VisionGuard · Decoding retinal cell communication to counteract vision loss in aging

The retinal pigment epithelium (RPE) protects our vision through a wide array of essential functions, particularly by supporting the photoreceptors. With aging, the RPE undergoes stress that disrupts these functions and contributes to the development of age-related macular degeneration (AMD). AMD is the leading cause of vision loss in Europe and is projected to affect 77 million people in the EU by 2050.As the disease progresses, communication between the RPE and the underlying blood vessels becomes impaired. The resulting pathological vessel growth marks the most severe stage of AMD, neovascular AMD. If left untreated, this stage leads to photoreceptor damage and vision loss. Current therapies are ineffective for a significant number of patients, highlighting the need for alternative approaches.To communicate effectively with photoreceptors and blood vessels, RPE cells must maintain an intracellular organization that enables the directional secretion of key signaling molecules. This project aims to investigate the underlying disease mechanisms by exploring the mechanistic link between age-related changes in RPE cell morphology, intracellular trafficking and secretion dynamics, and pathological vessel growth.To this end, the project will integrate cutting-edge approaches. I will employ proteomics to analyze changes in RPE secretory profiles, develop an innovative in vitro screening platform to functionally assess candidate proteins for their signaling effects on blood vessels, and validate the therapeutic potential of top candidates in vivo using RNAi-based therapeutics and a mouse model of neovascular AMD. Hosted at Aarhus University, in a leading lab for retinal gene therapy, and building on my expertise in epithelial polarity, in vitro modelling and siRNA screening, this project will provide impactful insights into retinal disease mechanisms and foster innovation in AMD treatment.