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Insulin Treatment Ameliorates Impaired Corneal Reepithelialization in Diabetic Rats

¹ Departments of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
² Department of Opthalmology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania

Address correspondence and reprint requests to Dr. Ian S. Zagon, Department of Neural and Behavioral Sciences, H109, The Milton S. Hershey Medical Center, Penn State College of Medicine, 500 University Dr., Room C3729, Hershey, PA 17033. E-mail: isz1{at}psu.edu

Abbreviations: STZ, streptozotocin

Patients with diabetes are at an increased risk for developing corneal disorders, often as a result of surgical and nonsurgical trauma. This study investigated whether intensive treatment of diabetes with the goal of maintaining blood glucose concentrations close to the normal range could ameliorate the delayed corneal wound healing found in animals with uncontrolled diabetes. Diabetes was induced with streptozotocin, and rats were divided into groups based on the degree of blood glucose control: 1) not treated with insulin implants (DB group), 2) receiving insulin implants and determined to be normoglycemic (DB-IN group), and 3) normal, nondiabetic animals serving as controls. Immediately before wounding at 9 or 11 weeks after the induction of the diabetic state, corneal thickness and corneal sensitivity of the DB and DB-IN groups were comparable with controls. DB, but not DB-IN, rats exhibited subnormal intraocular pressure. At 9 and 11 weeks after the onset of diabetes, the corneas of the right and left eyes, respectively, were abraded by mechanical scraping. The DB rats had residual corneal epithelial defects that ranged from 23% to 5.6-fold larger compared with the control group and a rate of healing that was 19% slower than control animals. The DB-IN group had healing characteristics similar to the control group. DNA synthesis in the peripheral cornea and conjunctiva, but not the limbus, of DB animals was reduced 50 and 91%, respectively, from control levels. Cell proliferation in the DB-IN group was comparable with the control group, with the exception of a 72% increase in the peripheral cornea in the DB-IN group. These results indicate that intensive therapy with insulin, which establishes normoglycemia in rats with diabetes, prevents the delay in wound healing of ocular surface epithelium observed in poorly controlled diabetic animals.

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				I. S. Zagon, M. S. Klocek, J. W. Sassani, and P. J. McLaughlin Use of Topical Insulin to Normalize Corneal Epithelial Healing in Diabetes Mellitus Arch Ophthalmol, August 1, 2007; 125(8): 1082 - 1088. [Abstract] [Full Text] [PDF]