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

34 Citations (Scopus)

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

Fingerprint

Corneal Epithelium
Diabetic Neuropathies
Streptozocin
Type 1 Diabetes Mellitus
Cell Count
Epithelial Cells
Corneal Diseases
Three-Dimensional Imaging
Nerve Fibers
Rodentia
Homeostasis
Maintenance
Pathology
Glucose
Growth
Serum

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium. / Cai, Daniel; Zhu, Meifang; Petroll, W. Matthew; Koppaka, Vindhya; Robertson, Danielle M.

In: American Journal of Pathology, Vol. 184, No. 10, 2014, p. 2662-2670.

Research output: Contribution to journalArticle

@article{e0805cb7d9a1438ea8b0c231c5239417,
title = "The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium",
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.",
author = "Daniel Cai and Meifang Zhu and Petroll, {W. Matthew} and Vindhya Koppaka and Robertson, {Danielle M.}",
year = "2014",
doi = "10.1016/j.ajpath.2014.06.016",
language = "English (US)",
volume = "184",
pages = "2662--2670",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - The impact of type 1 diabetes mellitus on corneal epithelial nerve morphology and the corneal epithelium

AU - Cai, Daniel

AU - Zhu, Meifang

AU - Petroll, W. Matthew

AU - Koppaka, Vindhya

AU - Robertson, Danielle M.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84922470446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922470446&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2014.06.016

DO - 10.1016/j.ajpath.2014.06.016

M3 - Article

C2 - 25102563

AN - SCOPUS:84922470446

VL - 184

SP - 2662

EP - 2670

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 10

ER -