Late stage age-related macular degeneration (AMD) is divided into two types, neovascular or exudative (wet) and atrophic (dry). Wet AMD is increasingly recognized as a group of diseases with differential presentations. In patients of European ancestry, it is characterized by drusen and progression to choroidal neovascularization caused by excessive VEGF. Wet AMD is therefore treated with VEGF inhibitors which have transformed disease prognosis. However, in patients of Asian or African ancestry exudative AMD is most associated with a paucity of drusen and polypoidal choroidal vasculopathy (PCV), a member of the pachychoroid disease spectrum. Despite the prevalence of PCV, this disease remains poorly understood and anti-VEGF therapy is often less effective for these eyes than for those with typical neovascular AMD. Pachychoroid diseases are characterized by the formation of dilated “pachyvessels” originating in the choroid and leading to sub-RPE aneurysmal polyps in PCV. Genetic studies have linked the angiopoietin (Angpt)-TEK endothelial signaling system with PCV and central serous chorioretinopathy, another member of the pachychoroid spectrum. We have discovered that these genes are highly expressed in the choroid and that Angpt1 knockout mice exhibit choriocapillaris attenuation and dilated pachyvessels, confirming that they represent a new animal model of pachychoroid diseases. Furthermore, preliminary single cell RNA sequencing of mouse choroids has revealed that uveal ANGPT1 is essential for maintenance of the choriocapillaris phenotype. In this proposal, we leverage these findings and our new pachychoroid model to fully characterize the role of ANGPT1 signaling in choriocapillaris development and in pathogenesis of pachychoroid and PCV.
|Effective start/end date||6/23/21 → 6/22/22|
- Bayer Consumer Care AG (Quaggin AGMT 7/16/21)
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