Unlike humans, teleosts like zebrafish exhibit robust retinal regeneration after injury from endogenous stem cells. However, it is unclear if regenerating cone photoreceptors regain physiological function and integrate correctly into post-synaptic circuits. We used two-photon calcium imaging of living adult retina to examine photoreceptor responses before and after light-induced lesions. To assess functional recovery of cones and downstream outer retinal circuits, we exploited color opponency; UV cones exhibit intrinsic Off-response to blue light, but On-response to green light, which depends on feedback signals from outer retinal circuits. Accordingly, we assessed the presence and quality of Off- vs. On-responses and found that regenerated UV cones regain both Off-responses to short-wavelength and On-responses to long-wavelength light within 3 months after lesion. Therefore, physiological circuit functionality is restored in regenerated cone photoreceptors, suggesting that inducing endogenous regeneration is a promising strategy for human retinal repair.

与人类不同，斑马鱼等硬骨鱼在内源性干细胞损伤后表现出强大的视网膜再生能力。然而，目前尚不清楚再生的视锥细胞是否能恢复生理功能并正确整合到突触后回路中。我们使用活体视网膜的双光子钙成像来检查光诱导损伤前后的光感受器反应。为了评估视锥细胞和下游外视网膜回路的功能恢复，我们利用了颜色对抗；紫外线视锥细胞对蓝光表现出固有的关闭响应，但对绿光表现出开启响应，这取决于来自外部视网膜电路的反馈信号。因此，我们评估了关闭响应与开启响应的存在和质量，发现再生的紫外线视锥细胞在损伤后 3 个月内恢复了对短波长光的关闭响应和对长波长光的开启响应。因此，再生的视锥细胞光感受器的生理回路功能得到恢复，这表明诱导内源性再生是人类视网膜修复的一种有前途的策略。