Quantitative regional analysis of vitreoretinal adhesion with age

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): Retinal detachment is the separation of the photosensitive cells from the retinal pigment epithelium and occurs in approximately 35% of the population. It can lead to blindness or severe visual impairment if not treated urgently. Tractiona retinal detachment affects both children and adults, and is caused by the vitreous of the eye pulling on the retina in regions of strong adhesion at the vitreoretinal interface. Several qualitative studies on the structural and protein composition of this interface suggest that collagen plays an important role in adhesion. Other studies hypothesize that abundant glycoproteins at the vitreoretinal interface, such as fibronectin and laminin, contribute to vitreoretinal adhesion. Despite the advancement in understanding the presence and structure of proteins at the vitreoretinal interface, there has been no direct measurement of vitreoretinal adhesion or quantification of the contribution of these proteins to adhesive forces. This paucity of data hinders the development of numerical models for investigating retinal detachment in children and adults. The objectives of this proposal are to measure region- and age-specific vitreoretinal adhesion and quantify the contribution of collagen and glycoproteins to the measured adhesive properties. To achieve these objectives, we propose to capitalize on a novel custom-made device created to perform adhesion peel tests on the retina without dissection or unintentional disruption of the vitreoretinal interface. Adhesion will be measured in three regions of the eye (anterior, posterior and equator) and in two ages (newborn and adult). Then, we propose to manipulate the concentration and structural integrity of collagen, laminin and firbronectin to determine how removal of these proteins affects measurements of vitreoretinal adhesion. Quantification of protein density before and after manipulation will be determined through transmission electron microscopy and immunohistochemistry. The proposed studies will be the first biomechanical investigation into the adhesive properties of the vitreoretinal interfac and will provide data to develop numerical tools for predicting retinal detachment in children and adults. Furthermore, evaluation of regional mechanisms of adhesion with age can spur novel strategies for prevention and treatment of retinal detachment that is less invasive than the current standard of care.