The Diabetic Ocular Environment Facilitates the Development of Endogenous Bacterial Endophthalmitis

Abstract

Purpose: : To test the hypothesis that changes in the diabetic ocular environment, namely increases in blood retinal barrier (BRB) permeability, facilitate the development of endogenous bacterial endophthalmitis (EBE).

Methods: : C57BL/6J mice were rendered diabetic with streptozotocin (STZ) for 1, 3, and 5 months duration. Mice in all groups were age-matched and had similar blood glucose levels of >300 mg/dl. Diabetic and age-matched sham injected control (nondiabetic) mice were tail vein-injected with 10⁸ cfu of a clinical ocular isolate of K. pneumoniae, a common cause of EBE in diabetics. After 4 days postinfection, all mice were euthanized and eyes harvested to evaluate the incidence of EBE by electroretinography and bacterial counts. A FITC-dextran leakage assay was used to determine the extent of BRB permeability in uninfected 1, 3, and 5 month diabetic mice.

Results: : No cases of EBE were observed among the 1 month diabetic group, suggesting that changes in the eye observed during diabetes progression had not yet occurred after one month, even though the mean blood glucose level was >400 mg/dl. Extending the time from diabetes induction to 3 months resulted in a 20% EBE rate, and incidence of EBE increased even higher to 30% among surviving animals in the 5 month diabetic group. Infected eyes had an average 1.4 x 10³ and 7.56 x 10⁴ cfu/eye for the 3 and 5 month diabetic groups, respectively. Retinal function was lost to a significant degree in those groups. There was no difference in BRB permeability between control and 1-month uninfected diabetic mice. However, 3 and 5 month diabetic mice had significantly greater BRB permeability than control mice, suggesting that changes in vascular permeability occurred in the eyes of 3 and 5 month uninfected diabetic mice. These results suggest that increasing the time from STZ diabetes induction to 3 and 5 months resulted in an ocular environment more conducive to the development of EBE.

Conclusions: : It is well-recognized that during the course of diabetes, the BRB becomes more permeable, however, it is unknown whether increases in BRB permeability facilitates the migration of bacteria from the vasculature into the eye, resulting in EBE. These results show a correlation between an increase in BRB permeability and an increase in EBE incidence, supporting the hypothesis that changes in the diabetic eye contribute to development of EBE.

Keywords: bacterial disease • endophthalmitis • diabetes