Topical and oral peroxisome proliferator-activated receptor-α agonist ameliorates diabetic corneal neuropathy

Hassan Mansoor, Isabelle Xin Yu Lee, Molly Tzu-Yu Lin, Heng Pei Ang, Yao Cong Xue, L. Krishaa, Moushmi Patil, Siew-Kwan Koh, Hong Chang Tan, Lei Zhou, Yu-Chi Liu (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Diabetic corneal neuropathy (DCN) is a common diabetic ocular complication with limited treatment options. In this study, we investigated the effects of topical and oral fenofibrate, a peroxisome proliferator-activated receptor-α agonist, on the amelioration of DCN using diabetic mice (n = 120). Ocular surface assessments, corneal nerve and cell imaging analysis, tear proteomics and its associated biological pathways, immuno-histochemistry and western blot on PPARα expression, were studied before and 12 weeks after treatment. At 12 weeks, PPARα expression markedly restored after topical and oral fenofibrate. Topical fenofibrate significantly improved corneal nerve fibre density (CNFD) and tortuosity coefficient. Likewise, oral fenofibrate significantly improved CNFD. Both topical and oral forms significantly improved corneal sensitivity. Additionally, topical and oral fenofibrate significantly alleviated diabetic keratopathy, with fenofibrate eye drops demonstrating earlier therapeutic effects. Both topical and oral fenofibrate significantly increased corneal β-III tubulin expression. Topical fenofibrate reduced neuroinflammation by significantly increasing the levels of nerve growth factor and substance P. It also significantly increased β-III-tubulin and reduced CDC42 mRNA expression in trigeminal ganglions. Proteomic analysis showed that neurotrophin signalling and anti-inflammation reactions were significantly up-regulated after fenofibrate treatment, whether applied topically or orally. This study concluded that both topical and oral fenofibrate ameliorate DCN, while topical fenofibrate significantly reduces neuroinflammation.
Original languageEnglish
Article number13435
Pages (from-to)1-14
Number of pages14
JournalScientific Reports
Volume14
DOIs
Publication statusPublished - 11 Jun 2024

Keywords

  • Corneal diseases
  • Translational research

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