Quantitative regional analysis of vitreoretinal adhesion with age

 描述(申请人提供)：视网膜脱离是光敏细胞与视网膜色素上皮的分离，发生在大约35%的人群中。如果不紧急治疗，可能会导致失明或严重的视力障碍。阻塞性视网膜脱离对儿童和成人都有影响，是由于玻璃体在玻璃体-视网膜界面粘连较强的区域拉动视网膜而引起的。对该界面的结构和蛋白质组成的几项定性研究表明，胶原在粘连过程中起着重要作用。其他研究假设，玻璃体-视网膜交界处丰富的糖蛋白，如纤维连接蛋白和层粘连蛋白，有助于玻璃体-视网膜粘连。尽管在了解玻璃体-视网膜界面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-视网膜粘附力或量化这些蛋白质对粘附力的贡献。这种数据的匮乏阻碍了研究儿童和成人视网膜脱离的数值模型的发展。该建议的目的是测量特定区域和年龄的玻璃体-视网膜粘附性，并量化胶原和糖蛋白对所测量的粘附性的贡献。为了实现这些目标，我们建议利用一种新的定制设备，在不解剖或无意破坏玻璃体-视网膜界面的情况下对视网膜进行粘连剥离测试。附着力将在三个区域进行测量 在两个年龄段(新生儿和成人)的眼球(前部、后部和赤道)。然后，我们建议控制胶原、层粘连蛋白和纤维连接蛋白的浓度和结构完整性，以确定去除这些蛋白如何影响玻璃体-视网膜粘连的测量。操作前后的蛋白质密度将通过透射电子显微镜和免疫组织化学来确定。这项拟议的研究将是第一次对玻璃体-视网膜界面的粘附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，评估与年龄有关的局部粘连机制可以刺激预防和治疗视网膜脱离的新策略，这种策略比目前的护理标准侵入性更小。

 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.