Pathology and treatment of mouse models of dominant retinal disease

遗传性视网膜疾病影响我们最宝贵的感觉，视力，约1/3000的人口。这些疾病中的许多导致视力完全丧失失明，不幸的是，目前还没有有效的治疗方法。开发治疗方法的一个主要困难是无法从患者身上采集视网膜组织样本，以充分了解疾病的发展过程或测试可能进一步损害有限视力的新治疗方法。动物模型的使用避免了这些问题，但要有意义，它们需要准确地模拟人类疾病。这意味着必须研究相同的基因突变。这种突变通常在自然界中找不到，因此必须在动物中靶向与人类相同的基因，以便引入相同的突变。这些都是复杂、耗时和昂贵的实验，因此充分利用这些人类疾病模型非常重要。我们已经建立了两个这样的模型，其中人类基因突变负责基本的视觉过程，导致视网膜中感光细胞的损失。我们建议使用这些模型来详细了解视网膜变性的过程，并随后评估潜在的治疗方案，其中包括测试各种药物，生长因子和使用病毒载体递送到眼睛的基因替代疗法。这将使我们能够确定患者的治疗方法，并为临床试验迈出第一步。

Hereditary retinal disease affects our most precious sense, sight, in about 1 in 3000 of the population. Many of these disorders cause complete loss of vision blindness and, unfortunately, there is as yet no effective treatment. A major difficulty in developing treatments is the inability to sample retinal tissues from patients in order to fully understand how the disease develops or to test novel treatments that may further compromise limited vision. The use of animal models avoids these problems but, to be meaningful, they need to accurately mimic the human disorder. This means that the same gene mutation must be studied. Such mutations are generally not found in nature so the same gene as in human must be targeted in the animal so that the same mutation is introduced. These are complex, time-consuming and expensive experiments, so it is important that such models of human disease are fully exploited. We have already generated two such models with human mutations in genes responsible for basic visual processes resulting in the loss of light sensitive cells in the retina. We propose to use these models to gain a detailed understanding of the process of retinal degeneration and to follow this with an assessment of potential treatment options that will include the testing of various drugs, growth factors and gene replacement therapy using viral vectors delivered to the eye. This will enable us to determine the treatment for patients and will provide the first step towards a clinical trial.