Elizabeth Wang L&S Biological Sciences
Phenotype changes in Cx50KO via AAV-mediated HMOX1 rescue
Cataract is the clouding of the eye lens due to protein breakdown & aggregation that often occurs when aging. It is a leading cause of blindness, and treatment includes expensive surgery that often introduces the risk of surgical complications. In the Gong lab, prior research has shown that connexin 50 knockout (Cx50KO) mice exhibit smaller lens sizes and mild cataracts. Single cell RNA-sequencing (scRNA-seq) has been performed to study the molecular mechanisms underlying lens growth inhibition and mild cataracts caused by Cx50KO. One of the differentially expressed genes (DEG) identified by scRNA-seq is the HMOX1 gene, which is downregulated in these mice.
HMOX1 codes for HO-1, an antioxidant and heme oxygenase that helps with oxidative stress buildup. HO-1 has been shown to delay senescence, the aging of lenses under oxidative stress. The downregulation of HMOX1 in Cx50KO may potentially explain the mild cataracts found. By utilizing AAV to restore the expression of HMOX1, we hope to look at phenotypic changes to better understand the mechanisms behind HMOX1 in Cx50KO. This project takes a step closer to the goal of developing small molecular therapeutics for cataracts.
Message To Sponsor
Thank you for sponsoring my SURF project. Your support allows undergraduates like me to pursue research despite the current challenges in the field. I am excited to continue my project into the school year, expanding from HMOX1 to additional promising differentially expressed genes whose upregulation in Cx50KO may explain cataract formation. Using AAV to restore Cx50 expression, we aim to clarify how downstream target dysfunction that may promote cataract formation.