Expression of angiogenic and fibrogenic factors in proliferative vitreoretinal disorders.
OBJECTIVE
To investigate the expression of connective tissue growth factor (CTGF) in the retina of human subjects with diabetes mellitus, and CTGF, CD105, and gelatinase B in proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) epiretinal membranes.


METHODS
Twelve donor eyes from six subjects with diabetes mellitus, 10 eyes from five nondiabetic subjects, 14 PDR membranes, and five PVR membranes were studied by immunohistochemical techniques. In situ zymography was used to examine gelatinolytic activity in four PDR membranes.


RESULTS
In nondiabetic retinas, there was no immunoreactivity for CTGF. Diabetic retinas showed immunoreactivity for CTGF in ganglion cells and microglia. Vascular endothelial cells in PDR membranes expressed CTGF, CD105, and gelatinase B in 10 (71.4%), 11 (78.6%), and 5 (35.7%) membranes, respectively. Myofibroblasts in PDR membranes expressed CTGF, and gelatinase B in 14 (100%), and 6 (42.9%) membranes, respectively. There was a significant correlation between the number of blood vessels expressing the panendothelial marker CD34 and the number of blood vessels expressing CTGF (r = 0.7884; P = 0.0008), and CD105 (r = 0.6901; P = 0.0063), and the number of myofibroblasts expressing CTGF (r = 0.5922; P = 0.0257). There was a significant correlation between the number of myofibroblasts expressing alpha-smooth muscle actin and the number of myofibroblasts expressing CTGF (r = 0.8393; P = 0.0002). In situ zymography showed the presence of gelatinolytic activity in vascular endothelial cells in PDR membranes. Myofibroblasts in PVR membranes expressed CTGF, and gelatinase B.


CONCLUSIONS
These results suggest a possible role of CTGF, CD105, and gelatinase B in the pathogenesis of proliferative vitreoretinal disorders.
Abu El-Asrar
Ahmed M
AM
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
Van den Steen
Philippe E
PE
Al-Amro
Saleh A
SA
Missotten
Luc
L
Opdenakker
Ghislain
G
Geboes
Karel
K
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D003920:Diabetes Mellitus / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism; D019773:Epiretinal Membrane / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism; D014018:Tissue Distribution
D000199:Actins; D015703:Antigens, CD; C526317:CCN2 protein, human; C064206:ENG protein, human; D000071063:Endoglin; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D055513:Connective Tissue Growth Factor; D020780:Matrix Metalloproteinase 9