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Karis Little, Maria Llorian-Salvador, Mei Chen, Heping Xu; A two-stage laser induced model of sub-retinal fibrosis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1263.
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© ARVO (1962-2015); The Authors (2016-present)
Approximately one third of patients with neovascular Age Related Macular Degeneration (nAMD) develop macular fibrosis – a fibrovascular membrane. The pathogenesis of macular fibrosis is not fully understood and currently, there is no treatment for it. This study aimed to develop a model of sub-retinal fibrosis that can recapitulate key features of macular fibrosis in nAMD, e.g., a vascularised subretinal fibrotic membrane.
C57Bl6 mice aged 2-3 months received 3-5 laser burns per eye to induce choroidal neovascularization. 7 days later, a second laser burn was directed to each of the neovascular lesions to induce leakage and/or haemorrhage from new blood vessels. The traditional laser-induced choroidal neovascularization (Laser-CNV) was used as a control. The lesion was monitored over a period of 40 days clinically using OCT and fundus imaging and histologically using H&E and Masson’s trichrome staining. The expression of Collagen 1 (Col-1), fibronectin, CD31 and F4/80 was examined by immunohistochemistry and RT-PCR in retinal/RPE cells at different time points after laser treatment.
A progressive development of subretinal Col-1+ fibrotic lesion was observed and the lesion size peaked 30 days after the 2nd laser treatment (0.18mm2). Col-1+ fibrotic lesion was also observed in the traditional laser-CNV but the lesion size was significantly smaller than the two-stage laser induced fibrosis. Furthermore, the lesions from the two-stage laser treated mice were filled with CD31+ blood vessels accompanied by large number of infiltrating F4/80+ macrophages even 40 days after the laser treatment. Whereas, only a few CD31+ cells and F4/80+ macrophages were observed in the laser-CNV model at this time point.
The two-stage laser treatment induces subretinal fibrovascular membranes that increase in size over 40 days. The model better mimics macular fibrosis in nAMD and is a useful tool for disease mechanism investigation and drug testing.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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