Abstract
Purpose :
Patients of diabetes mellitus suffer from high incidence of corneal epithelial defects, ocular surface infections and dry eye disease. Ocular surface glycocalyx, mucins and goblet cells play a critical role to keep the ocular surface hydrated and protected from pathogens. We have previously shown that hyperglycemia can compromise ocular surface epithelial barrier function. The goal of the present study was to investigate the effect of diabetes mellitus on tear film, glycocalyx, mucins and goblet cells and to test whether restoration of euglycemia by insulin treatment has ameliorative effects on hyperglycemia-mediated ocular surface damage.
Methods :
Streptozotocin-induced and db/db mouse models of type 1 and type 2 diabetes were used. Tears were quantified using phenol red thread and corneal keratopathy was visualized with slit lamp after fluorescein staining. Eyes were harvested at week1, 2 and 4 after diabetes. Glycocalyx was stained with wheat germ agglutinin and whole cornea mounts were imaged using confocal microscope. Tissue sections were used for goblet cell staining with PAS and imaged using brightfield microscope. Mucin gene expression was quantified in corneal tissue using real time PCR. Mice were implanted with subcutaneous insulin pellets. Effect of insulin treatment on diabetes-associated changes in tear film, glycocalyx, goblet cells and mucins were examined.
Results :
Our data shows that type 1 and type 2 diabetes caused a 60% and 30% decrease in tear film volume and resulted in corneal keratopathy score of 10 and 8, respectively. A 65% and 45% decrease in glycocalyx area was noted in the corneas of type 1 and type 2 diabetic mice. Goblet cell number was decreased by 40% and 16%. Diabetes mellitus also modulated gene expression of membrane-tethered mucins. Treatment of diabetic mice with insulin pellets restored blood glucose levels to euglycemia. Insulin treatment reduced the severity of diabetes-mediated corneal keratopathy and remarkably prevented diabetes-mediated decrease in tear secretion, glycocalyx area and goblet cell number.
Conclusions :
Diabetes mellitus causes damage to ocular surface and more detrimental effect was observed with higher levels of hyperglycemia due to type 1 diabetes as compared to type 2 diabetes mellitus. Restoration of euglycemia by insulin treatment remarkably prevented diabetes-mediated damage to tear film and ocular surface.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.