Transcriptomic profiling in 3-month-old P23H Retinitis Pigmentosa mouse retinas

Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cell dendrites expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed these issues in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network reminiscent of the neurodevelopmental state as well as potentiation of rod – rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. The results implicate retinal adaptation leading to persistent visual function during photoreceptor degenerative disease. Bulk retina mRNA profiling in heterozygous P23H rhodopsin mutated mice (n=4) and their wild-type littermates (n=3) at postnatal day 90针对光感受器变性（photoreceptor degeneration）的情况，已有研究观察到视网膜内层存在神经元可塑性（neuronal plasticity）。此前该现象通常被认为是适应不良的，或会阻碍盲人群体的视力恢复。不过，近期多项采用触发式光感受器消融技术的研究发现，双极细胞树突（bipolar cell dendrites）出现了适应性反应，这类反应本应支持正常视觉功能。但目前尚不清楚，在进行性光感受器变性疾病中，是否存在此类稳态可塑性（homeostatic plasticity）以帮助维持正常视觉行为。本研究在一种已成熟的色素性视网膜炎（Retinitis Pigmentosa）小鼠模型中探究了上述问题，该模型由视紫红质（rhodopsin）P23H突变诱发。研究结果显示，视杆光感受器变性后，视网膜转录组网络（transcriptomic network）出现显著重塑，其特征与神经发育状态相似，同时视杆-视杆双极细胞信号传导亦得到增强。此外，即便超过半数的视杆光感受器已丢失，P23H小鼠仍表现出高度敏感的夜间视觉能力。上述结果表明，视网膜的适应性重塑可在光感受器变性疾病进程中维持持续的视觉功能。本研究对出生后第90天的杂合子视紫红质P23H突变小鼠（n=4）及其野生型同窝幼鼠（n=3）开展了批量视网膜mRNA谱分析（bulk retina mRNA profiling）。