Potential therapeutic effects of peroxisome proliferator-activated receptors on corneal diseases

Abstract

The cornea is an avascular tissue in the eye that has multiple functions in the eye to maintain clear vision which can significantly impair one's vision when subjected to damage. Peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptor proteins comprising three different peroxisome proliferator-activated receptor (PPAR) isoforms, namely, PPAR alpha (α), PPAR gamma (γ), and PPAR delta (δ), have emerged as potential therapeutic targets for treating corneal diseases. In this review, we summarised the current literature on the therapeutic effects of PPAR agents on corneal diseases. We discussed the role of PPARs in the modulation of corneal wound healing, suppression of corneal inflammation, neovascularisation, fibrosis, stimulation of corneal nerve regeneration, and amelioration of dry eye by inhibiting oxidative stress within the cornea. We also discussed the underlying mechanisms of these therapeutic effects. Future clinical trials are warranted to further attest to the clinical therapeutic efficacy.

Keywords: cornea; fibrosis; inflammation; neovascularisation; nerve regeneration; proliferator-activated receptors; wound healing.

FIGURE 1

Representative corneal subbasal nerve images of healthy controls and type 2 diabetic patients before and after oral fenofibrate treatment. Corneal subbasal nerve of healthy controls (A, B). Corneal subbasal nerve before (C, D) and after (E, F) oral fenofibrate treatment, demonstrating an increase in nerve fiber density (9.25 ± 4.24 vs. 18.99 ± 8.49 n/mm²) and corneal nerve fiber width (0.0215 ± 0.0002 vs. 0.0224 ± 0.0005 µm²/mm²) after treatment.

FIGURE 2

Schematic diagram of the neuroprotective effects of PPARα agent, fenofibrate, in diabetic corneal neuropathy. ST6GAL1, Beta-galactoside alpha-2,6-sialytransferase 1; TTC9, Tetratricopeptide repeat protein 9A; RAB5A, ras-related protein; SMAD1, Suppressor of mothers against decapentaplegic homolog 1.

FIGURE 3

Illustration of the clinical applications of 3 PPAR isoforms in corneal diseases and its underlying mechanisms reported in the literature. Figure was created with BioRender.com.