CELL BIOLOGY OF EXPERIMENTAL RETINAL DETACHMENT AND REAT

描述（改编自申请人的摘要）：神经系统脱离 从视网膜色素上皮细胞中分离出的视网膜引起了一系列事件 通过激活早期反应基因，在几分钟内即可检测到。这 导致“视网膜脱离”（RD），一系列特定的细胞 在过去的资助期间详细介绍的事件。这包括 细胞凋亡导致某些受体死亡， 感光细胞，使他们承担一个更原始的结构，变化， 光感受器和Muller细胞（以及其他视网膜细胞， 视网膜中所有非神经细胞类型的增殖， 正常视网膜内外的Muller细胞显著生长 边界即使在成功复位后，视力恢复也往往 而不是最佳的，尤其是如果黄斑受累的话。视网膜脱离 严重的视觉后果，是几种视网膜疾病的并发症 也是致盲性疾病实验疗法的一部分：中央凹 视网膜移植和视网膜下注射载体， 视网膜细胞的转染。因此，定义生物机制 作为对分离和再附着的反应的基础， 优化视网膜的恢复似乎具有明确的医学意义。 本更新申请使用研究者建立的猫模型， 分离/重新附着，以研究重新附着停止或逆转的能力 脱落引起的基本细胞变化;进一步研究 神经营养因子如CNTF和高氧作为减轻退行性 脱离的影响或促进附着后的恢复;并研究 IL-1及其受体拮抗剂（IL-1 ra）在抗肿瘤反应中的作用 支队已知视锥光感受器对光的反应不同。 分离比杆，但在猫锥的研究是困难的， 在灵长类动物中是禁止的。申请人建议制定一项 分离/再附着模型在加州地松鼠，一个物种与 视网膜受损约85%的视锥细胞，这是很容易获得的， 在视觉研究中被广泛使用。申请人将决定 使用ERG测量作为将 视锥光感受器的生理和结构恢复。申请人 相信使用这个模型将有助于理解 锥体并更好地确定治疗（例如，神经营养素，高氧） 减轻视杆细胞为主的视网膜中detetrin的影响， 视锥细胞为主的视网膜申请人认为这些信息将 提供了对视网膜对损伤的反应的更好理解， 从而找到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.