Melatonin Signaling in Photoreceptors

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Melatonin is an important player in the regulation of many physiological functions within the body and within the retina. Several studies have shown that melatonin synthesis in the retina primarily occurs during the night and its levels are low during the day. Melatonin exerts its influence by binding to G protein-coupled receptors named melatonin receptor type 1 (MT1) and type 2 (MT2). MT1 and MT2 receptors activate a wide variety of signaling pathways and both receptors are present in the vertebrate photoreceptors where they may form MT1/MT2 heteromers (MT1/2h). Previous studies have also demonstrated that melatonin may play an important role in protecting photoreceptors from oxidative stress and can protect photoreceptors from apoptosis. Critically, melatonin signaling is involved in the modulation of photoreceptor functioning and viability during aging. Finally, new experimental evidence indicates that high fat diet (HFD) leads to a significant decrease in the amplitude of a- and b-wave of the scotopic ERGs in mice lacking MT1 signaling. The goal of this application is to elucidate the role of melatonin signaling plays in in the modulation of photoreceptor functioning and to determine if melatonin may represent a useful tool in the fight against retinal disorders. The present application comprises two specific aims. In specific aim 1 we will produce a rod specific MT1 knock out mice in a melatonin proficient genetic background. In specific aim 2 we will investigate the mechanism(s) by which MT1/2h signaling protects photoreceptor cells HFD. In our research, we will use a wide array of new and technologically advanced techniques as well as we will develop new lines of transgenic mice. Our proposal will provide important insights about the role of melatonin signaling in the modulation of photoreceptor health.