A role of the anoctamin membrane protein family in the homeostasis of the retina

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Ion channels are essential to maintain multiple homeostatic processes in the retina. A detailed knowledge of their molecular identity is critically required to understand the specific functional role(s) of each ion channel in the normal retina and in the pathogenesis of retinal diseases. In recent work, we discovered that members (Ano2-4) of the newly discovered anoctamin ion channel family are expressed in photoreceptors, Müller cells and in cells of the retinal pigment epithelium (RPE).We hypothesize that Ano2-4 contribute to important homeostatic functions in the retina and plan to investigate their specific functional properties. To this end we will a.) investigate the basic ion channel properties of heterologously expressed anoctamins and analyse their functional interaction with other molecules b.) analyze endogenously expressed anoctamins and their involvement in Müller and RPE cell function. Although preliminary data and current literature strongly suggest ion channel function of the so far unexplored Ano3-4, we will explore alternative functions such as regulation of membrane conductance. In the course of these studies, we will characterize the basic functions of so far unexplored members of the anoctamin family, their functional relevance for the retina in health and their impact in retinal degeneration.