The retina is one of the most important tissues since it is responsible for sight. Injury to the retina can lead to irreparable visual loss. Therefore, studying the process of retinal regeneration in vertebrates that are capable of doing so is important for understanding how the retina can be healed, instead of scarred, after an injury. To this end, the embryonic chick has been identified as a model for retinal regeneration, as until day 4 of embryonic development it is capable of regenerating the retina when treated with certain factors, such as FGF2. FGF2 induces the regeneration of the retina by reprogramming retinal pigment epithelium (RPE) cells, a tissue found behind the retina. However, the exact molecular mechanisms which allow FGF2 to induce RPE reprogramming are not completely understood. We have identified that several genes necessary for RPE reprogramming are also required during cellular reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). In this regard, the hypoxia-inducing factor 1a (HIF1a), a transcriptional factor, is needed for iPSC formation. We hypothesize that HIF1a activity is also required for RPE reprogramming in the context of retina regeneration. In order to test this hypothesis, we will use RPE explants collected from 4-day-old chicken embryos and culture them in the presence and absence of FGF2. In these conditions, we will also induce or inhibit HIF1a activity by adding specific small molecules. In addition, we will use hypoxia conditions to induce HIF1a activity. The presence or absence of retinal growth will help determine HIF1a activity. To characterize the effect of HIF1a on RPE reprogramming, we will also determine the gene expression of genes related to RPE reprogramming and HIF1a activity. Altogether, these findings will help contribute to the understanding of retinal regeneration and directly relates to my interest to become a physician.
Author: Harshavardhan Sanaka
Advisors: Katia Del Rio-Tsonis, Biology; Raul Perez-Estrada, Biology
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