Jain Varsha, Srivastava Ipsit, Palchaudhuri Shriya, Goel Manvi, Sinha-Mahapatra Sumit K, Dhingra Narender K
National Brain Research Centre, Manesar (Gurgaon), Haryana, India 122051.
PLoS One. 2016 Jun 13;11(6):e0157226. doi: 10.1371/journal.pone.0157226. eCollection 2016.
Pupillary light reflex (PLR) is an important clinical tool to assess the integrity of visual pathways. The available evidence suggests that melanopsin-expressing retinal ganglion cells (mRGCs) mediate PLR-driven by the classical photoreceptors (rods and cones) at low irradiances and by melanopsin activation at high irradiances. However, genetic or pharmacological elimination of melanopsin does not completely abolish PLR at high irradiances, raising the possibility that classical photoreceptors may have a role even at high irradiances. Using an inducible mouse model of photoreceptor degeneration, we asked whether classical photoreceptors are responsible for PLR at all irradiances, and found that the PLR was severely attenuated at all irradiances. Using multiple approaches, we show that the residual PLR at high irradiances in this mouse was primarily from the remnant rods and cones, with a minor contribution from melanopsin activation. In contrast, in rd1 mouse where classical photoreceptor degeneration occurs during development, the PLR was absent at low irradiances but intact at high irradiances, as reported previously. Since mRGCs receive inputs from classical photoreceptors, we also asked whether developmental loss of classical photoreceptors as in rd1 mouse leads to compensatory takeover of the high-irradiance PLR by mRGCs. Specifically, we looked at a distinct subpopulation of mRGCs that express Brn3b transcription factor, which has been shown to mediate PLR. We found that rd1 mouse had a significantly higher proportion of Brn3b-expressing M1 type of mRGCs than in the inducible model. Interestingly, inducing classical photoreceptor degeneration during development also resulted in a higher proportion of Brn3b-expressing M1 cells and partially rescued PLR at high irradiances. These results suggest that classical photoreceptors are primarily responsible for PLR at all irradiances, while melanopsin activation makes a minor contribution at very high irradiances.
瞳孔对光反射（PLR）是评估视觉通路完整性的一项重要临床工具。现有证据表明，表达黑视蛋白的视网膜神经节细胞（mRGCs）在低光照强度下介导由经典光感受器（视杆细胞和视锥细胞）驱动的PLR，而在高光照强度下则由黑视蛋白激活介导。然而，黑视蛋白的基因或药理学消除并不会在高光照强度下完全消除PLR，这增加了经典光感受器即使在高光照强度下也可能发挥作用的可能性。利用一种光感受器变性的诱导性小鼠模型，我们探究了经典光感受器在所有光照强度下是否都对PLR负责，并发现PLR在所有光照强度下均严重减弱。通过多种方法，我们表明该小鼠在高光照强度下的残余PLR主要来自残余的视杆细胞和视锥细胞，黑视蛋白激活的贡献较小。相比之下，如之前报道的，在发育过程中发生经典光感受器变性的rd1小鼠中，PLR在低光照强度下不存在，但在高光照强度下完整。由于mRGCs接收来自经典光感受器的输入，我们还探究了如rd1小鼠中经典光感受器的发育性缺失是否会导致mRGCs对高光照强度PLR的代偿性接管。具体而言，我们研究了表达Brn3b转录因子的mRGCs的一个独特亚群，该转录因子已被证明可介导PLR。我们发现，rd1小鼠中表达Brn3b的M1型mRGCs的比例显著高于诱导性模型。有趣的是，在发育过程中诱导经典光感受器变性也导致表达Brn3b的M1细胞比例更高，并在高光照强度下部分挽救了PLR。这些结果表明，经典光感受器在所有光照强度下主要负责PLR，而黑视蛋白激活在非常高的光照强度下贡献较小。
