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


CONCLUSIONS
Interactions of AGEs, TGF-beta, TNF-alpha and alpha(v)beta(3) integrin might be involved in pathogenesis of proliferative diabetic retinopathy fibrovascular proliferation.
Abu El-Asrar
Ahmed M
AM
Department of Ophthalmology, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa <abuasrar@KSU.edu.sa>
Missotten
Luc
L
Geboes
Karel
K
D018952:Antigens, CD34 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D019773:Epiretinal Membrane / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D012171:Retinal Vessels / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018952:Antigens, CD34; D017127:Glycation End Products, Advanced; D016023:Integrins; D019394:Ki-67 Antigen; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha