inositol-1-4-5-trisphosphate and Diabetic-Retinopathy

An experimental model of diseased pericytes was established by using cultured bovine retinal capillary pericytes in high--glucose medium. The high glucose stimulated polyol pathway, reduced cellular myo-inositol content and disturbed inositol phospholipid metabolism which resulted in a decrease in inositol trisphosphate (IP3) level. The correlation of suppressed IP3 levels with reduced DNA synthesis was evident. These findings suggested the biochemical mechanism by which retinal pericytes degenerate in high glucose. To supplement myo--inositol and/or an aldose reductase inhibitor to the high--glucose medium largely reversed the suppressed IP3 level and the decreased DNA synthesis. Therefore, these two manipulations may be considered as in vitro therapy to treat sick pericytes induced by high glucose.

Topics: Animals; Arterioles; Capillaries; Cattle; Cells, Cultured; Diabetic Retinopathy; DNA; Glucose; Inositol; Inositol 1,4,5-Trisphosphate; Phosphatidylinositols; Retinal Artery

An experimental pathologic model of pericyte drop-out was established with capillary pericytes in culture medium of high glucose concentration. The high glucose activated the sorbitol pathway, reduced the intracellular myo-inositol content and disturbed the inositol phospholipid metabolism which resulted in a decrease in the inositol trisphosphate (IP3) level. The correlation of suppressed IP3 level with reduced DNA synthesis was evident, suggesting the mechanism that retinal pericytes degenerated in high glucose concentration. In vitro test of adding myo-inositol and/or aldose reductase inhibitor to the high-glucose medium reversed the inositol phospholipid metabolism and the decreased DNA synthesis, which could hold promise for the clinical prevention and treatment of early diabetic retinopathy.

Topics: Animals; Cattle; Cell Survival; Cells, Cultured; Diabetic Retinopathy; DNA; Inositol 1,4,5-Trisphosphate