INNER RETINAL NEURONS IN NORMAL AND DEGENERATING

本研究的主要目的是评估内部视网膜的形态和功能完整性 在视网膜色素变性（RP）的小鼠模型中。RP包括一组遗传性疾病，其特征在于 视网膜光感受器的进行性退化，是失明的主要原因之一 在世界上，没有可用的治疗方法。治疗这种毁灭性疾病的最有希望的策略包括 基因治疗，用人工假体和细胞对内层视网膜进行电刺激， 移植他们的成功部分是基于这样一个假设，即内层视网膜在很大程度上被保存了下来 在光感受器死亡之后，并且对残余细胞的不利影响非常有限。但最近的 文献提供了RP动物模型中负性视网膜重塑的明确证据：视网膜内层 细胞经历严重的形态和功能改变，只有当选择性地 使用研究方法（例如单个细胞的可视化）。 我们的长期目标是确定光感受器的确切时间顺序和机制， 退化会触发对其他视网膜细胞的不良影响，最终完全阻止它们， 识别补救治疗的最佳时间窗口。 本项目基于视网膜的解剖学、电生理学和发育研究， 组织在独特的老鼠模型的RP，重现了一些最常见的形式，人类 疾病现代技术相结合，以揭示内部的形态和功能异常， 视网膜细胞在疾病进展的各个阶段。来自死后RP供体的人视网膜是 也在显微镜下检查。我们的目标是揭示内部视网膜异常，这是共同的， 小鼠和人类形式的视网膜变性，并且独立于潜在的遗传原因发生。 这对于设计突变非依赖性疗法非常重要。

The primary objective of this study is to assess the morphological and functional integrity of the inner retina in mouse models of Retinitis Pigmentosa (RP). RP comprises a group of inherited disorders characterized by progressive degeneration of retinal photoreceptors, and represents one of the major causes of blindness in the world, with no available cure. The most promising strategies to treat this devastating disease include gene therapy, the electrical stimulation of the inner retina with artificial prostheses and cellular transplantation. Their success is partly based upon the assumption that the inner retina is largely preserved following photoreceptor death and that adverse effects upon residual cells are very limited. However, recent literature has provided clear evidence of negative retinal remodeling in animal models of RP: inner retinal cells undergo severe morphological and functional alterations that become evident only when selective methods of investigation (such as the visualization of individual cells) are used. Our long-term objective is to identify the exact time sequence and mechanisms by which photoreceptor degeneration triggers adverse effects upon other retinal cells, ultimately to prevent them completely and to recognize optimal time windows for rescue therapies. The present project is based upon anatomical, electrophysiological and developmental studies of the retinal organization in unique mouse models of RP, which reproduce some of the most frequent forms of the human disease. Modern techniques are combined to reveal morphological and functional abnormalities of inner retinal cells at various stages of the disease progression. Human retinas from postmortem RP donors are also examined microscopically. We aim at uncovering inner retinal abnormalities that are common to both mouse and human forms of retinal degeneration and occur independently of the underlying genetic cause. This is very important to design mutation-independent therapies.