Research led by Rupalatha Maddala, PhD, assistant professor ophthalmology at Duke and colleagues have identified a novel therapeutic target for lowering intraocular pressure (IOP). Their groundbreaking findings were published December 2024 in Journal of Cell Science Insight, and featured on the cover, focuses on a protein structure called the septin cytoskeleton, which may have the potential to be a target for lowering intraocular pressure.
Glaucoma, a leading cause of irreversible blindness worldwide, results from optic nerve damage often associated with elevated intraocular pressure (IOP). Primary open-angle glaucoma (POAG), the most prevalent form of glaucoma in the U.S., is primarily treated by lowering IOP. However, current medical therapies are not always effective in preventing vision loss, highlighting the urgent need for new, mechanism-based treatments.
Maddala and colleagues from Duke, Kaiser Permanente Northern California, the University of California San Francisco, and the University of Rochester Medical Center showed that septins influence actomyosin organization, cell adhesion, contraction, and phagocytosis.
Additionally, they identified elevated expression of a specific septin protein leading to increased IOP in a mouse model, and provided further evidence that a septin-9 gene variant is associated with IOP variation in human subjects.
Notably, they explored a pharmacological approach to target septins, establishing the basis for developing a potential new treatment for glaucoma.
Duke co-authors include, Pratap Challa, MD, professor of ophthalmology; P. Vasantha Rao, PhD, Richard and Kit Barkhouser Distinguished Professor of Ophthalmology; and Nikolai P Skiba, PhD, associate professor of ophthalmology; in collaboration with scientists from Kaiser Permanente Northern California, the University of California San Francisco, and the University of Rochester Medical Center.