Angiopoietin-TEK signaling is essential for choriocapillaris development and protects against polypoidal choroidal vasculopathy

The choroid and choriocapillaris (CC) form a unique vascular bed vital for maintenance of the photoreceptors and retinal pigment epithelium (RPE). In addition to its link with age-related macular degeneration (AMD), CC dysfunction is tied to the spectrum of pachychoroid diseases including polypoidal choroidal vasculopathy (PCV). The majority of neovascular AMD seen in patients of Asian and African ancestry is due to PCV and is distinct from the disease found in western patients. Despite this clinical impact, little is known about pathogenesis or optimal treatment of these diseases, or their relationship to classical AMD. Members of the angiopoietin (Angpt)-TEK pathway are essential regulators of the CC. Variants in human TEK and ANGPT2 have been associated with PCV, and a variant in PTPRB has been linked to central serous chorioretinopathy, a related disease. Angpt1 deletion in mice results in CC attenuation and pachyvessel impingement into the CC, characteristic of pachychoroid diseases including PCV. Our proposed studies leverage this new model to gain insights into pachychoroid biology and identify pathways which can be targeted for future therapies.