The Role of Thrombospondin-1 in Regulating IOP
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 nornal 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.
About the Researcher
Haiyan Gong, MD, PhD, is a professor of Ophthalmology, Anatomy, and Neurobiology at Boston University School of Medicine and a Gold Fellow of ARVO. She graduated from Jiangxi Medical College, Nanchang, China and received her ophthalmology training and Master’s degree from Peking Union Medical College, Beijing, China, and her PhD training in anatomy and neurobiology from Boston University in Boston, MA.
Dr. Gong has been working on the physiology and morphology of the trabecular outflow pathway for three decades and has published 65 scientific articles, invited reviews, and textbook chapters. Her research is focused on understanding the mechanisms that regulate aqueous humor outflow resistance in normal eyes and how this resistance is increased in eyes with POAG, for the purpose of developing insights into new therapeutic strategies to treat this disease.
I received my first BrightFocus Foundation grant in 2001, back when the organization was called the American Health Assistance Foundation. At the time, I was a research assistant professor at Boston University School of Medicine, trying to build my independent research career. That first funding allowed me to hire a post-doctoral fellow to collect preliminary data for future grant applications. I received additional funding from the BrightFocus Foundation from 2005-2009. These three awards have been so valuable for establishing me as an independent researcher in glaucoma and have helped me receive NIH and other industry funding. This funding allowed me to train three post-doctoral fellows, and all of them have become clinician-scientists, who continue to do research in ophthalmology. I received another BrightFocus Foundation grant in 2016, which allowed me to hire a research technician to explore 3D cellular structures and their connections in the eye’s drainage pathway using new technology. The data collected with this award allowed me to receive additional NIH funding to continue the research in this area. The award that I received this year will allow me to support a post-doctoral fellow to explore the role of thrombospondin-1 in regulating intraocular pressure, which has potential to answer some unexplored questions in the field of glaucoma. Additionally, I received funding support from BrightFocus Foundation as co-investigator to perform morphologic studies for the research projects proposed by Dr. Joel Schuman of New York University (2011) and Dr. Yiqin Du of University of Pittsburgh (2014). I deeply appreciate all the support that I received from the BrightFocus Foundation donors.
First published on: July 3, 2019
Last modified on: July 16, 2019