ARC Centre of Excellence in Vision Science, The Australian National University, Canberra, ACT, Australia.
Exp Eye Res. 2009 Dec;89(6):1003-11. doi: 10.1016/j.exer.2009.08.009. Epub 2009 Sep 1.
This study tests the potential of light restriction to optimise retinal structure and function in adulthood, using the P23H-3 rhodopsin-mutant transgenic rat as a model. P23H-3 rats were reared in scotopic (5 lux) or mesopic (40-60 lux) cyclic (12 h/12 h light/dark) light. A further 2 groups were reared in one of these light conditions to P(postnatal day)30, and then were transferred to the other condition. Retinae were examined at P30-365. Rod and cone function were assessed by the dark-adapted flash electroretinogram. The rate of photoreceptor death was assessed with the TUNEL technique, and photoreceptor survival by the thickness of the outer nuclear layer (ONL). Photoreceptor structural changes were assessed by immunohistochemistry. Mesopic rearing severely reduced the number, function and outer segment (OS) length of photoreceptors. Light restriction in the adult (achieved by moving mesopic-reared animals to scotopic conditions at P30) slowed photoreceptor death, induced recovery of the ERG and of OS length in survivors, resulting in an adult retina that matched the scotopic-reared in function, photoreceptor survival (stability) and structure. Conversely, light exposure in the adult (achieved by moving scotopic-reared animals to mesopic conditions at P30) accelerated photoreceptor death, shortened OSs and reduced the ERG, resulting in a retina that was as damaged and dysfunctional as a mesopic-reared retina, and showed greater photoreceptor instability. Present observations suggest, that the stability and function of adult photoreceptors are determined by both early and adult ambient light experience. Light restriction in the adult was effective in inducing the self-repair of photoreceptors, and the recovery of their function and stability. Light restriction in the juvenile (before P30) improved early photoreceptor survival but made adult photoreceptors vulnerable to brighter light experienced in adulthood. For comparable human dystrophies, these results suggest that light restriction begun after retinal maturation may be effective in optimising the structure, function and stability of the adult retina.
本研究以 P23H-3 视紫红质突变转基因大鼠为模型，测试光限制优化成年视网膜结构和功能的潜力。P23H-3 大鼠在暗（5lux）或中间（40-60lux）循环（12h/12h 明暗）光下饲养。另外两组在这些光照条件下饲养至 P(postnatal day)30，然后转移到另一种条件下。在 P30-365 时检查视网膜。通过暗适应闪光视网膜电图评估视杆和视锥功能。用 TUNEL 技术评估光感受器死亡率，用外核层（ONL）厚度评估光感受器存活率。用光感受器免疫组织化学评估光感受器结构变化。中间光照饲养严重减少了光感受器的数量、功能和外节（OS）长度。成年期的限光（通过将中间光照饲养的动物在 P30 时转移到暗光照条件下实现）减缓了光感受器的死亡，诱导了存活者的 ERG 和 OS 长度的恢复，从而使成年视网膜在功能、光感受器存活率（稳定性）和结构上与暗光照饲养的相似。相反，成年期的光照暴露（通过将暗光照饲养的动物在 P30 时转移到中间光照条件下实现）加速了光感受器的死亡，缩短了 OS 并降低了 ERG，导致视网膜与中间光照饲养的视网膜一样受损和功能障碍，并且表现出更高的光感受器不稳定性。目前的观察结果表明，成年光感受器的稳定性和功能由早期和成年环境光经验决定。成年期的限光在诱导光感受器的自我修复以及恢复其功能和稳定性方面是有效的。幼年（P30 之前）的限光改善了早期光感受器的存活率，但使成年光感受器容易受到成年期经历的更亮光线的影响。对于类似的人类营养不良，这些结果表明，在视网膜成熟后开始的限光可能有效优化成年视网膜的结构、功能和稳定性。
