Abstract
Purpose: :
The enzyme indoleamine 2,3-dioxygenase (IDO) belongs to the family of heme-containing oxidoreductases and is involved in tryptophan metabolism. Besides its well documented activity in regulating the maturation and recruitment of regulatory T-cells, tissue-specific expression of IDO during inflammation represents a self-protection mechanism to limit antigen-specific immune responses. Previous studies have shown that IDO is expressed in the retina and its expression varies in response to acute inflammatory stimuli. Diabetic retinopathy, DR, is thought to involve chronic sub-clinical inflammation. Here we wanted to determine whether expression of IDO is altered in the diabetic retina.
Methods: :
Db/db mice, a model of type 2 diabetes, were sacrificed at 12-14 weeks of age. Human post-mortem retinas from diabetic and non diabetic donors, were obtained from Georgia Eye Bank. Western blotting and immunoistochemical analyses were conducted to determine IDO expression in the murine and human diabetic retina and compared to non diabetic controls.
Results: :
Immunohistochemical and Western blotting analyses showed that IDO expression was significantly reduced in db/db mice (p<0.05 versus control, n=8) as compared to age-matched normoglycemic control animals (n=8). In the post-mortem human diabetic retinas (n=6) we have also found a marked reduction of IDO expression compared to non diabetic donors (p<0.05, n=6).
Conclusions: :
Our data demonstrate, for the first time, that the immunomodulator IDO is down-regulated in the diabetic retina (murine and human), thus potentially implicating its function in maintenance of retinal anti-inflammatory protective mechanisms. The obtained results, therefore, warrant further studies to understand the mechanisms of hyperglycemia-induced downregulation of IDO and its significance in the pathogenesis of DR.
Keywords: diabetic retinopathy • inflammation • immunomodulation/immunoregulation