Abstract
Purpose :
Diabetes affects males and females equally, and approximately 30% of the 15-16 million females with diabetes in the U.S. will have ocular complications such as dry eye, abnormal surface sensitivity, and delayed corneal epithelial repair. Topical naltrexone therapy has been shown to effectively reverse these complications in male rats with type 1 diabetes (T1D), but little information is known about ocular surface defects in female models. The aim of the present study was to determine whether the magnitude and temporal course of these corneal complications differed between T1D and T1D-INS female rats.
Methods :
Female adult Sprague-Dawley rats were made hyperglycemic with streptozotocin (STZ), a model of T1D, and a subset of STZ-injected rats were implanted with LinShin insulin minipumps (T1D-INS) to establish controlled hyperglycemia; non-diabetic rats received buffer only (=Normal). Body weights and blood glucose levels were measured weekly. Changes in corneal surface sensitivity (aesthesiometer) and dry eye (Schirmer 1 test) were monitored over an 8-week period, and the rates of corneal epithelial wound closure were recorded at 6 weeks post STZ.
Results :
T1D rats had blood glucose levels exceeding 400 mg/dL throughout the 8 weeks, and reduced body weights by 4 weeks relative to Normals, whereasT1D-INS rats had body weights and blood glucose levels comparable to Normals. Ocular surface complications were recorded in both T1D and T1D-INS female rats, but the temporal onset of defects differed. Corneal sensitivity was significantly abnormal within 3 weeks in the T1D group, whereas female T1D-INS rats had normal corneal sensitivity until 6 weeks post STZ. Tear production was significantly decreased (~3 mm) within 2 weeks of STZ in T1D rats, but normal until 5 weeks in T1D-INS rats. At 40 hr after corneal wounding, T1D rats had 40% residual wounds relative to 5% and 10%, respectively, residual wounds in Normals and T1D-INS rats.
Conclusions :
Thus, the onset of corneal complications was delayed in female T1D-INS rats relative to T1D animals suggesting amelioration due to insulin. Moreover, female T1D-INS rats had minimal changes in the rate of corneal wound repair relative to Normals. These data are the first to systematically monitor the onset and magnitude of corneal epithelial complications in female rats with insulin-controlled T1D.
This is a 2020 ARVO Annual Meeting abstract.