Uncovering the Developmental Mechanism of Chorioretinal Anastomoses
MentorDouglas Gould, PhD
We investigate the developmental mechanism driving chorioretinal anastomoses (CRA) - lesions characterizing a challenging and often resistant subtype of neovascular age-related macular degeneration. The aims of our study are to (1) optimize an advanced imaging method to peer deep into the living eye with cellular resolution and the ability to measure microvascular blood flow; (2) employ this method in a genetic model of neovascular age-related macular degeneration (AMD) to characterize the arteriovenous identity and blood flow of CRA; and (3) to uncover the developmental origin of CRA. Completion of these aims will enable a broadly powerful imaging tool for the AMD research community and increase our fundamental understanding of a challenging form of neovascular AMD.
A challenging subtype of neovascular age-related macular degeneration is distinguished by vascular proliferation in the retina and choroid, resulting in chorioretinal anastomoses (CRA). CRA can be resistant to existing therapies, and their developmental mechanism remains unknown. Our project has two major innovations: (1) we optimize a powerful approach for imaging of chorioretinal vascular development and use this to study the formation of CRA, and (2) we uncover a potentially novel role for arteriovenous identity and remodeling in the pathogenesis of CRA. Completion of this project will enable a powerful intravital imaging approach for studying chorioretinal biology and vascular dynamics, which will be broadly useful to the age-related macular degeneration research community. Additionally, this project will uncover a potential role for arteriovenous identity and remodeling in the pathogenesis of chorioretinal anastomoses and neovascular age-related macular degeneration, helping to lay a conceptual framework for new therapeutic avenues for treatment-resistant disease.