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Gianluca Tosini, Kenkichi Baba, Anamika Sengupta, Susana Contreras-Alcantara, Sharon Owino; Melatonin Signaling and Photoreceptors Aging. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4332.
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In the mammalian retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin in the eye is believed to be involved in the modulation of many important retinal functions. Previous studies have shown that the levels of circulating melatonin levels decrease with age and such a decrease may contribute to neuronal degeneration during aging. Our previous studies have also shown that the viability of photoreceptors and ganglion cells is reduced during aging in MT1-/- mice thus demonstrating that melatonin signaling is important for the survival of retinal neurons. In the present study, we investigated the effects of aging on photoreceptor physiology and the effects of MT1 receptors removal.
C3H-f+/+and C3H-f+/+MT1-/- were used in this study. Photoreceptor function was assessed by electroretinography (ERG) and melatonin receptor level was measured by Real Time Quantitative RT-PCR and immunohistochemistry.
Our data indicate that the amplitude of the a- , b-wave of the dark-adapted ERGs decreases with age and that the daily rhythm of the ERGs is lost by the age of 12 months. Similarly the Scotopic Threshold Response (STR) is significantly affected by aging. Removal of the MT1 receptors accelerates the reduction in the amplitude of the a- and b-wave and increases the STR. Finally, we observed that administration of exogenous melatonin does not affect the ERGs in C3H-f+/+ at 12 months of age and the lack of response to administration of exogenous melatonin is due to the down-regulation of the MT1 receptors expression in the photoreceptors.
Our work indicates that melatonin and MT1 receptors play an important role in the modulation of retinal functions and removal of this receptor accelerated aging of the photoreceptors viability and function. Our data also show that melatonin receptors are greatly affected by aging and therefore harmacological treatments based upon melatonin administration may not be effective due to lack or reduced sensitivity of its receptors.
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