Quantitative regional analysis of vitreoretinal adhesion with age

 描述（由申请人提供）：视网膜脱离是感光细胞与视网膜色素上皮细胞分离，约35%的人群发生视网膜脱离。如果不紧急治疗，它可能导致失明或严重的视力障碍。牵引性视网膜脱离影响儿童和成人，并且由眼睛的玻璃体在玻璃体视网膜界面处的强粘附区域中拉动视网膜引起。一些定性研究的结构和蛋白质组成的这个接口表明，胶原蛋白在粘附中起着重要的作用。其他研究假设，在玻璃体视网膜界面丰富的糖蛋白，如纤连蛋白和层粘连蛋白，有助于玻璃体视网膜粘附。尽管在理解玻璃体视网膜界面处蛋白质的存在和结构方面取得了进展，但还没有直接测量玻璃体视网膜粘附或量化这些蛋白质对粘附力的贡献。这种数据的缺乏阻碍了儿童和成人视网膜脱离研究的数值模型的发展。本提案的目的是测量区域和年龄特异性玻璃体视网膜粘附，并量化胶原蛋白和糖蛋白对测量的粘附特性的贡献。为了实现这些目标，我们建议利用一种新的定制设备，创建用于在视网膜上进行粘附剥离测试，而不会剥离或无意中破坏玻璃体视网膜界面。将在三个区域测量粘附力 眼睛（前，后和赤道）和两个年龄（新生儿和成人）。然后，我们建议操纵胶原蛋白，层粘连蛋白和纤维连接蛋白的浓度和结构完整性，以确定这些蛋白质的去除如何影响玻璃体视网膜粘附的测量。将通过透射电子显微镜和免疫组织化学测定操作前后的蛋白质密度定量。这些研究将是第一次对玻璃体视网膜界面的粘附特性进行生物力学研究，并将为开发预测儿童和成人视网膜脱离的数值工具提供数据。此外，随着年龄的增长，对局部粘连机制的评估可以刺激新的策略，用于预防和治疗视网膜脱离，这比目前的护理标准更具侵入性。

 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.