The retina plays a crucial role in the vision process by capturing light and transferring it to the brain as an electric signal where the images are formed. Thus, Retinal diseases are one of the main causes of vision impairment and blindness that can occur from diabetes-related side effects, glaucoma, retinal degeneration, and other eye injuries. Some organisms can regenerate their retina after retinectomy (retina removal); however, humans do not possess this capability. A prime example of this occurring is chicken embryos. In the chicken, after retinectomy, the retinal pigment epithelium (RPE) located behind the retina, undergoes cell reprogramming and becomes a neural retina. Nevertheless, RPE reprogramming only occurs at day 4 of development (E4) and requires the addition of fibroblast growth factor 2 (FGF2). After day 5 of development (E5), the RPE is no longer able to reprogram into neural retina, even in the presence of FGF2. Recently, using various methods to detect RNA molecules in a cell, specifically bulk and single-cell transcriptomics, we found that the Hippo/YAP pathway was upregulated at E5 and that it could negatively regulate RPE cell proliferation affecting its reprogramming capacity. Using TDI-011536, an inhibitor of Hippo/YAP/ pathway, we found that it highly promotes RPE cell proliferation at E4 and E5, but no cell reprogramming. Therefore, we analyzed RPE samples treated with TDI-011536 at E4 and E5 stages by bulk RNAseq, and in addition to activation of cell proliferation genes, we found VSX2 and SOX2, both important for RPE reprogramming and retina identity, were downregulated. Thus, we hypothesize that overexpressing VSX2 and/or SOX2 together with inhibition of YAP/TAZ, will promote RPE reprogramming at E5 even in the absence of FGF2.
Author(s): Caroline Kennelly, Jose Raúl Perez-Estrada, Katia Del Rio-Tsonis
Advisor(s): Katia Del Rio-Tsonis, Biology; Jose Raúl Perez-Estrada, Biology
You must be logged in to post a comment.