A role for connective tissue growth factor in the pathogenesis of choroidal neovascularization.
OBJECTIVE
To evaluate the expression of connective tissue growth factor (CTGF) in choroidal neovascular membranes from patients with age-related macular degeneration and the effect of CTGF on choroidal endothelial cell (CEC) function.


METHODS
Using immunohistochemical methods, we analyzed CTGF expression in 13 surgically excised choroidal neovascular membranes related to age-related macular degeneration. The expression of CTGF in retinal pigment epithelial and CEC cultures was determined by means of reverse transcriptase polymerase chain reaction and Western blot, and its regulation by vascular endothelial growth factor and transforming growth factor beta was determined. The effects of CTGF on bovine CEC proliferation, attachment, migration, and tube formation were measured.


RESULTS
Vascularized human choroidal neovascular membranes showed strong CTGF immunoreactivity. Double staining disclosed colocalization of CTGF with retinal pigment epithelial cells and CECs. The CTGF induced a significant increase in attachment and migration of CECs; however, it did not stimulate CEC proliferation. The CTGF protein was up-regulated in retinal pigment epithelial cells and CECs by stimulation with transforming growth factor beta and vascular endothelial growth factor, respectively.


CONCLUSIONS
The expression of CTGF in choroidal neovascular membranes, its regulation by angiogenic growth factors, and its proangiogenic effects on CEC function suggest that CTGF may play a role in the pathogenesis of choroidal neovascularization. Clinical Relevance Multiple growth factors are involved in the pathogenesis of choroidal neovascularization in age-related macular degeneration.
He
Shikun
S
Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles 90033, USA.
Jin
Man Lin
ML
Worpel
Vanessa
V
Hinton
David R
DR
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000209:etiology* / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000494:pharmacology / Q000502:physiology*; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D008222:Lymphokines / Q000494:pharmacology; D008268:Macular Degeneration / Q000150:complications; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C526317:CCN2 protein, human; D016228:Endothelial Growth Factors; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D055513:Connective Tissue Growth Factor