Expression of connective tissue growth factor and its potential role in choroidal neovascularization.
BACKGROUND
To determine the expression of connective tissue growth factor (CTGF) in choroidal neovascularization.


METHODS
Surgically excised choroidal neovascular membranes (CNVMs) were obtained at vitrectomy from eight eyes with age-related macular degeneration, five eyes with high myopia, and two eyes with angioid streaks. Light microscopic immunohistochemical analysis was performed to detect CTGF, transforming growth factor beta 1 (TGF-beta1), vascular endothelial growth factor (VEGF), pancytokeratin, and smooth muscle actin (SMA).


RESULTS
CNVMs were classified by fibrotic status as cellular CNVM, moderate fibrous CNVM, and extensive fibrous CNVM. CTGF expression was found in vascular cells, stromal cells, and retinal pigment epithelium (RPE) cells. For the stromal cells, fibroblastlike cells were most strongly positive for CTGF. CTGF immunoreactivity in the stroma was stronger in the fibrous CNVMs than in the cellular CNVMs. Immunohistochemical analysis of serial sections revealed colocalization of CTGF with TGF-beta1 and VEGF; colocalization of CTGF with pancytokeratin and SMA was also found.


CONCLUSIONS
Our findings suggest that transdifferentiated RPE cells and vascular cells possess remarkable CTGF expression in CNVMs. This expression of CTGF may stimulate fibroblasts to produce extracellular matrix and may promote angiogenesis in vascular cells. Colocalized TGF-beta1 and VEGF may also contribute the upregulation of CTGF.
Watanabe
Daisuke
D
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takagi
Hitoshi
H
Suzuma
Kiyoshi
K
Oh
Hideyasu
H
Ohashi
Hirokazu
H
Honda
Yoshihito
Y
D000368:Aged; D020256:Choroidal Neovascularization / Q000378:metabolism*; D055513:Connective Tissue Growth Factor; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014821:Vitrectomy
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor