Adult Expression of Tbr2 Is Required for the Maintenance but Not Survival of Intrinsically Photosensitive Retinal Ganglion Cells

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 Tbr2 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 Tbr2 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 Tbr2 is necessary but not sufficient for melanopsin expression, that Tbr2 is involved in ipRGC survival after optic nerve injury, and identify a marker for Tbr2-expressing displaced amacrine cells.

Automated summary

Retinal ganglion cells expressing the photopigment melanopsin, known as ipRGCs, are intrinsically photosensitive and play a role in regulating non-image-forming behaviors. The transcription factor Tbr2 is necessary for the formation of ipRGCs during retinal development, and its removal in adult mice leads to the loss of melanopsin expression. However, it does not result in cell death or morphological changes. Tbr2 is also involved in the survival of ipRGCs after optic nerve injury. Additionally, the GABAergic amacrine cell marker Meis2 is expressed in Tbr2-expressing displaced amacrine cells and a subset of Tbr2-expressing RGCs. These findings highlight the importance of Tbr2 in ipRGC function and survival, and provide a marker for Tbr2-expressing displaced amacrine cells.