The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium

Daniel Cai, Meifang Zhu, W. Matthew Petroll, Vindhya Koppaka, Danielle M. Robertson

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis.

Original languageEnglish (US)
Pages (from-to)2662-2670
Number of pages9
JournalAmerican Journal of Pathology
Volume184
Issue number10
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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