CELL BIOLOGY OF EXPERIMENTAL RETINAL DETACHMENT AND REAT

描述（改编自申请人的摘要）：神经元的分离 视网膜色素上皮的视网膜诱导一系列事件 通过激活早期反应基因，可在几分钟内检测到。这个 导致“脱离性视网膜病”（RD），一系列特定的细胞 过去资助期间详细说明的事件。这包括 一些受体因细胞凋亡而死亡，即存活的“解构” 感光细胞，使它们呈现出更原始的结构，变化 光感受器和米勒细胞（以及其他视网膜细胞，如 好），视网膜中所有非神经细胞类型的增殖，以及 正常视网膜内外的 Muller 细胞显着生长 边界。即使成功重新附着后，视力恢复通常也较少 不是最佳的，特别是当涉及黄斑时。视网膜脱离有 严重的视力后果，是多种视网膜疾病的并发症 以及致盲疾病实验疗法的一部分：中心凹 易位、视网膜移植和视网膜下注射载体 视网膜细胞的转染。因此，定义生物学机制 揭示对分离和重新附着的反应并寻找方法 优化视网膜的恢复似乎具有明显的医学意义。 该更新应用程序使用研究者建立的猫科动物模型 分离/重新附着以研究重新附着停止或逆转的能力 分离引起的基本细胞变化；进一步研究使用 CNTF 和高氧等神经营养素可作为减轻退行性病变的方法 分离的效果或促进附着后的恢复；并研究 IL-1 及其受体拮抗剂 (IL-1ra) 在响应中的潜在作用 支队。众所周知，视锥细胞的反应不同 比杆状体更脱离，但猫的视锥细胞的研究很困难，并且 对灵长类动物是禁止的。申请人提议开发一个 加州地松鼠的分离/重新附着模型，该物种具有 约 85% 的视锥细胞受损的视网膜，这是现成的，并且 已广泛应用于视觉研究。申请人将决定 使用 ERG 措施作为关联的手段的可行性 视锥细胞的生理和结构恢复。申请人 相信该模型的使用将有助于理解 锥体并更好地确定是否进行治疗（例如神经营养素、高氧） 减轻视杆细胞主导的视网膜脱离的影响将在 还有视锥细胞为主的视网膜。申请人相信该信息将 提供对视网膜对损伤的反应的更深入的了解，并且可能 导致改善人类视力恢复的方法。

DESCRIPTION (Adapted from the applicant's abstract): Detachment of the neural retina from the retinal pigmented epithelium induces a cascade of events detectable within minutes through the activation of early response genes. This leads to the "retinopathy of detachment" (RD), a series of specific cellular events which have been detailed over the past funding period. This includes the death of some receptors by apoptosis, the "deconstruction" of surviving photoreceptor cells so that they assume a more primitive structure, changes in gene expression in photoreceptors and Muller cells (and other retinal cells as well), the proliferation of all non-neural cell types in the retina, and significant growth of Muller cells within and outside their normal retinal boundaries. Visual recovery even after successful reattachment is often less than optimal, especially if the macula is involved. Retinal detachments have serious visual consequences and are a complication of several retinal diseases as well as part of experimental therapies for blinding diseases: foveal translocation, retinal transplantation and subretinal injections of vectors for transfection of retinal cells. Thus, defining the biological mechanisms underlying the responses to detachment and reattachment and finding methods to optimize recovery of the retina would seem to be of clear medical significance. This renewal application uses the investigator's established feline model of detachment/reattachment to study the ability of reattachment to stop or reverse fundamental cellular changes induced by detachment; to further study the use of neurotrophins such as CNTF and hyperoxia as ways to mitigate the degenerative effects of detachment or promote recovery after attachment; and to study the potential role of IL-1 and its receptor antagonist (IL-1ra) in the response to detachment. It is known that cone photoreceptors react differently to detachment than rods, but the study of cones in cat is difficult, and prohibitive in primates. The applicant proposes to develop a detachment/reattachment model in the California ground squirrel, a species with a retina compromised of about 85 percent cones, that is readily available, and that has been used extensively in vision research. The applicant will determine the feasibility of using ERG measures as a means of correlating the physiological and structural recovery of cone photoreceptors. The applicant believes that the use of this model will aid in understanding the responses of cones and to better determine if treatments (e.g., neurotrophins, hyperoxia) that mitigate the effects of detachments in rod-dominated retinas will do so in a cone-dominant retina as well. The applicant believes this information will provide a greater understanding of the retina's responses to injury, and may lead to ways of improving visual recovery in humans.