Restoration of endogenous substance P is associated with inhibition of apoptosis of retinal cells in diabetic rats

• Retinal cell apoptosis may happen at an early time of diabetes.
• High concentration of glucose may inhibit expression of SP.
• Normal level of SP is critical for the homeostasis of the retinal neurons.
• Reduction of SP may be associated with retinal apoptosis.
• Restoration of normal level of SP in the retina is of potential values in prevention of the retinal injury.

This study was designed to investigate the alterations of substance P (SP) and its correlation with apoptosis of the retinal neurons in diabetic rats.The study was carried out with diabetic rats induced by streptozotocin. Changes of SP and its mRNA were examined using enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. The effect of restoration of SP level by capsaicin (20 mg/kg, s.c.) on the apoptosis of the retinal cells was studied. The apoptosis was evaluated by change of ratio of the apoptotic cells and caspase-3 activity in the retina.It was found that increase in apoptosis of retinal cells, by 3.5 fold of control, was accompanied by reduction of SP, by 28% in protein and 32% in the mRNA in the retina at 10 weeks of induction of diabetes, compared to the controls. Capsaicin significantly elevated endogenous SP, by 29% in the mRNA and 17% in protein in the retina, with marked inhibition of the apoptosis and the activity of caspase-3 in the diabetic rats.Induction of diabetes leads to the increase of cell apoptosis and the decrease of SP in the retina. The reduction of the endogenous SP and the increase of the cell apoptosis in the retina of the diabetic rats were reversed by pretreatment with capsaicin. Restoration of SP in the retina may be a novel option for prevention of the retinal injury during development of diabetes.