Roles of Cytokines in Diabetic Retinopathy

Preretinalproliferative membrane formation, which is regulated by various cytokines, is a veryimportant step in the pathogenesis of proliferative diabetic retinopathy. In addition tovascular endothelial growth factor, transforming growth factor β2 (TGF-β2) has beenshown to play a key role in preretinal membrane formation caused by retinal metabolicabnormalities. Interleukin 6 (IL-6) has also been reported to be involved in thepathogenesis of diabetic retinopathy. In this study, to investigate the roles of thesecytokines in the pathogenesis of diabetic retinopathy, we searched for systemic and/orocular factors relevant to TGF-β2 and IL-6 in diabetic eyes.
The concentrations of TGF-β2 and IL-6 in the vitreous fluid derived from 92 eyes of92 diabetic patients (mean ±SD age, 50.5 ± 12.3 years) and 4 eyes of 4 nondiabeticpatients (mean ±SD age, 60 ± 14.7 years) were measured using enzyme-linked immunosorbentassay kits (R&D System, Minn). The mean age was not different between the 2 groups.Four eyes from the patients with background diabetic retinopathy and 86 eyes from thepatients with active proliferative diabetic retinopathy were included. Vitreous fluid wasobtained during vitrectomy under the approval from the authority of the institutionalreview board with informed consent from each patient. The correlation between theconcentrations and the clinical factors was examined statistically.
The concentrations of IL-6 in proliferative diabetic retinopathy eyes ranged from3.1 to 191.0 pg/mL, with a mean ±SD of 37.6 ± 43.6 pg/mL (n=20), which was significantlyhigher than those in nondiabetic eyes (3.2 ± 2.3 pg/mL, n=3) (Mann-Whitney U test,P=0.01). Multivariate regression analysis using a logistic model was performed to searchfor the relevant factor(s) to the concentration of IL-6 among duration of diabetes, bloodglucose control evaluated by hemoglobin A_1C values, grade of diabeticretinopathy, treatment by laser photocoagulation, grade of vitreous hemorrhage, macularedema, tractional retinal detachment, posterior vitreous detachment, and the concentrationof vascular endothelial growth factor. The analysis revealed that the concentration ofIL-6 was significantly correlated with hemoglobin A_1C (n=18, P=0.003). Thiscorrelation is consistent with the result from the report that high glucose levelsstimulated IL-6 production from monocytes. These results show that IL-6 in eyes withdiabetic retinopathy was associated with poor diabetic control, which may cause diabeticretinopathy progression.
The concentration of total TGF-β2 ranged from 1400 to 5200 pg/mL with a mean ±SDof 2616 ±1135 pg/mL (n=15). Multivariate regression analysis was also performed to searchfor the relevant factor(s) to the concentration fo TGF-β2 among hemoglobin A_1C ,grade of retinopathy, grade of vitreous hemorrhage, macular edema, and tractional retinaldetachment. Transforming growth factor β2 was significantly correlated with the grade ofvitreous hemorrhage (n=14, P=0.004) (vitreous hemorrhage was graded by the visibility ofocular fundus). Transforming growth factor β2 has been reported to be involved in theformation of proliferative membranes and in the contraction of those membranes. Theseresults indicate that TGF-β2 was involved in the pathogenesis of vitreous hemorrhage.
This study reveals the correlation between IL-6 and hyperglycemia and between TGF-β2and vitreous hemorrhage in proliferative diabetic retinopathy eyes, which suggests thatIL-6 and TGF-β2 play important roles in the pathogenesis of diabetic retinopathy.

投稿截止日期99年10月1日