Sphingosine Kinase-1 Is Essential for Maintaining External/Outer Limiting Membrane and Associated Adherens Junctions in the Aging Retina

Joseph L. Wilkerson, Megan A. Stiles, Jami M. Gurley, Richard C. Grambergs, Xiaowu Gu, Michael H. Elliott, Richard L. Proia, Nawajes Mandal

Research output: Contribution to journalArticle

Abstract

Sphingosine-1-phosphate (S1P) produced by sphingosine kinases (SPHK1 and SPHK2) is a signaling molecule involved in cell proliferation and formation of cellular junctions. In this study, we characterized the retinas of Sphk1 knockout (KO) mice by electron microscopy and immunocytochemistry. We also tested cultured Müller glia for their response to S1P. We found that S1P plays an important role in retinal and retinal pigment epithelial (RPE) structural integrity in aging mice. Ultrastructural analysis of Sphk1 KO mouse retinas aged to 15 months or raised with moderate light stress revealed a degenerated outer limiting membrane (OLM). This membrane is formed by adherens junctions between neighboring Müller glia and photoreceptor cells. We also show that Sphk1 KO mice have reduced retinal function in mice raised with moderate light stress. In vitro assays revealed that exogenous S1P modulated cytoskeletal rearrangement and increased N-cadherin production in human Müller glia cells. Aged mice also had morphological degeneration of the RPE, as well as increased lipid storage vacuoles and undigested phagosomes reminiscent of RPE in age-related macular degeneration. These findings show that SPHK1 and S1P play a vital role in the structural maintenance of the mammalian retina and retinal pigmented epithelium by supporting the formation of adherens junctions.

Original languageEnglish (US)
JournalMolecular Neurobiology
DOIs
StatePublished - Jan 1 2019

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Adherens Junctions
Retina
Retinal Pigments
Membranes
Knockout Mice
Neuroglia
Light
Phagosomes
Photoreceptor Cells
Macular Degeneration
Cadherins
Vacuoles
Electron Microscopy
Epithelium
Immunohistochemistry
Maintenance
Cell Proliferation
sphingosine 1-phosphate
sphingosine kinase
Lipids

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Sphingosine Kinase-1 Is Essential for Maintaining External/Outer Limiting Membrane and Associated Adherens Junctions in the Aging Retina. / Wilkerson, Joseph L.; Stiles, Megan A.; Gurley, Jami M.; Grambergs, Richard C.; Gu, Xiaowu; Elliott, Michael H.; Proia, Richard L.; Mandal, Nawajes.

In: Molecular Neurobiology, 01.01.2019.

Research output: Contribution to journalArticle

Wilkerson, Joseph L. ; Stiles, Megan A. ; Gurley, Jami M. ; Grambergs, Richard C. ; Gu, Xiaowu ; Elliott, Michael H. ; Proia, Richard L. ; Mandal, Nawajes. / Sphingosine Kinase-1 Is Essential for Maintaining External/Outer Limiting Membrane and Associated Adherens Junctions in the Aging Retina. In: Molecular Neurobiology. 2019.
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