DREAM_RPE · Drusen Reconstitution in an Engineered AMD Model using Retinal Pigment Epithelium

Age-related macular degeneration (AMD) is a leading cause of blindness, affecting millions of patients. With the aging population these numbers are predicted to increase exponentially. Drusen Reconstitution in an Engineered AMD Model using Retinal Pigment Epithelium (DREAM-RPE) project aims to develop an recapitulating AMD model, to study early/intermediate stages of disease, by focusing on drusen formation. Drusen is a phenotypical hallmark of AMD, being used for diagnosing and predictive of disease severity and progression. Its implication in AMD-related mechanisms, such as inflammation and oxidative stress, is well established. However, the precise mechanism driving drusen formation remains unclear. Understanding the biogenesis of drusen will lead to a better of AMD and its complex disorder context. Additionally, due to its predictive progression role, I hypothesize that clearing of drusen could lead to delayed disease progression in early/intermediate stages of AMD, providing a potential therapeutical window for patients who currently have no therapeutical options. Currently, there are no suitable in vitro models that replicate this aspect of the AMD. Here I propose to develop an advanced in vitro AMD model, capable of mimicking drusen formation. I will use human RPE cells and incorporate 3D bioprinting to recapitulate the retinal microenvironment, including the Bruch’s membrane, stimulate RPE cells, inducing biological-relevant metabolic activity and drusen formation. Next, I will characterize the mechanisms involved and strive to induce drusen clearing. Co-culturing with microglia, endothelial cells and neuro-retinal cells can gradually be added to the model to increase complexity and human in vivo recapitulation. With DREAM_RPE I aim to address the early/intermediate stages of AMD, with the goal of uncovering therapeutic opportunities that could benefit millions of patients and address a major public health concern.