Distribution of intracellular Ca2+-ATPases in the mouse retina and their involvement in light-induced cone degeneration

Abstract

Calcium signalling is involved in many processes in mammalian retina, from development to mature functions and neurodegeneration. Although proteins involved in Ca2+ entry in retinal cells have been well studied, less is known about Ca2+-clearance. Among the Ca2+ pumps, plasma membrane Ca2+-ATPases (PMCAs) have been identified as key proteins extruding Ca2+ across the plasma membrane with specific distribution in developing and adult retina. However, the two main isoforms of intracellular Ca2+-ATPases in the central nervous system, the sarco(endo)plasmic reticulum (ER) Ca2+-ATPase 2b (SERCA2b) and the secretory pathway Ca2+-ATPase 1 (SPCA1), which remove cytosolic Ca2+ into intracellular stores, have been less or not at all analysed, respectively. In this study, we described for the first time the SPCA1 localisation in adult mouse retina and we report differential distributions of SERCA2b and SPCA1 transporters within various classes of retinal neurons and distinct subcellular localisations. In addition, we studied the expression and localisation of both Ca2+ pumps in 661W cells, a cone photoreceptor-derived cell line. Since continuous exposure to high light intensity induces photodegeneration, we analysed the effect of LED light exposure on these cells and SERCA2b and SPCA1 distribution. We found that continuous mild LED-light exposure compromised cell survival and produced stress in the ER and Golgi, the Ca2+ stores where the two pumps are localised. These effects were reversed after halting light exposure and washing. This study demonstrates that Ca2+ signalling may be involved in light-induced photoreceptor cell damage and points to previously unrecognised functions of intracellular Ca2+-ATPases in retina physiology.