Preliminary Study On The Mechanism Of 1,25-Dihydroxyvitamin D₃ In The Pathogenesis Of Diabetic Retinopathy

Objective: This study aimed to investigate the effect of 1,25?OH?₂D₃ on the pathogenesis of diabetic retinopathy?diabetic,retinopathy,DR?from the aspect of immunity and inflammation.Method: Blood samples were obtained from 24 patients with proliferative DR?PDR?,24 patients with non-proliferative DR?NPDR?and 26 normal controls.ELISA was performed to estimate the serum levels of 1,25?OH?₂D₃.Peripheral blood mononuclear cells?PBMCs?were cultured with or without 1,25?OH?₂D₃ in the presence of anti-CD3 and anti-CD28 antibodies 3 days to detect the secretion of cytokines and cell proliferation.The Cell Counting Kit was used to determine the rate of cell proliferation.The FACS cytometric bead array system was used to analyse cytokine levels in the serum and culture supernatant.Results: 1.The serum 1,25?OH?₂D₃ levels were significantly decreased in PDR compared with the NPDR?P<0.05?and normal controls?P<0.05?.2.Serum IFN-? levels were significant reduced in PDR compared with normal controls?P<0.05?.Serum IL-6 was significantly increased in PDR compared with the normal controls?P= 0.015?.3.A primary experiment with different concentrations of 1,25?OH?₂D₃ showed that the treatment with 1,25?OH?₂D₃ significantly inhibited the proliferation of PBMCs from normal controls.Furthermore,results showed that its inhibitory effect was in a dose-dependent manner.At the concentration of 1×10-7 mol/l,1,25?OH?₂D₃ could induce a significant suppression on PBMC proliferation,this concentration was therefore used in the subsequent experiments.4.PBMCs were separated from DR patients and healthy controls,and cultured with anti-CD3 and anti-CD28 antibodies,we observed a significantly higher cell proliferation in patients with PDR compared with patients with NPDR and normal controls.Furthermore,exposure to 1,25?OH?₂D₃ significantly inhibited the cell proliferation in DR patients and normal controls.5.The experiment revealed significantly increased expression of IFN-?,TNF-?,IL-6 and IL-17 A by activated PBMCs from patients with PDR.6.The experiment showed that 1,25?OH?₂D₃ could significantly inhibit the expression of IFN-?,TNF-?,IL-6 and IL-17 A in DR groups and normal controls group.Conclusion: 1,25?OH?₂D₃ has immunomodulatory effects on DR patients and may play a protective role in patients with DR.