Abstract
Purpose :
In neovascular age-related macular degeneration (nAMD), retinal pigment epithelial (RPE) elevations due to drusen deposits, pachychoroids, and choroidal neovascularization (CNV) proliferation are observed histologically. It is thought that mechanical stress on the RPE is involved in the development of CNV, but this pathogenesis in vivo has not yet been elucidated. Therefore, using the animal model we previously reported, we investigated the changes in angiogenesis-related factors resulting from mechanical stress applied to the RPE and examined the response to anti-vascular endothelial growth factor (VEGF) antibodies.
Methods :
8-week-old male C57BL/6J mice were used. Glass beads ranging from 0.8 to 1.2 mm in diameter were inserted behind the eyeball subconjunctivally (each on the supratemporal and inferior nasal sides) so that to provide mechanical stretch to the RPE transsclerally. Three days after bead insertion, anti-VEGF-A antibody (AF-493-NA), aflibercept, and faricimab were injected intravitreal. On the 6th day after the injection, the eyeballs were enucleated and ocular tissue (including RPE and choroid) was collected, and the expression of VEGF was evaluated using Western Blot analysis.
Results :
Elevated VEGF expression in the ocular tissue due to beads insertion was suppressed by any of the injected anti-VEGF antibodies. In the future, it is necessary to investigate changes over time after anti-VEGF antibody injection and changes depending on antibody concentration.
Conclusions :
In the present study, we attempted to apply mechanical stress to RPE in an animal model using beads from outside the eye. The elevation of VEGF expression similar to nAMD that occurred in this animal model was suppressed by anti-VEGF antibodies. It is expected that this exprerimental system may be useful for analysing the mechanisms of the progression of nAMD in the future.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.