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Xiaoyan Zhang, Yi-qin Xiao, Yu Zhang, Jiaying zhang, Wen Ye; Protective effects of an PPAR-γ agonist on retinal ischemia/reperfusion injury in rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6316.
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To investigate the protective effects of an PPAR-γ agonist in the rat retina after ischemia/reperfusion (I/R) injury.
Retinal ischemia was induced in rats by increasing the intraocular pressure to 110mmHg for 60 minutes. The PPAR-γ agonist was delivered by periocular injection and intraperitoneal injection before I/R. Seven days after I/R injury, retinal damage was quantified by measuring the thickness of the retina, the functional changes of VEP and ERG, and the RGC number. The expression of GFAP, NF-κB p65 in the retina was determined by western blot, real-time polymerase chain reaction (PCR), and immunohistochemistry.
I/R caused severe disruption of the retinal construction and integrity. In I/R group without treatment the number of RGCs was reduced by 53%. The PPAR-γ agonist either delivered by periocular injection or by intraperitoneal injection preserved the thickness of the retina after I/R, and the survival of RGC was 77% and 74% respectively. Pretreated with the PPAR-γ agonist also attenuate the destruction of VEP and ERG caused by I/R. The amplitudes of the ERG b-waves and the VEP P1-N2 component were significantly lower in the I/R group than in the groups pretreated with the PPAR-γ agonist (p<0.01). After ischemia, expression of GFAP, NF-κB p65 subunit was upregulated and high phosphoration level of p65 subunit was detected in retina. The PPAR-γ agonist pretreatment suppressed NF-κB activation and reduced the GFAP overexpression.
The PPAR-γ agonist promotes the survival of RGCs and protect retina histological integrity as well as retinal function after retinal I/R. The protect effect appears to act through the anti-inflammatory effects towards the inhibition of retinal glia activation, suggesting that the PPAR-γ agonist may have a therapeutic potential for the prevention of retinal diseases associated with I/R.
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