Sphingolipids as emerging mediators in retina degeneration

SIMON M.V.; PRADO SPALM F.H.; VERA M; ROTSTEIN N.P.

Frontiers in Cellular Neuroscience

Frontiers

Lugar: Lausana; Año: 2019

The sphingolipids ceramide (Cer), sphingosine-1-phosphate (S1P), sphingosine (Sph),and ceramide-1-phosphate (C1P) are key signaling molecules that regulate majorcellular functions. Their roles in the retina have gained increasing attention duringthe last decade since they emerge as mediators of proliferation, survival, migration,neovascularization, inflammation and death in retina cells. As exacerbation of theseprocesses is central to retina degenerative diseases, they appear as crucial players intheir progression. This review analyzes the functions of these sphingolipids in retinacell types and their possible pathological roles. Cer appears as a key arbitrator indiverse retinal pathologies; it promotes inflammation in endothelial and retina pigmentepithelium (RPE) cells and its increase is a common feature in photoreceptor deathin vitro and in animal models of retina degeneration; noteworthy, inhibiting Cer synthesispreserves photoreceptor viability and functionality. In turn, S1P acts as a double edgesword in the retina. It is essential for retina development, promoting the survivalof photoreceptors and ganglion cells and regulating proliferation and differentiationof photoreceptor progenitors. However, S1P has also deleterious effects, stimulatingmigration of Müller glial cells, angiogenesis and fibrosis, contributing to the inflammatoryscenario of proliferative retinopathies and age related macular degeneration (AMD). C1P,as S1P, promotes photoreceptor survival and differentiation. Collectively, the expandingrole for these sphingolipids in the regulation of critical processes in retina cell types andin their dysregulation in retina degenerations makes them attractive targets for treatingthese diseases.