Abstract | PURPOSE: METHODS: OIR was induced by exposing rat pups to alternating cycles of hyperoxia/ hypoxia from postnatal day (P) 0 to P14. RGC viability was evaluated by Fluorogold labeling. Effects of hyperoxia or hypoxia on LPA(1) expression were determined in the RGC-5 line by Western blot. Roles of hypoxia, LPA(1) receptor (with agonist, stearoyl-LPA; antagonist, THG1603; LPA(1) knock-down, shRNA-LPA(1)), and Rho kinase (with inhibitor Y-27632) in mediating RGC survival and neurite outgrowth were assessed by MTT assay and phase-contrast microscopy, respectively. Expression of GFP-LPA(1) in RGC-5 under hypoxia was examined by confocal microscopy. RESULTS: OIR caused pronounced RGC loss in the retina. LPA(1) receptor was expressed by RGCs in retinal tissue, whereas oxygen stress induced its expression in RGC-5. Exposure to stearoyl-LPA or hypoxia substantially reduced the viability of RGCs; this was abrogated by THG1603 and shRNA-LPA(1). THG1603 and Y-27632 treatment also attenuated the adverse effects of hypoxia on RGC-5 neurite outgrowth, and their intravitreal administration prevented OIR-induced RGC loss. Interestingly, overexpression of LPA(1) increased RGC-5 susceptibility to hypoxia-induced cell loss. CONCLUSIONS: Current data strongly support a critical role for LPA(1) receptor in mediating RGC degeneration during OIR.
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Authors | Chun Yang, Josiane Lafleur, Bupe R Mwaikambo, Tang Zhu, Carmen Gagnon, Sylvain Chemtob, Adriana Di Polo, Pierre Hardy |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 50
Issue 3
Pg. 1290-8
(Mar 2009)
ISSN: 1552-5783 [Electronic] United States |
PMID | 18978343
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amides
- Enzyme Inhibitors
- Pyridines
- Receptors, Lysophosphatidic Acid
- Y 27632
- Green Fluorescent Proteins
- rho-Associated Kinases
- Oxygen
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Topics |
- Amides
(pharmacology)
- Animals
- Animals, Newborn
- Blotting, Western
- Cell Culture Techniques
- Cell Survival
- Disease Models, Animal
- Enzyme Inhibitors
(pharmacology)
- Green Fluorescent Proteins
(genetics)
- Humans
- Hypoxia
(metabolism)
- Infant, Newborn
- Microscopy, Fluorescence
- Oxidative Stress
- Oxygen
(toxicity)
- Plasmids
(genetics)
- Pyridines
(pharmacology)
- Rats
- Rats, Long-Evans
- Receptors, Lysophosphatidic Acid
(physiology)
- Retinal Degeneration
(metabolism)
- Retinal Ganglion Cells
(metabolism, pathology)
- Retinopathy of Prematurity
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Transfection
- rho-Associated Kinases
(antagonists & inhibitors, physiology)
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