Expression of advanced glycation end products and related molecules in diabetic fibrovascular epiretinal membranes

P>Purpose: To investigate associations between expressions of advanced glycation end products (AGEs), transforming growth factor-beta (TGF-beta), tumour necrosis factor-alpha (TNF-alpha) and integrins and correlations between their expression and level of vascularization and proliferative activity in diabetic fibrovascular epiretinal membranes. Methods: Membranes from eight patients with active proliferative diabetic retinopathy and nine patients with inactive proliferative diabetic retinopathy were studied by immunohistochemistry. Results: Blood vessels expressed AGEs, TGF-beta, TNF-alpha and alpha(v)beta(3) integrin in 5, 13, 8 and 8 membranes, respectively. Stromal cells expressed AGEs, TNF-alpha and alpha(v)beta(3) integrin in 15, 13 and 3 membranes, respectively. There was no immunoreactivity for alpha(v)beta(5), alpha(5)beta(1) and alpha(2)beta(1) integrins. There were significant correlations between number of blood vessels expressing CD34 and number of blood vessels expressing AGEs (r(s) = 0.496; P = 0.043), TGF-beta (r(s) = 0.777; P < 0.001) and TNF-alpha (r(s) = 0.699; P = 0.002). There were significant correlations between number of blood vessels expressing AGEs and number of blood vessels expressing TGF-beta (r(s) = 0.532; P = 0.028) and TNF-alpha (r(s) = 0.626; P = 0.007). The correlation between number of blood vessels expressing TNF-alpha and alpha(v)beta(3) integrin was significant (r(s) = 0.617; P = 0.008). Number of blood vessels expressing CD34 (P = 0.001), TGF-beta (P = 0.006) and TNF-alpha (P = 0.002) and stromal cells expressing AGEs (P = 0.001) and TNF-alpha (P = 0.004) were significantly higher in active membranes than in inactive membranes. Conclusion: Interactions of AGEs, TGF-beta, TNF-alpha and alpha(v)beta(3) integrin might be involved in pathogenesis of proliferative diabetic retinopathy fibrovascular proliferation.