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Role of lysophosphatidic acid in the retinal pigment epithelium and photoreceptors

journal contribution
posted on 2023-05-19, 17:57 authored by Lidgerwood, GE, Morris, AJ, Conquest, A, Daniszewski, M, Rooney, LA, Lim, SY, Hernandez, D, Liang, HH, Allen, P, Connell, PP, Guymer, RH, Alexander HewittAlexander Hewitt, Pebay, A
The human retina is a complex structure of organised layers of specialised cells that support the transmission of light signals to the visual cortex. The outermost layer of the retina, the retinal pigment epithelium (RPE), forms part of the blood retina barrier and is implicated in many retinal diseases. Lysophosphatidic acid (LPA) is a bioactive lipid exerting pleiotropic effects in various cell types, during development, normal physiology and disease. Its producing enzyme, AUTOTAXIN (ATX), is highly expressed by the pigmented epithelia of the human eye, including the RPE. Using human pluripotent stem cell (hPSC)-derived retinal cells, we interrogated the role of LPA in the human RPE and photoreceptors. hPSC-derived RPE cells express and synthesize functional ATX, which is predominantly secreted apically of the RPE, suggesting it acts in a paracrine manner to regulate photoreceptor function. In RPE cells, LPA regulates tight junctions, in a receptor-dependent mechanism, with an increase in OCCLUDIN and ZONULA OCCLUDENS (ZO)-1 expression at the cell membrane, accompanied by an increase in the transepithelial resistance of the epithelium. High concentration of LPA decreases phagocytosis of photoreceptor outer segments by the RPE. In hPSC-derived photoreceptors, LPA induces morphological rearrangements by modulating the actin myosin cytoskeleton, as evidenced by Myosin Light Chain l membrane relocation. Collectively, our data suggests an important role of LPA in the integrity and functionality of the healthy retina and blood retina barrier.

History

Publication title

Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Volume

1863

Issue

7

Pagination

750-761

ISSN

1388-1981

Department/School

Menzies Institute for Medical Research

Publisher

Elsevier Science Bv

Place of publication

Po Box 211, Amsterdam, Netherlands, 1000 Ae

Rights statement

Copyright 2018 Elsevier B.V.

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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