Open Access

Ocular surface complications result from dysregulation of the OGF‑OGFr signaling pathway in female diabetic rats

  • Authors:
    • Indira Purushothaman
    • Ian S. Zagon
    • Joseph W. Sassani
    • Patricia J. Mclaughlin
  • View Affiliations

  • Published online on: April 28, 2021     https://doi.org/10.3892/etm.2021.10119
  • Article Number: 687
  • Copyright: © Purushothaman et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Approximately 4.5 million women in the United States exhibit diabetes‑associated ocular complications. The time course and magnitude of these complications, and their association with the dysregulation of the opioid growth factor (OGF)‑OGF receptor (OGFr) signaling pathway are unknown. The present study investigated the onset and magnitude of ocular surface complications and the association with a dysregulated OGF‑OGFr signaling pathway in diabetic female rats. Adult female Sprague‑Dawley rats were injected with streptozotocin in order to establish a model of type 1 diabetes (T1D), and a subset received insulin (T1D‑INS). Blood glucose, body weight, tear production and corneal sensitivity, as well as serum and tissue expression levels of OGF and OGFr, were assessed. Corneal epithelial wound healing was also evaluated. In a second study, female T1D rats were treated with topical naltrexone (NTX) to determine whether blockade of the OGF‑OGFr signaling pathway by NTX altered development of corneal surface complications. Female T1D rats had elevated glucose levels and reduced body weight compared with control and T1D‑INS rats. In both diabetic groups, tear production was decreased within 2 weeks and corneal sensitivity was decreased 2.5‑fold within 5 weeks, while corneal epithelial wound healing was delayed only in T1D rats. Serum and tissue levels of OGF and OGFr were elevated in diabetes. Twice daily NTX treatment reversed most ocular surface complications in the diabetic female rats. The present data demonstrated a seminal discovery in female T1D rats, in which the onset and magnitude of diabetes‑associated ocular surface complications were associated with dysregulation of the OGF‑OGFr regulatory pathway. Blockade of the OGF‑OGFr pathway with the opioid receptor antagonist NTX prevented the onset and/or decreased the magnitude of these deficits. The current data support the need for translational research on this therapeutic approach for diabetic human subjects.
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July-2021
Volume 22 Issue 1

Print ISSN: 1792-0981
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Spandidos Publications style
Purushothaman I, Zagon IS, Sassani JW and Mclaughlin PJ: Ocular surface complications result from dysregulation of the OGF‑OGFr signaling pathway in female diabetic rats. Exp Ther Med 22: 687, 2021.
APA
Purushothaman, I., Zagon, I.S., Sassani, J.W., & Mclaughlin, P.J. (2021). Ocular surface complications result from dysregulation of the OGF‑OGFr signaling pathway in female diabetic rats. Experimental and Therapeutic Medicine, 22, 687. https://doi.org/10.3892/etm.2021.10119
MLA
Purushothaman, I., Zagon, I. S., Sassani, J. W., Mclaughlin, P. J."Ocular surface complications result from dysregulation of the OGF‑OGFr signaling pathway in female diabetic rats". Experimental and Therapeutic Medicine 22.1 (2021): 687.
Chicago
Purushothaman, I., Zagon, I. S., Sassani, J. W., Mclaughlin, P. J."Ocular surface complications result from dysregulation of the OGF‑OGFr signaling pathway in female diabetic rats". Experimental and Therapeutic Medicine 22, no. 1 (2021): 687. https://doi.org/10.3892/etm.2021.10119