title: Expression of advanced glycation end products and related molecules in diabetic fibrovascular epiretinal membranes.
abstract: 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.
authors.affiliation: Department of Ophthalmology, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa <abuasrar@KSU.edu.sa>
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
authors.forename: Luc
authors.initials: L
authors.lastname: Missotten
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
mesh_terms: 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*
chemical_list: D018952:Antigens, CD34; D017127:Glycation End Products, Advanced; D016023:Integrins; D019394:Ki-67 Antigen; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha