HUMAN AND ANIMAL RETINAS--CELL BIOLOGY OF THE IPM

本提案的广泛、长期目标是阐明 特异性感光细胞间基质结构与功能关系 (IPM)大分子，特别是当它们涉及到支持 视网膜感光细胞的维持、健康和存活 和视网膜色素上皮（RPE）。 在即将到来的赠款期间， 重点将放在GP 147上，这是一种不溶性糖蛋白， IPM和透明质酸（HA），最近被确定为 不溶性IPM。 具体目标：具体目标1：测试 假设GP 147在上一个资助期内被确定为 人视网膜不溶性IPM中的主要糖蛋白， 差异合成并分布在视杆和视锥周围。 重点是确定GP 147在黄斑中的分布， 周边视网膜，识别负责其合成的细胞， 糖缀合物的结构和GP 147基因的分离。 具体目的2：检验小鼠IPM含有 与GP 147同源。 重点是表达和综合 GP 147在视网膜发育过程中的作用及其更新速率 在成人中。 具体目标3：检验GP 147和 透明质酸（HA），也在前一个gant时期被确定为 不溶性IPM的组成部分，形成缔合相互作用。 重点 确定GP 147是否通过以下方式与IPM相互作用 与HA的联系 具体目标4：检验以下假设： 光感受器和/或RPE参与合成 透明质酸（HA）存在于不溶性IPM中。 强调的是 IPM HA的细胞起源和发育。 由于IPM的战略位置， 可能是影响这种界面的遗传疾病的目标， 可能包括视网膜脱离、中心性浆液性视网膜病变、某些形式 黄斑变性和色素性视网膜炎

The broad, long-term objective of this proposal is to elucidate the structure-function relationships of specific interphotoreceptor matrix (IPM) macromolecules, especially as they relate to supporting the maintenance, health and survival of photoreceptor cells of the retina and retinal pigment epithelium (RPE). During the upcoming grant period, the focus will be on GP147, a prominent glycoprotein in the insoluble IPM, and hyaluronan (HA), recently identified as a component of the insoluble IPM. The Specific Aims are: Specific Aim 1: To test the hypothesis that GP147, identified during the previous grant period as a major glycoprotein in the insoluble IPM of human retina, is differentially synthesized and distributed around rods and cones. Emphasis is on determining the distribution of GP147 in macula and peripheral retina, identifying the cells responsible for its synthesis, the structure of the glycoconjugates and isolation of the GP147 gene. Specific Aim 2: To test the hypothesis that the mouse IPM contains a homologue to GP147. Emphasis is on the expression and synthesis of GP147 during retinal development and in the rate of turnover of GP147 in the adult. Specific Aim 3: To test the hypothesis that GP147 and hyaluronan (HA), also identified during the previous gant period as a component of the insoluble IPM, form associative interactions. Emphasis is on determining whether GP147 interacts with the IPM through associations with HA. Specific Aim 4: To test the hypothesis that photoreceptors and/or the RPE are involved in the synthesis of hyaluronan (HA) present in the insoluble IPM. Emphasis is on the cellular origin and development of IPM HA. Because of the strategic location of the IPM, components of this matrix may be targets for genetic disorders that affect this interface which may include retinal detachment, central serous retinopathy, some forms of macular degeneration and retinitis pigmentosa.