Corneal Complications in Streptozocin-Induced Type I Diabetic Rats

Abstract

PURPOSE. This study seeks to characterize corneal functions and complications in a streptozocin (STZ)-induced rat model of type I diabetes mellitus (DM) and to understand the pathogenesis of diabetic keratopathy. METHODS. DM was induced via STZ injection in Sprague-Dawley rats. Body weight, length, and corneal size were measured and compared with the age-matched normal controls. Corneal morphology and histology were evaluated with slit lamp, digital confocal microscopy and hematoxylin and eosin staining. Tear secretion was measured with cotton threads, and corneal sensitivity was determined with an esthesiometer. Protein expression and distribution were assessed with Western blotting and immunohistochemistry. Wound healing was determined using an in vivo corneal epithelial debridement model. RESULTS. Compared with the normal control rats, STZ rats had reduced body weight, and body length, but minimally affected corneal size. No significant changes in ocular surface regularity, corneal thickness, and morphology were noted in diabetic corneas. STZ rats showed stronger Rose Bengal staining, decreased tear secretion, slightly attenuated sensitivity, less innervation, delayed epithelial wound healing, and impaired epidermal growth factor receptor signaling in their corneas. While the expression of adherens junction protein β-catenin, and tight junction proteins occludin and ZO-1 was unchanged, the formation of these junctions after wound closure was delayed. CONCLUSIONS. Pathogenesis of diabetic keratopathy involves multiple tissues and/or cell types and several events including reduced tear secretion, impaired innervation, weakened cell junction, and altered wound responses. These insights may prove useful for the clinical translation of evolving strategies for the management and treatment of diabetic corneal complications.

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

“…For nerve staining, an additional 2-day permeabilization was performed before incubation with TUJ1 antibody (2 mg/mL; Covance Research, Princeton, NJ). 27 The stained tissues were coverslipped with mounting medium (H1000; Vector Laboratories, Burlingame, CA) and examined under a confocal microscope (SP8; Leica). Images were analyzed by ImageJ version 1.48v (NIH, Bethesda, MD).…”

“…26,27 Herein, we determined the role of IL-1Ra in corneal sensory nerve regeneration A: Infiltrating neutrophils stained by NIMP-R14. B: Infiltrating NK (T) cells stained by NK1.1.…”

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

“…10 However, the attenuation of corneal innervations, caused by herpetic viral infection, trigeminal nerve damage, or diabetic mellitus, can cause impaired corneal sensation, chronic inflammation, delayed corneal epithelial wound healing, and even persistent defects. [18][19][20][21][22][23] Corneal neovascularization (CNV) is a major sight-threatening complication of various ocular injuries. In recent years, the topical application or subconjunctival injection of bevacizumab has been confirmed for CNV treatment in both animals and humans.…”

Ocular Surface Complications after Trabeculectomy: Incidence, Risk Factors, Time Course and Prognosis

“…An association between epithelial fragility, impaired corneal wound healing and diabetes mellitus has been reported in both humans and animals [25,26,27,28]. Chung et al [29] reported that diabetes mellitus is a risk factor for the occurrence of corneal complications after vitrectomy.…”