As a recipient of a Mentored Clinical Scientist Development Award (K08) I would be able to work directly under the sponsorship of Dr. Andrius Kazlauskas at the Schepens Eye Research Institute in my goal of pursuing a career that combines patient care with research. Working and collaborating on a full-time basis with experienced scientists in an Institute known for its excellence in eye research, will allow me to acquire the basic skills necessary to further understand and investigate molecular mechanisms involved in the pathophysiology of ocular disease, and in particular proliferative vitreoretinopathy (PVR). This would complement and further expand the foundation laid by my prior training, and give me the tools needed to become a productive and significant contributor to my field through years to come. The work proposed in this grant is meant to advance our understanding PVR and the role that platelet derived growth factor (PDGF) plays in this disease. More importantly, allow us to search for potential agents for the treatment of this blinding condition in humans. To this end, this proposal focuses on studying the efficacy and toxicity of STI571, a PDGFR inhibitor, in a rabbit model of PVR. Other agents will also be tested and compared as they become available. The results from this work could potentially lead to future clinical trials that could change how we treat this disease in humans, and improve the prognosis for visual recovery for patients who develop this potentially blinding complication. Furthermore, the knowledge acquired through this work could lead to increased understanding of and future therapies for other blinding intraocular disorders involving fibrous proliferation, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and subretinal fibrosis and disciform scar formation such as seen in macular degeneration (AMD).

National Institute of Health (NIH)
National Eye Institute (NEI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZEY1-VSN (01))
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Mariani, Andrew P
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Schepens Eye Research Institute
United States
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Velez, Gisela; Weingarden, Alexa R; Lei, Hetian et al. (2013) SU9518 inhibits proliferative vitreoretinopathy in fibroblast and genetically modified Muller cell-induced rabbit models. Invest Ophthalmol Vis Sci 54:1392-7
Lei, Hetian; Velez, Gisela; Cui, Jing et al. (2010) N-acetylcysteine suppresses retinal detachment in an experimental model of proliferative vitreoretinopathy. Am J Pathol 177:132-40
Lei, Hetian; Velez, Gisela; Hovland, Peter et al. (2009) Growth factors outside the PDGF family drive experimental PVR. Invest Ophthalmol Vis Sci 50:3394-403
Lei, Hetian; Velez, Gisela; Hovland, Peter et al. (2008) Plasmin is the major protease responsible for processing PDGF-C in the vitreous of patients with proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 49:42-8
Lei, Hetian; Hovland, Peter; Velez, Gisela et al. (2007) A potential role for PDGF-C in experimental and clinical proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 48:2335-42