liu J, Deng W, et al. Macrophage elastase (MMP12) critically contributes to the development of subretinal fibrosis[J]. J Neuroinflammation, 2022, 19(1): 78. DOI: 10.1186/s12974-022-02433-x.
31. Daftarian N, Rohani S, Kanavi MR, et al. Effects of intravitreal connective tissue growth factor neutralizing antibody on choroidal neovascular membrane-associated subretinal fibrosis[J]. Exp Eye Res, 2019, 184: 286-295. DOI: 10.1016/j.exer.2019.04.027.
32. Bloch SB, Lund-Andersen H, Sander B, et al. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal Ranibizumab[J]. Am J Ophthalmol, 2013, 156(1): 116-124. DOI: 10.1016/j.ajo.2013.02.012.
33. Jaffe GJ, Ciulla TA, Ciardella AP, et al. Dual antagonism of PDGF and VEGF in neovascular age-related macular degeneration: a phase Ⅱb, multicenter, randomized controlled trial[J]. Ophthalmology, 2017, 124(2): 224-234. DOI: 10.1016/j.ophtha.2016.10.010.
34. Zhang Y, Liao DY, Wang JM, et al. Inhibitory effect on subretinal fibrosis by anti-placental growth factor treatment in a laser-induced choroidal neovascularization model in mice[J]. Int J Ophthalmol, 2022, 15(2): 189-196. DOI: 10.18240/ijo.2022.02.01.
35. Shimizu H, Yamada K, Suzumura A, et al. Caveolin-1 promotes cellular senescence in exchange for blocking subretinal fibrosis in age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2020, 61(11): 21. DOI: 10.1167/iovs.61.11.21.
36. Daftarian N, Baigy O, Suri F, et al. Intravitreal connective tissue growth factor neutralizing antibody or Bevacizumab alone or in combination for prevention of proliferative vitreoretinopathy in an experimental model[J/OL]. Exp Eye Res, 2021, 208: 108622[2021-05-19]. https://pubmed.ncbi.nlm.nih.gov/34022176/. DOI: 10.1016/j.exer.2021.108622.
37. Chen Q, Jiang N, Zhang Y, et al. Fenofibrate inhibits subretinal fibrosis through suppressing TGF-β-Smad2/3 signaling and Wnt signaling in neovascular age-related macular degeneration[J/OL]. Front Pharmacol, 2020, 11: 580884[2020-11-17]. https://pubmed.ncbi.nlm.nih.gov/33442383/. DOI: 10.3389/fphar.2020.580884.
38. 安宁, 张福燕, 秦波. 单细胞转录组测序在年龄相关性黄斑变性研究中的应用[J]. 国际眼科杂志, 2022, 22(6): 964-968. DOI: 10.3980/j.issn.1672-5123.2022.6.16.An N, Zhang FY, Qin B. Application of single-cell RNA-sequencing in age-related macular degeneration[J]. Int Eye Sci, 2022, 22(6): 964-968. DOI: 10.3980/j.issn.1672-5123.2022.6.16.

Chinese Journal of Ocular Fundus Diseases

Research progress of subretinal fibrosis associated with neovascular age-related macular degeneration

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