Identification of Myocilin Posttranslational Modifications and Binding Partners Under Static and Glaucoma-Relevant Mechanical Stretch

Myocilin, a protein molecule associated with two specific forms of glaucoma, is expressed at high levels in the very same eye tissue that appears to malfunction and contribute to ocular hypertension– the most common risk factor—in other types of glaucoma. To this day, the normal function of myocilin in the eye tissue and elsewhere in the body remains unknown. We will use knowledge of the myocilin structure and modern proteomics techniques to identify changes in myocilin and interacting partners under distinct glaucoma-relevant environments. This research will help clarify myocilin function and will lead to new targets for novel anti-glaucoma therapies.

The aim of this research is to comprehend molecular changes in myocilin under experimental conditions in the lab that mimic glaucoma. Myocilin is closely associated with several forms of glaucoma, including early-onset inherited open angle glaucoma, and steroid-induced glaucoma. Myocilin is also expressed at relatively high levels in the eye tissue called the trabecular meshwork (TM). Dysfunction of the TM is believed to bring about elevated ocular pressure, the most common glaucoma risk factor leading to retinal degeneration and vision loss. We will use modern high resolution mass spectrometry techniques to investigate changes in myocilin isolated from the eye-derived cells that maintain the TM tissue. Results of our experiments will provide new insight into glaucoma-relevant changes that will lead to a better understanding of myocilin-associated glaucoma as well the identification of novel targets for anti-glaucoma therapies more generally.