BLR&D Research Career Scientist Award Application (Renewal)

点击翻译按钮获取中文摘要

Project Summary/Abstract This competitive renewal application of my RCS program is focused on a major health problem of vision loss caused by the traumatic eye and brain injury. Both, traumatic eye and brain injuries lead to vision loss and ocular tissue damage that affects veterans’ health and quality of life immensely. Eye and brain trauma are the major cause of vision loss among our veterans and troops engaged in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), New Dawn, and fighting terrorism. Despite using protective gears, eye injuries has risen from 2% in World Wars to 13% in OIF and OEF. Presently, >167,000 Veterans are legally blind, 1.5 million have significantly compromised vision, and >7000 veterans becoming blind each year. Both, traumatic eye and brain injuries are becoming more common among Veterans, active military personnel, and civilians. Also, the population of elderly Veterans continues to increase, and therefore development of novel molecular therapies has become a vital priority of VA research mission. Our research is focused on studying the impact of traumatic eye and brain injuries on vision loss. Our projects are focused towards developing novel nanomedicine and gene-based therapies for treating corneal fibrosis/scarring, uncovering pathophysiologic mechanisms leading to corneal damage, and advancing the mechanistic understanding of corneal wound healing and diabetic retinopathy. The long-range goal of our research is to establish novel efficacious and safe molecular therapies to treat blindness and restore vision in humans and service dogs. We are pursuing four specific projects to achieve our immediate and long-range goals. Project-1 establishes how traumatic eye and brain injuries lead to significant eye defects and blindness acutely and transpire over time by evaluating the impact of chemical/surgical injury on vision loss. Project-2 elucidates the role of epigenetic mechanisms and signaling pathways in the pathogenesis of corneal fibrosis (also called haze or scarring) and other ocular disorders. Project-3 aims to develop novel nanomedicine and gene therapy approaches for treating corneal fibrosis/opacity and restoring vision using established human in vitro, human organ culture, and in vivo animal (rabbit, pig and rodent) models that mimic pathological conditions seen in human patients. Project-4 is focused on studying the pathogenesis processes linked to chemical toxicity and developing multimodal topical ophthalmic drops to mitigate acute and chronic toxicity caused by warfare and toxic chemicals, sulfur mustard, acrolein, chlorine, and hydrogen sulfide. Our laboratory has been very productive during the current RCS funding, and over the years with 140+ peer review journal research articles, 350+ scientific presentations, 10 book chapters, and 47 invited distinguished speaker talks at prestigious institutions including the Harvard Medical School and global scientific meetings including the World Ophthalmology Congress, ARVO, European Vision and Eye Research, International Society for Eye Research, Asia-Pacific Academy of Ophthalmology, Precision Medicine etc. In present RCS cycle, I have delivered 27 international invited talks in UK, France, Italy, Asia, Canada, South Africa, USA etc. and collectively 44 prestigious honors and awards were conferred to my trainees and me. Also, our research has received >8,200 citations with an H-factor of 48 and an i-10-index of 98 (>3000 citations during current RCS cycle). Our eye translational research has led to several important discoveries in the areas of corneal gene therapy, nanomedicine, wound healing, and diabetic retinopathy and has received continuous funding from federal (VA and NIH) and non-federal (foundations, industry etc.) agencies for over $40 million. Our ongoing studies are highly translational and are designed to identify novel therapeutic targets, provide mechanistic insights into the role of the key signaling pathways in the pathophysiology of the corneal diseases, and lead to the development of effective therapies to treat blindness that impact the health of veterans.