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Shi-Jun Weng, Wen-Long Sheng, Xue Gong, Xiong-Li Yang, Yong-Mei Zhong; Modulatory Effects of Melatonin on Intrinsically Photosensitive Retinal Ganglion Cells in the Rat. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4138.
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© ARVO (1962-2015); The Authors (2016-present)
The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are under circadian modulation, but the underlying mechanism is not clear. We sought to explore whether and how melatonin, a neurohormone involved in various retinal circadian events, exerts modulatory effects on rat ipRGCs.
Melanopsin-driven light responses (M-responses) of ipRGCs in whole-mount retina were isolated with a glutamatergic blocker cocktail, and recorded using a multi-electrode array (MEA). Melatonin was administered in vitro in bath solution (for testing acute effects) or in vivo by intravitreal injection (for testing long-term effects while avoiding run-down). MEA data were fitted with the Michaelis-Menten equation to plot Irradiance-Response (I-R) curves for determining response thresholds. Whole-retina melanopsin levels were assessed using quantitative Western blotting.
Short-term (< 0.5 hour) bath application of melatonin failed to alter M-responses significantly, indicating the absence of an acute modulation. However, when the time of melatonin exposure was elongated to 2+ hours, achieved by intravitreal melatonin injection, M-responses were significantly suppressed in a dose-dependent manner, suggesting a long-term modulation of melatonin on ipRGC activities. The effect of melatonin was completely abolished by luzindole, a melatonin receptor antagonist, suggesting that the observed melatonin-induced suppression is a specific effect derived from melatonin receptor activation. Such a suppression was, at least in part, due to a decline in photopigment levels. The evidence was two folds. First, whole-retina melanopsin levels were significantly down-regulated in melatonin-treated eyes, as revealed by quantitative Western blotting, which could be reversed by luzindole. Second, M-responses in melatonin-treated eyes exhibited a rightward-shifted I-R curve, with a significantly elevated mean threshold, as compared with those in vehicle-treated eyes.
Retinal melatonin modulates ipRGC photosensitivity by down-regulating melanopsin expression, which may contribute to the previously reported circadian fluctuation in ipRGC activities.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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