Updates on sphingolipids: Spotlight on retinopathy

Biomed Pharmacother. 2021 Nov:143:112197. doi: 10.1016/j.biopha.2021.112197. Epub 2021 Sep 21.

Abstract

The sphingolipids ceramide (Cer), ceramide-1-phosphate (C1P), sphingosine (Sph), and sphingosine-1-phosphate (S1P)) are key signaling molecules that regulate many patho-biological processes. During the last decade, they have gained increasing attention since they may participate in important and numerous retinal processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Cer for instance has emerged as a key mediator of inflammation and death of neuronal and retinal pigment epithelium cells in experimental models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. S1P may have opposite biological actions, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide 1- phosphate may also contribute to uveitis. Furthermore, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), have been shown to preserve neuronal viability and retinal function. Collectively, the expanding role for these sphingolipids in the modulation of vital processes in retina cell types and in their dysregulation in retinal degenerations makes them attractive therapeutic targets.

Keywords: Age-related macular degeneration; Ceramide; Ceramide-1-phosphate; Photoreceptor; Retinal pigment epithelium; Sphingosine; Sphingosine-1-phosphate.

Publication types

  • Review

MeSH terms

  • Animals
  • Ceramides / metabolism
  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Lysophospholipids / metabolism
  • Molecular Targeted Therapy
  • Photoreceptor Cells, Vertebrate / metabolism
  • Retina / drug effects
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Diseases / drug therapy
  • Retinal Diseases / metabolism*
  • Retinal Diseases / pathology
  • Retinal Ganglion Cells / metabolism
  • Retinal Pigment Epithelium / metabolism
  • Signal Transduction
  • Sphingolipids / metabolism*
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism
  • Sphingosine 1 Phosphate Receptor Modulators / therapeutic use
  • Sphingosine-1-Phosphate Receptors / drug effects
  • Sphingosine-1-Phosphate Receptors / metabolism

Substances

  • Ceramides
  • Lysophospholipids
  • Sphingolipids
  • Sphingosine 1 Phosphate Receptor Modulators
  • Sphingosine-1-Phosphate Receptors
  • ceramide 1-phosphate
  • sphingosine 1-phosphate
  • Fingolimod Hydrochloride
  • Sphingosine