Abed Sadaf, Reilly Andreea, Arnold Sebastian J, Feldheim David A
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, United States.
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Front Cell Neurosci. 2022 Mar 23;16:826590. doi: 10.3389/fncel.2022.826590. eCollection 2022.
Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs). ipRGCs regulate subconscious non-image-forming behaviors such as circadian rhythms, pupil dilation, and light-mediated mood. Previously, we and others showed that the transcription factor Tbr2 (EOMES) is required during retinal development for the formation of ipRGCs. Tbr2 is also expressed in the adult retina leading to the hypothesis that it plays a role in adult ipRGC function. To test this, we removed in adult mice. We found that this results in the loss of melanopsin expression in ipRGCs but does not lead to cell death or morphological changes to their dendritic or axonal termination patterns. Additionally, we found ectopic expression of Tbr2 in conventional RGCs does not induce melanopsin expression but can increase melanopsin expression in existing ipRGCs. An interesting feature of ipRGCs is their superior survival relative to conventional RGCs after an optic nerve injury. We find that loss of Tbr2 decreases the survival rate of ipRGCs after optic nerve damage suggesting that plays a role in ipRGC survival after injury. Lastly, we show that the GABAergic amacrine cell marker Meis2, is expressed in the majority of Tbr2-expressing displaced amacrine cells as well as in a subset of Tbr2-expressing RGCs. These findings demonstrate that is necessary but not sufficient for melanopsin expression, that is involved in ipRGC survival after optic nerve injury, and identify a marker for Tbr2-expressing displaced amacrine cells.
表达光色素黑视蛋白的视网膜神经节细胞具有内在光敏性（ipRGCs）。ipRGCs调节潜意识的非成像行为，如昼夜节律、瞳孔扩张和光介导的情绪。此前，我们和其他人表明，转录因子Tbr2（EOMES）在视网膜发育过程中是ipRGCs形成所必需的。Tbr2在成年视网膜中也有表达，这导致了一种假设，即它在成年ipRGC功能中发挥作用。为了验证这一点，我们在成年小鼠中去除了 。我们发现，这导致ipRGCs中黑视蛋白表达丧失，但不会导致细胞死亡或其树突或轴突终末模式的形态变化。此外，我们发现Tbr2在传统RGCs中的异位表达不会诱导黑视蛋白表达，但可以增加现有ipRGCs中的黑视蛋白表达。ipRGCs的一个有趣特征是，在视神经损伤后，它们相对于传统RGCs具有更高的存活率。我们发现，Tbr2的缺失会降低视神经损伤后ipRGCs的存活率，这表明 在损伤后ipRGCs的存活中发挥作用。最后，我们表明，GABA能无长突细胞标志物Meis2在大多数表达Tbr2的移位无长突细胞以及一部分表达Tbr2的RGCs中表达。这些发现表明， 对于黑视蛋白表达是必要的，但不是充分的， 参与视神经损伤后ipRGCs的存活，并确定了表达Tbr2的移位无长突细胞的标志物。
