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Simon Pan, Samer Hattar, Tiffany M Schmidt; Role for intrinsically photosensitive retinal ganglion cells in modulating dopaminergic amacrine cell development. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5762.
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© ARVO (1962-2015); The Authors (2016-present)
A subset of retinal ganglion cells (RGCs) express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). A subtype of ipRGC, the M1 ipRGC, has been shown to costratify their dendrites with DAC processes in the OFF sublamina of the interplexiform layer. Additionally, ipRGCs have been demonstrated to signal to DACs in a retrograde manner. However, the effects of ipRGC inputs on DAC development and survival is unknown.
We performed whole mount immunohistochemistry in the mouse retina for tyrosine hydroxylase to identify the DAC population throughout development on several animal models where mice lack either ipRGCs or the melanopsin photopigment. Animals raised in either constant light or constant darkness were also examined.
We report a significant deficit in the total number of tyrosine hydroxylase (TH) positive DACs in mice whose ipRGCs have been genetically ablated by a diphtheria toxin (DTA) early in development. This deficit can be detected as early as P14 and persists into adulthood. Surprisingly, adult mice where ipRGCs are not ablated until adult stages via expression of an attenuated diphtheria toxin (aDTA) show a similar deficit to adult DTA animals, demonstrating that loss of ipRGCs at any developmental stage causes a loss of TH positive amacrine cells. Examination of the processes of DACs in DTA animals reveal that the morphology of the remaining cells was unaffected. Interestingly, rearing of WT animals in constant darkness did not affect the number of TH positive cells.
Our findings implicate ipRGCs in a novel role in regulating the total number of DACs in the retina. DAC loss by ipRGC ablation can be detected in early postnatal development but can also be induced in adult animals, suggesting possible involvement in both the development and maintenance of the DAC population.
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