Abstract
Purpose :
Diabetic ocular surface complications (e.g., dry eye, altered surface sensitivity, or delayed corneal epithelial wound repair) can be reversed by topical application of naltrexone, an opioid receptor antagonist, thereby reflecting the role of the Opioid Growth Factor (OGF) – OGF receptor regulatory axis in this disease. We hypothesize that the course of dysregulation of the inhibitory peptide OGF coincides with the onset of these abnormalities.
Methods :
Male Sprague-Dawley rats were rendered hyperglycemic with streptozotocin (STZ) to produce type 1 diabetes (T1D). Some STZ-injected animals received insulin implants (T1D-INS); non-diabetic rats served as controls (Normal). Corneal surface sensitivity (Cochet-Bonnet aesthesiometer) and dry eye (Schirmer 1 test) were monitored weekly for 8 weeks, and the rates of healing for 5 mm corneal abrasions were calculated at week 5 after STZ induction. Blood was collected weekly to measure serum OGF levels by ELISA, and OGF expression in the corneal epithelium was measured by immunohistochemistry at week 6.
Results :
Within 72 hr of STZ injection, T1D blood glucose levels exceeded 500 mg/dL and body weights were significantly reduced, whereas T1D-INS rats had glucose levels (~130 mg/dL) and body weights comparable to Normals. Corneal sensitivity was altered in both T1D and T1D-INS beginning on week 4, requiring nearly a 2-fold increased pressure to elicit a blink response. Tear production was reduced in T1D and T1D-INS groups (~3.5 mm) relative to Normals (~6 mm) beginning at week 5 and continued through week 8. Rates of corneal epithelial wound closure were delayed by 14 hr in the T1D-INS group and by 34 hr in the T1D group relative to Normals. Serum OGF levels were significantly elevated at 4, 5, and 6 weeks for both the T1D and T1D-INS groups, and OGF expression in the corneal epithelium was elevated more than 2-fold in both T1D and T1D-INS groups relative to Normals at week 6.
Conclusions :
The data demonstrate that abnormal serum and tissue levels of the inhibitory peptide OGF coincide with ocular surface complications in T1D rats. In some cases, insulin provided partial protection against diabetic-related corneal complications. Studies to determine whether blockade of the OGF-OGFr pathway with naltrexone can prevent these complications need to be completed.
This is a 2020 ARVO Annual Meeting abstract.