Insulin eye drops improve corneal wound healing in STZ-induced diabetic mice by regulating corneal inflammation and neuropeptide release

BMC Ophthalmol. 2024 Apr 9;24(1):155. doi: 10.1186/s12886-024-03436-3.

Abstract

Introduction: In recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds.

Methods: A type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1β, β3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury.

Results: Fluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining.

Conclusions: Our results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.

Keywords: Diabetic keratopathy; Inflammation; Insulin eye drops; Nerve regeneration; Neuropeptides.

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Cornea / physiology
  • Corneal Injuries* / drug therapy
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Epithelium, Corneal* / metabolism
  • Fluorescein / metabolism
  • Inflammation / metabolism
  • Insulin
  • Keratitis* / metabolism
  • Ki-67 Antigen / metabolism
  • Mice
  • Ophthalmic Solutions
  • Wound Healing

Substances

  • Insulin
  • Calcitonin Gene-Related Peptide
  • Ophthalmic Solutions
  • Ki-67 Antigen
  • Fluorescein