Cellular, molecular and physical mechanisms of vitreous structural heterogeneity underlying posterior vitreous detachment

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT This is a K08 award application for Dr. Eileen Hwang, a licensed vitreoretinal surgeon, to independently conduct research studies to identify mechanisms of vitreous aging. The K08 will provide her the support necessary to acquire critical skills in four key career development areas: 1) rabbit models of posterior vitreous detachment; 2) cell-matrix interactions and mechanics; 3) quantitative image analysis; and 4) translational research leadership. To achieve her goals, Dr. Hwang has assembled an interdisciplinary mentoring team comprised of Dr. Brittany Coats (Primary Mentor), an expert in vitreous mechanics, and two Co-Mentors: Dr. Paul Bernstein, an internationally recognized researcher of retinal biochemistry, and Dr. Bryan Jones, a pioneer in retinal connectomics. Complementing these mentors, Dr. Hwang also has a 3 member advisory committee to support her goal of developing models and methods for investigating vitreous aging. Retinal detachment leads to significant morbidity and impacts on quality of life, and new strategies for prevention in high-risk individuals are necessary. There is a critical need to elucidate the mechanisms of posterior vitreous detachment (PVD), the primary cause of retinal detachment. Dr. Hwang's objective is to address the gaps in current knowledge about vitreous structure and aging. Her research will result in preliminary data and models to support future proposals investigating whether biological manipulation of vitreous structure can affect PVD in rabbit models. She proposes the following Specific Aims: Aim 1] Identify the effect of decreasing type IX collagen on vitreous structure; Aim 2] Determine the role of hyalocytes in vitreous aging; and Aim 3] Establish the relationships between eye motion, structural heterogeneity, and PVD. The proposed research is significant because it will: 1) determine whether age-related loss of type IX collagen and increased hyalocyte degradation are pathways that could be blocked to prevent PVD and prevent retinal detachment in high risk individuals, and 2) develop cell culture and animal models of vitreous aging to enable mechanistic and therapeutic studies. The proposed research is innovative because it will apply cellular and molecular specificity to inhibit PVD.