alexa Therapeutic Potential of Topical Fenofibrate Eyedrops i
ISSN: 2155-9570

Journal of Clinical & Experimental Ophthalmology
Open Access

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Research Article

Therapeutic Potential of Topical Fenofibrate Eyedrops in Diabetic Retinopathy and AMD Rat Models

Boyu Lu1,2, Yang Gao1,2, Wei Shen1, Qingjiong Zhang2, Yang Hu3* and Ying Chen1*
1Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
2Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
3Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
Corresponding Authors : Yang Hu, Ph.D.
825 N. E. 13th Street Oklahoma City, OK 73104; USA
Tel: (405) 271-2277
E-mail: [email protected]
  Ying Chen, M.D., Ph.D.
941 Stanton L. Young Blvd.
BSEB 31328B, Oklahoma City, OK 73104; USA
Tel: (405) 271-4629
Fax: (405) 271-3973
E-mail: [email protected]
Received April 11, 2014; Accepted July 07, 2014; Published July 14, 2014
Citation: Lu B, Gao Y, Shen W, Zhang Q, Hu Y, et al. (2014) Therapeutic Potential of Topical Fenofibrate Eyedrops in Diabetic Retinopathy and AMD Rat Models. J Clin Exp Ophthalmol 5:347. doi: 10.4172/2155-9570.1000347
Copyright: © 2014 Lu B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Objective: Diabetic retinopathy (DR) combined with age-related macular degeneration (AMD) is the leading cause of blindness in the US. Here, we report the efficacy of topical application of fenofibrate, an anti-lipid drug, in the treatment of retinal inflammation and neovascularization in rat models of DR and wet AMD, and in order to propose its use as a revolutionary therapy for ocular microvascular diseases.

Research design and methods: Fenofibrate was topically administered to rats. Following administration, the bioavailability of fenofibrate and its activated metabolite, fenofibric acid, in the retina, liver, and serum was determined using mass spectrometry. The effects of topical fenofibrate on retinal vascular leakage and inflammation were assessed using vascular permeability and leukostasis assays in streptozotocin (STZ)-induced diabetic rats. The anti-angiogenic effect of topical fenofibrate was evaluated in oxygen-induced retinopathy (OIR) rats and choroidal neovascularization (CNV) rats induced by laser photocoagulation.

Results: Treatment with topical fenofibrate caused no apparent corneal irritation or significant alterations in retinal histology in eyes. Fenofibrate rapidly distributed to the retina when applied topically, and the peak level of fenofibric acid in the retina occurred at 6 hours after administration. The terminal half-life of fenofibric acid in the retina was nearly 12 hours. Fenofibrate or fenofibric acid was not detected in the serum or liver by topical application, whereas oral administration of fenofibrate showed that the concentration of fenofibric acid in liver or serum was over 100-fold of that in the retina. Topical application of fenofibrate reduced the over-expression of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular endothelial growth factor (VEGF), attenuated retinal vascular leakage, and ameliorated inflammation in the experimental diabetic models and prevented retinal neovascularization in the OIR and CNV models.

Conclusion: Topical application of fenofibrate has therapeutic potential in preventing retinal and choroidal NV formation, amelioration retinal inflammation, and reduction of retinal NV leakage.

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