Visual impairment due to retina diseases, such as macular degeneration, diabetic retinopathy, and retina detachment, impact over 4 million Americans each year. In the event that the retina is injured, inflammatory responses are activated, leaving a scar that hinders vision. Observations in model organisms, such as the embryonic chick, have shown that the complement component, C3a, an inflammatory response molecule, plays a role in the regeneration of a new retina. Regeneration can occur through activation of stem/progenitor cells in the ciliary margin, located in the anterior portion of the eye, or by retinal pigment epithelium (RPE) reprogramming, located in the posterior portion of the eye. This repair is not spontaneous, and requires the addition of exogenous factors, such as C3a and Fibroblast Growth Factor 2 (FGF2). The lab has studied how C3a has the ability to regenerate a fully differentiated retina, through ciliary regeneration, but the mechanism for regeneration through RPE reprogramming is still unknown. Knowing the mechanisms through which retina regeneration occurs, could help advance retina repair therapy in humans. This project focuses on investigating the role of C3a in the induction of RPE reprogramming, following retina injury in the embryonic chick. This will be analyzed by determining if RPE reprogramming mediated by C3a, relies on FGF2 signaling pathway, or if the two operate independently of each other. Furthermore, we will explore the role of the MAPK signaling pathway on this process. The addition of various inhibitors will be used to make this conclusion. Based on previous studies found on retina regeneration through the ciliary margin, when C3a is added, we hypothesize that C3a will act independently of the FGF2 signaling pathway, but through MAPKs.
Author: Sydni Rivera
Advisors: Erika Esquivel, Dr. Katia Del Rio-Tsonis, Department of Biology