# OGF-OGFr Axis Modulation to Prevent Diabetic Ocular Surface Complications.

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $370,544

## Abstract

Project Summary
Diabetes is increasing globally and more than 9% of the US population has diabetes, with an additional 86 million
pre-diabetic adult Americans. Type 1 diabetes mellitus (T1D) affects nearly 1.5 million Americans, accounting for
almost $18 billion annually in healthcare costs. Diabetic-related complications such as retinopathy and
cardiovascular disease receive much public attention, and 3 corneal disorders including keratopathy, dry eye,
and surface insensitivity lead to vision loss, elevated healthcare costs, and decreased job productivity. This
application focuses on the Opioid Growth Factor (OGF) – Opioid Growth Factor Receptor (OGFr) regulatory
system and blockade by naltrexone (NTX) to prevent ocular surface complications arising from Type 1 diabetes
(T1D). Preventive intervention of diabetes-related complications remains an unmet medical need. The underlying
hypothesis in this proposal is that the OGF-OGFr axis becomes dysregulated during the development of diabetes
leading to over-expression of the inhibitory peptide and/or dysregulation of OGFr thus causing diabetes-
associated ocular surface complications. The proposed research will i) Determine the temporal course and
magnitude of defects in the OGF-OGFr regulatory pathway during the development of T1D in rats in order to
properly initiate preventive therapy, 2) Determine whether topical or systemic administration of NTX prevents or
delays the appearance of ocular surface complications. 3) Identify other molecular and protein biomarkers
related to diabetes such as delayed corneal wound healing, dry eye, and insensitivity, and determine whether
NTX intervention alters their expression and function. This knowledge will advance precision medicine
approaches for the prevention and treatment of diabetic complications. This application represents the
culmination of several decades of research determining that OGF-OGFr blockade with NTX is effective at
treating diabetic ocular surface complications, and for the first time, will determine the ability of such blockade by
NTX to prevent diabetic ocular surface complications. There is evidence that diabetes is accompanied by
dysregulation in expression of endogenous opioids (i.e., OGF) and their receptors leading to an elevated
expression of inhibitory growth factors. For more than 2 decades our laboratory has conducted research to
determine the role of this regulatory axis in contributing to diabetic complications in diabetic rat, mouse, and
rabbit and demonstrated that topical NTX reverses dry eye to normal tear production, accelerates delayed
corneal wound healing, and restores the diabetic complication of decreased corneal sensitivity to normal in these
diabetic animals. The proposed research will determine for the first time the ability of OGF-OGFr axis blockade
by NTX to prevent these complications. Our research team has clinical and basic science expertise in all aspects
of this research and will be able to rapidly translate...

## Key facts

- **NIH application ID:** 10203997
- **Project number:** 5R01EY029223-04
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** IAN S ZAGON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,544
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10203997

## Citation

> US National Institutes of Health, RePORTER application 10203997, OGF-OGFr Axis Modulation to Prevent Diabetic Ocular Surface Complications. (5R01EY029223-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10203997. Licensed CC0.

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