University of Michigan, Department of Ophthalmology and Visual Sciences, 1000 Wall St. Ann Arbor, MI, 48105, USA.
University of Michigan, Department of Ophthalmology and Visual Sciences, 1000 Wall St. Ann Arbor, MI, 48105, USA.
Exp Eye Res. 2022 Feb;215:108913. doi: 10.1016/j.exer.2021.108913. Epub 2021 Dec 26.
Inherited retinal diseases (IRDs) are a collection of rare genetic conditions, which can lead to complete blindness. A large number of causative genes have been identified for IRDs and while some success has been achieved with gene therapies, they are limited in scope to each individual gene and/or the specific mutation harbored by each patient with an IRD. Multiple studies are underway to elucidate common underlying mechanisms contributing to photoreceptor (PR) loss and to design gene-agnostic, pan-disease therapeutics. The rd10 mouse, which recapitulates slow degeneration of PRs, is an in vivo IRD model used commonly by vision researchers. Light deprivation by rearing animals in complete darkness significantly delays PR death in rd10 mice, subsequently increasing the time window for in vivo studies investigating neuroprotective strategies. Longitudinal in vivo retinal imaging following the same rd10 mice over time is a potential solution for reducing the number of animals required to complete a study. We describe a previously unreported phenotype in the dark-reared rd10 model that is characterized by dramatic PR degeneration following brief exposure to low-intensity light. This exquisite light sensitivity precludes the use of longitudinal studies employing in vivo imaging or other functional assessment requiring room light in rd10 mice and highlights the importance of closely following animal models of IRD to determine any deviations from the expected degeneration curve during routine experimentation.
遗传性视网膜疾病(IRDs)是一组罕见的遗传疾病,可导致完全失明。已经确定了大量导致 IRD 的致病基因,尽管基因疗法已经取得了一些成功,但它们的范围仅限于每个个体基因和/或每个患有 IRD 的患者所携带的特定突变。多项研究正在进行中,以阐明导致光感受器(PR)丧失的常见潜在机制,并设计针对基因的泛疾病治疗方法。rd10 小鼠重现了 PR 的缓慢退化,是视觉研究人员常用的体内 IRD 模型。通过将动物在完全黑暗中饲养来剥夺光照可显著延迟 rd10 小鼠中 PR 的死亡,从而增加了用于研究神经保护策略的体内研究的时间窗口。对同一只 rd10 小鼠进行长时间的纵向活体视网膜成像,是减少完成研究所需动物数量的一种潜在解决方案。我们描述了暗饲养 rd10 模型中以前未报道的表型,其特征是在短暂暴露于低强度光后出现明显的 PR 退化。这种高度的光敏感性排除了在 rd10 小鼠中使用纵向研究进行活体成像或其他需要室内光的功能评估的可能性,这突出了密切关注 IRD 动物模型的重要性,以确定在常规实验过程中是否存在与预期退化曲线的偏差。