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Greg H Matlock, Shrestha Priyadarsini, Volha Malechka, GUOTAO DENG, Fangfang Qiu, Kelu Zhou, Elizabeth P Moran, Dimitrios Karamichos, Jian-Xing (Jay) Ma; PPARα in diabetic keratopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1016. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Previous clinical trials have demonstrated therapeutic effects of Peroxisome-Proliferator Activated Receptor-Alpha (PPARα) agonists in diabetic retinopathy (DR) and diabetic peripheral neuropathy. The aim of this study was to investigate the protective role of PPARα against diabetic corneal neuropathy and keratopathy.
Experiments were conducted using PPARα-/- and wild-type mice and streptozotocin (STZ)-induced diabetic rats and controls. Diabetic and non-diabetic rats were divided into fenofibrate-treated and un-treated groups. Immunohistochemistry (IHC) staining of neuronal tubulin was used to quantify corneal nerve fiber density. IHC was used to visualize PPARα protein in the cornea from human donors with and without diabetes. Western blot analysis and RT-PCR were used to quantify PPARα expression in stromal cells from human corneas with and without diabetes.
Western blotting and RT-PCR results indicated significantly decreased PPARα protein and RNA levels in corneas from donors with diabetes compared to non-diabetic corneas (N=3, type 1 and type 2 diabetes; P<0.05). IHC in corneal sections demonstrated decreased PPARα in the epithelial layer. STZ-induced diabetic rats showed decreased nerve fiber density in the cornea, compared to age-matched non-diabetic rats. Treatment of diabetic rats with PPARα agonist fenofibrate prevented reduction in corneal nerve fiber density. IHC studies demonstrated decreased densities of corneal nerve fibers in non-diabetic PPARα-/- mice at 18 weeks and 20 months of age relative to age-matched wild-type mice (WT N=7, PPARα-/- N=6; P<0.05). At 20 months of age, corneal epithelial lesions were increased in PPARα-/- mice relative age-matched wild-type mice.
PPARα plays an important role in maintaining the integrity of corneal nerve fiber. Diabetes-induced PPARα down-regulation in the cornea may contribute to nerve degeneration in the cornea. Further studies will address mechanism of ocular neuronal degeneration in PPARα-/-mice and diabetes.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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