Understanding How Variants in LOXL1 Affect Pseudoexfoliation Glaucoma Risk

The purpose of this project is to determine how variants in the LOXL1 encoding gene alter the protein’s structure and function, thereby altering risk for pseudoexfoliation glaucoma.

Genetic variants in LOXL1 can alter risk for pseudoexfoliation glaucoma (XFG), a blinding disease that affects more than 10 million people. This project seeks to determine how these variants alter the structure and function of the LOXL1 protein. Successful completion of this project will provide a better understanding of how LOXL1 variants contribute to XFG and provide groundwork for therapeutic development.

This project would be the first to characterize the protein structure of LOXL1 with and without pseudoexfoliation glaucoma-associated variants. Results will offer novel insight into how pseudoexfoliation glaucoma-associated variants contribute to the disease by altering interactions with fibulin-5, a protein necessary for proper LOXL1 localization.

The successful completion of this project will result in a better understanding of the molecular mechanisms by which pseudoexfoliation glaucoma-associated variants affect disease risk. This improved knowledge will allow for the development of new therapies that can target these specific mechanisms.