Nearly 4.2 million Americans age 40 and older are visually impaired due to retina diseases such as glaucoma, diabetic retinopathy and retinitis pigmentosa. When the human retina is injured, an inflammatory response is invoked leading to scar tissue and a permanent vision loss. On the other hand, the embryonic chick is able to regenerate its retina when injured, through activation of stem/progenitor cells located in the anterior region of the eye, known as the ciliary margin (CM) or by reprogramming of the retinal pigment epithelium (RPE), a tissue located behind the retina. The regeneration from either of these tissues is not spontaneous but must be induced by the addition of factors, such as Fibroblast Growth Factor 2 (FGF2) to the eye after retinectomy (complete removal of the retina). Interestingly, our group recently discovered that inflammatory molecules, such as C3a, could also induce regeneration from the activation of stem/progenitor cells, but the study of RPE reprogramming to regenerate a retina has yet to be explained. The purpose of this study was to determine if C3a signaling can induce chick RPE reprogramming after retina injury. Retinectomies were performed in the presence of C3a, and regeneration was observed. We found that C3a was sufficient to induce RPE reprogramming into neuroepithelium that could later differentiate into all major retinal cell types. RNA sequencing was performed to compare RPE from an E4 developing eye and retinectomy only, to one treated with C3a. We also use RPE treated with FGF2 as a standard for comparison. Results showed an upregulation of genes inflammatory genes such as IL8 and IL16. The upregulation of inflammatory response genes was expected because C3a is an inflammatory response molecule. Interestingly, we saw an upregulation of the transcription factor ASCL1, that plays a key role in neuronal differentiation, in the C3a treated RPE. The study of the mechanisms that allow inflammation to drive repair instead of scar tissue in this model organism, could advance retina repair therapy in humans.
Author: Sydni Rivera
Faculty Advisors: Katia Del Rio-Tsonis, Biology; Erika Grajales Esquivel, Biology; Tracy Haynes, Biology
You must be logged in to post a comment.