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Role of lysophosphatidic acid in the retinal pigment epithelium and photoreceptors

Citation

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, Role of lysophosphatidic acid in the retinal pigment epithelium and photoreceptors, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1863, (7) pp. 750-761. ISSN 1388-1981 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 Elsevier B.V.

DOI: doi:10.1016/j.bbalip.2018.04.007

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 Details

Item Type:Refereed Article
Keywords:autotaxin, human pluripotent stem cell, lysophosphatidic acid, optic cup, retinal pigment epithelium, tight junction
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:125848
Year Published:2018
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-05-09
Last Modified:2019-01-17
Downloads:0

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