In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa
In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa
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DOI：
10.1073/pnas.0408892102
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发表时间：
2005-04-05
影响因子：
11.1
通讯作者：
Aguirre, GD
中科院分区：
文献类型：
--
作者：
Cideciyan, AV;Jacobson, SG;Aguirre, GD
遗传和环境因素改变了人类神经退行性变的严重程度。由视紫红质基因突变引起的视网膜变性在家族内和家族之间，甚至在同一只眼睛的区域内显示出严重性差异。环境光被认为有助于这种变化。在人类疾病的自然发生的狗模型中，我们发现常规临床实践中使用的适度光照水平显着加速了神经变性。急性视网膜损伤（包括异常的视网膜内光散射）的动态在体内用高分辨率光学成像真实的时间可视化。长期后果包括快速或缓慢的视网膜变性或损伤修复，这取决于光暴露的剂量。这些实验为研究神经元损伤、修复、代偿和变性的机制提供了平台。这些数据还支持在人类视紫红质疾病中进行基因特异性光减少临床试验。
Genetic and environmental factors modify the severity of human neurodegenerations. Retinal degenerations caused by rhodopsin gene mutations show severity differences within and between families and even within regions of the same eye. Environmental light is thought to contribute to this variation. In the naturally occurring dog model of the human disorder, we found that modest light levels, as used in routine clinical practice, dramatically accelerated the neurodegeneration. Dynamics of acute retinal injury (consisting of abnormal intraretinal light scattering) were visualized in vivo in real time with high-resolution optical imaging. Long term consequences included fast or slow retinal degeneration or repair of injury depending on the dose of light exposure. These experiments provide a platform to study mechanisms of neuronal injury, repair, compensation, and degeneration. The data also argue for a gene-specific clinical trial of light reduction in human rhodopsin disease.