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Role of lysophosphatidic acid in the retinal pigment epithelium and photoreceptors

Lidgerwood, GE, Morris, AJ, Conquest, A, Daniszewski, M, Rooney, LA, Lim, SY, Hernandez, D, Liang, HH, Allen, P, Connell, PP, Guymer, RH, Hewitt, AW ORCID: 0000-0002-5123-5999 and Pebay, A 2018 , 'Role of lysophosphatidic acid in the retinal pigment epithelium and photoreceptors' , Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, vol. 1863, no. 7 , pp. 750-761 , doi: 10.1016/j.bbalip.2018.04.007.

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Abstract

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.

Item Type: Article
Authors/Creators:Lidgerwood, GE and Morris, AJ and Conquest, A and Daniszewski, M and Rooney, LA and Lim, SY and Hernandez, D and Liang, HH and Allen, P and Connell, PP and Guymer, RH and Hewitt, AW and Pebay, A
Keywords: autotaxin, human pluripotent stem cell, lysophosphatidic acid, optic cup, retinal pigment epithelium, tight junction
Journal or Publication Title: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Publisher: Elsevier Science Bv
ISSN: 1388-1981
DOI / ID Number: 10.1016/j.bbalip.2018.04.007
Copyright Information:

Copyright 2018 Elsevier B.V.

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