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VS Rajaratnam, SE Kai, JS Penn; Expression of Peroxisome Proliferator Activated Receptors (PPAR) Alpha, Beta and Gamma and Their Angiostatic Effects in a Rat Model of Retinopathy of Prematurity . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3717.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To analyze the expression of PPARα, ß and γ in the developing rat retina; to verify if hypoxia inhibits expression of PPARs in the rat model of ROP; and, if PPARs are present in hypoxic retina, to determine their effects on neovascularization upon ligand treatment. Methods: Newborn albino rats were exposed to alternating 24 hr. periods of 50% and 10% oxygen for 14 days. Intravitreal injections were done immediately upon removal of the pups to room air (day 14/0). PPAR specific ligands, an endogenous PGJ215dΔ; 12,14 (0.2-100µM), a thiazolidinedione (TZD) Ciglitazone (5-20µM), a fibrate WY14643 (10µM-100µM) and a non steroid anti-inflammatory drug SSd (20µM-200µM) were used. For ADPase staining and scoring of retinal neovascularization (NV), retinas were dissected and flat mounted on day 14/6. Retinas from room air raised (P5-P20) and oxygen exposed pups [14/1 (P15) and 14/3 (P18)] were flash frozen for protein and RNA extraction. Expression levels of PPARs were analyzed by western analysis and RNAse protection assay (RPA). Results: Levels of expression of PPARs change in the developing retina with age and receptor type. There was no significant difference in PPAR expression levels between room air and oxygen treated retinas of same age as detected by RPA or western, except for PPARß. Upon treatment with PPAR ligands, retinal NV was inhibited 25-80%, compared to vehicle treated eyes. The effectiveness depended on the ligand and concentration used. Among the PPAR ligands, PGJ215dΔ;12,14 and SSd were found to be the most potent and very effective at 2-5µM (P<0.003) and 200µm (P<0.001), respectively. Conclusion: PPARs are expressed in the neonate rat retina and none of the PPAR receptors were significantly inhibited by hypoxia. Treatments with ligands indicate that PPARs in hypoxic retina can be targeted to effectively inhibit retinal NV. Thus, these receptors have great potential as therapeutic targets for ROP and other angiogenic ocular conditions.
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