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Moon K. Kim, Moe H. Aung, Roy L. Sutliff, C. Michael Hart, Machelle T. Pardue; Disruption Of Endothelial Peroxisome Proliferator-activated Receptor Does Not Affect Electroretinography In Early Stages of STZ-induced Diabetes in Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5969.
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© ARVO (1962-2015); The Authors (2016-present)
While diabetic retinopathy (DR) is clinically diagnosed by vascular changes, there is increasing evidence of neuronal and glial changes. Here we examine the potential role of endothelial peroxisome proliferator-activated receptor γ (ePPARγ) in DR. PPARγ has been shown to decrease in early-stage DR and PPARγ agonists have been shown to have some protective effects on retinal vasculature. We hypothesized that eliminating PPARγ in endothelial cells of animals would accelerate diabetic retinal dysfunction.
Endothelial PPARγ null mice (ePPARγ KO) were created on pigmented C57 background using Cre-lox system while unaffected C57 mice (WT) served as controls. At approximately postnatal 180 days of age, diabetes was induced in randomly selected mice with streptozotocin (STZ; 50 mg/kg, IP), which yielded two additional treatment groups: ePPARγ KO-STZ and WT-STZ. Hyperglycemia was confirmed with blood glucose levels above 300 mg/dl. At 8 weeks post-diabetes, retinal function was assessed using scotopic electroretinography (ERG) with increasing flash intensities (3.9x10-4 to 768 cd s/m2). Amplitudes and implicit times of a- and b-waves, and oscillatory potentials (OPs) were measured for analysis.
No changes in a- and b-wave amplitudes and implicit times were observed in ePPARγ KO mice compared to other treatment groups (p>0.541, Two Way RM ANOVA). When analyzed for rod-driven inner retinal function, there were no differences in summed OP implicit times in ePPARγ KO compared to WT animals (p=0.424). The addition of hyperglycemia in the ePPARγ KO-STZ group did not produce significant retinal changes compared to ePPARγ KO and WT groups.
The absence of PPARγ in endothelial cells did not affect normal retinal function nor did it exacerbate the dysfunction seen in DR. These results would suggest that early changes in retinal function may originate from other sources, and it does not rule out the possibility that PPARγ has an effect in later stages of the disease or in other cell compartments.
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