Regulating survival and development in the retina: key roles for simple sphingolipids

N. ROTSTEIN; G. MIRANDA; C. ABRAHAN; GERMAN O L

JLR PAPERS IN PRESS

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2010 vol. 51 p. 1247 - 1266

0022-2275

Many sphingolipids have key functions in theregulation of crucial cellular processes. Ceramide (Cer) andsphingosine (Sph) induce growth arrest and cell death inmultiple situations of cellular stress. On the contrary, sphingosine-1-phosphate (S1P), the product of Sph phosphorylation,promotes proliferation, differentiation, and survival indifferent cell systems. This review summarizes the roles ofthese simple sphingolipids in different tissues and then analyzestheir possible functions in the retina. Alterations inproliferation, neovascularization, differentiation, and celldeath are critical in major retina diseases and collective evidencepoints to a role for sphingolipids in these processes.Cer induces infl ammation and apoptosis in endothelial andretinal pigmented epithelium cells, leading to several retinopathies.S1P can prevent this death but also promotes cellproliferation that might lead to neovascularization and fi -brosis. Recent data support Cer and Sph as crucial mediatorsin the induction of photoreceptor apoptosis in diversemodels of oxidative damage and neurodegeneration, andsuggest that regulating their metabolism can prevent thisdeath. New evidence proposes a central role for S1P controllingphotoreceptor survival and differentiation. Finally,this review discusses the ability of trophic factors toregulate sphingolipid metabolism and transactivate S1P signalingpathways to control survival and development in retinaphotoreceptors.