Prof. Raquel Lieberman, Georgia Tech

 Structural and biophysical insights into the glaucoma-associated olfactomedin domain of myocilin

School Colloquium

The inherited form of open angle glaucoma, a disorder characterized by increased intraocular pressure and retina degeneration, is linked to mutations in the olfactomedin (OLF) domain of the myocilin gene. Myocilin variants accumulate within trabecular meshwork cells instead of being secreted to the extracellular matrix that regulates aqueous humor flow and controls eye pressure. Myocilin glaucoma pathogenesis appears to originate from a trafficking defect in which myocilin variants are inefficiently cleared in the endoplasmic reticulum, leading to toxic intracellular aggregates and cell death. We developed the first preparative recombinant expression and purification system for the myocilin OLF domain, and have investigated biophysical properties of wild type and ~25 disease-causing variants. Our quantitative insight into the stability of disease-causing OLF variants and elucidation of key structural features of OLF monomers and aggregates places myocilin glaucoma squarely within the context of other diseases of protein misfolding, paving new avenues for glaucoma therapeutics.

 For more information contact Prof. Charles Liotta (404-894-8222).