Imbalanced levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of patients with proliferative diabetic retinopathy.
A role for vascular endothelial growth factor (VEGF) has been clearly implicated in the pathogenesis of proliferative diabetic retinopathy (PDR). However, other molecules and mechanisms may be operating independently, or in conjunction with VEGF in the pathogenesis of this disease. Therefore, we made an attempt to comparatively investigate the levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of subjects with Proliferative Diabetic Retinopathy (PDR) compared to control subjects. The vitreous and plasma concentrations of VEGF, EPO (Erythropoietin) and PEDF (Pigment Epithelium Derived Factor) were measured using Enzyme Linked Immunosorbent Assay (ELISA) and the postmortem retinal tissue was subjected to Western blot analysis. The mean vitreous and plasma levels of VEGF and EPO in patients with PDR were significantly (p<0.001) higher than those in subjects without diabetes. Conversely, the vitreous and plasma levels of PEDF were significantly (p<0.001) lower in the PDR patients compared to control subjects. Multivariate logistic-regression analyses indicated that EPO was more strongly associated with PDR than VEGF. The protein expression of the VEGF and EPO in the retinal tissue was significantly higher in PDR and diabetes without complication groups compared to controls. Compared to controls, the protein expression of PEDF was significantly lower in retinal tissues from diabetes patients without complications and in patients with PDR. The fact that the vitreous and plasma levels and the retinal tissue protein expression of EPO were strongly associated with PDR implies a definite role of 'hypererythropoietinemia' in neovascularization processes.
Madras Diabetes Research Foundation and Dr. Mohans' Diabetes Specialities Centre, Gopalapuram, Chennai-600 086, India.
Nithyakalyani
N
Mohan
Finny
F
Monickaraj
Muthuswamy
M
Balasubramanyam
Mohan
M
Rema
Viswanathan
V
Mohan
D000328:Adult; D042501:Angiogenic Proteins / Q000097:blood / Q000378:metabolism*; D043165:Angiostatic Proteins / Q000097:blood / Q000378:metabolism*; D015153:Blotting, Western; D003930:Diabetic Retinopathy / Q000097:blood / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000097:blood / Q000378:metabolism; D005125:Eye Banks; D005136:Eye Proteins / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D015843:Serpins / Q000097:blood / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000097:blood / Q000150:complications / Q000378:metabolism*; D014822:Vitreous Body / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D042501:Angiogenic Proteins; D043165:Angiostatic Proteins; D004921:Erythropoietin; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C554270:EPO protein, human; C467484:VEGFA protein, human