{Reference Type}: Journal Article
{Title}: The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.
{Author}: Das S;Chen Y;Yan J;Christensen G;Belhadj S;Tolone A;Paquet-Durand F;
{Journal}: Pflugers Arch
{Volume}: 473
{Issue}: 9
{Year}: 09 2021
{Factor}: 4.458
{DOI}: 10.1007/s00424-021-02556-9
{Abstract}: The second messengers, cGMP and Ca2+, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor cell death. This problem is exacerbated by the close connections and crosstalk between cGMP-signalling and calcium (Ca2+)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca2+-signalling relevant for hereditary photoreceptor degeneration. The topics covered include cGMP-signalling targets, the role of Ca2+ permeable channels, relation to energy metabolism, calpain-type proteases, and how the related metabolic processes may trigger and execute photoreceptor cell death. A focus is then put on cGMP-dependent mechanisms and how exceedingly high photoreceptor cGMP levels set in motion cascades of Ca2+-dependent and independent processes that eventually bring about photoreceptor cell death. Finally, an outlook is given into mutation-independent therapeutic approaches that exploit specific features of cGMP-signalling. Such approaches might be combined with suitable drug delivery systems for translation into clinical applications.