Sphingosine 1-phosphate, a potential target in neovascular retinal disease

cbn
Thumbnail Image
Files
Date
2021-05-07
Authors
Alshaikh, Rasha A.
Ryan, Katie B.
Waeber, Christian
Journal Title
Journal ISSN
Volume Title
Publisher
BMJ Publishing Group
Published Version
10.1136/bjophthalmol-2021-319115
Research Projects
Organizational Units
Journal Issue
Abstract
Neovascular ocular diseases (such as age-related macular degeneration, diabetic retinopathy and retinal vein occlusion) are characterised by common pathological processes that contribute to disease progression. These include angiogenesis, oedema, inflammation, cell death and fibrosis. Currently available therapies target the effects of vascular endothelial growth factor (VEGF), the main mediator of pathological angiogenesis. Unfortunately, VEGF blockers are expensive biological therapeutics that necessitate frequent intravitreal administration and are associated with multiple adverse effects. Thus, alternative treatment options associated with fewer side effects are required for disease management. This review introduces sphingosine 1-phosphate (S1P) as a potential pharmacological target for the treatment of neovascular ocular pathologies. S1P is a sphingolipid mediator that controls cellular growth, differentiation, survival and death. S1P actions are mediated by five G protein-coupled receptors (S1P1-5 receptors) which are abundantly expressed in all retinal and subretinal structures. The action of S1P on S1P1 receptors can reduce angiogenesis, increase endothelium integrity, reduce photoreceptor apoptosis and protect the retina against neurodegeneration. Conversely, S1P2 receptor signalling can increase neovascularisation, disrupt endothelial junctions, stimulate VEGF release, and induce retinal cell apoptosis and degeneration of neural retina. The aim of this review is to thoroughly discuss the role of S1P and its different receptor subtypes in angiogenesis, inflammation, apoptosis and fibrosis in order to determine which of these S1P-mediated processes may be targeted therapeutically.
Description
Keywords
Sphingosine-1 phosphate , Neovascularization , VEGF blockers , Angiogenesis , Age-related macular degeneration , Diabetic retinopathy , Retinal vein occlusion
Citation
Alshaikh, R. A., Ryan, K. B. and Waeber, C. (2021) 'Sphingosine 1-phosphate, a potential target in neovascular retinal disease', British Journal of Ophthalmology. doi: 10.1136/bjophthalmol-2021-319115
Link to publisher’s version
URI
https://hdl.handle.net/10468/11391
Collections
Pharmacy - Journal Articles
Pharmacology and Therapeutics - Journal Articles
Copyright
© 2021, the Authors. Published by BMJ Publishing Group Ltd. This article has been accepted for publication in British Journal of Ophthalmology following peer review, and the Version of Record can be accessed online at: http://dx.doi.org/10.1136/bjophthalmol-2021-319115 No commercial re-use.