The association of more than 140 genes with human photoreceptor degenerations, together with studies of animal models of these monogenic diseases, has provided great insight into their pathogenesis. Here we review the responses of the retina to photoreceptor mutations, including mechanisms of photoreceptor death. We discuss the roles of oxidative metabolism, mitochondrial reactive oxygen species, metabolic stress, protein misfolding, and defects in ciliary proteins, as well as the responses of Müller glia, microglia, and the retinal vasculature. Finally, we report on potential pharmacologic and biologic therapies, the critical role of histopathology as a prerequisite to treatment, and the exciting promise of gene therapy in animal models and in phase 1 trials in humans.

中文翻译：

---

遗传性光感受器变性中视网膜的基因组、生化和细胞反应以及治疗这些疾病的前景。

超过 140 种基因与人类光感受器变性的关联，以及对这些单基因疾病动物模型的研究，为了解其发病机制提供了深刻的见解。在这里，我们回顾了视网膜对光感受器突变的反应，包括光感受器死亡的机制。我们讨论氧化代谢、线粒体活性氧、代谢应激、蛋白质错误折叠和纤毛蛋白缺陷的作用，以及 Müller 胶质细胞、小胶质细胞和视网膜脉管系统的反应。最后，我们报告了潜在的药物和生物疗法、组织病理学作为治疗先决条件的关键作用，以及基因疗法在动物模型和人类 1 期试验中令人兴奋的前景。