The Role of Thrombospondin-1 in Regulating Eye Pressure

Glaucoma is a leading cause of blindness worldwide, and a primary risk factor for this disease is abnormally increased pressure inside the eye, which is usually a result of elevated resistance to the drainage of the aqueous humor. Currently, the only way to treat or manage glaucoma is to lower this increased eye pressure. Thrombospondin-1 is a protein expressed in trabecular meshwork of the aqueous drainage pathway of normal eyes, increases in glaucomatous patients, and deleting this protein results in lower eye pressure. The proposed research will investigate the mechanisms by which this protein regulates eye pressure. The findings may lead to novel treatments to lower eye pressure in glaucoma.

This research project aims to determine the role of thrombospondin-1 (TSP1) in regulating intraocular pressure (IOP) and outflow facility. In specific aim 1, we plan to determine whether TSP1 deficiency prevents or reduces steroid-induced ocular hypertension and its underlying mechanisms using a mouse model. In specific aim 2, we plan to determine whether TSP1 reduces outflow facility in ex vivo perfused porcine eyes and what hydrodynamic and morphological changes may be responsible for this reduction. The results from the proposed research will provide a better understanding of the molecular mechanisms involved in IOP regulation and have the potential for developing novel therapeutic strategies by targeting TSP1 to lower IOP in glaucoma.