Accumulation of NH2-terminal fragment of connective tissue growth factor in the vitreous of patients with proliferative diabetic retinopathy.
OBJECTIVE
To evaluate the expression of connective tissue growth factor (CTGF) and its fragments in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to localize CTGF expression in associated preretinal membranes.


METHODS
Vitreous was obtained from 24 patients with active PDR, 4 patients with quiescent PDR, and 23 patients with other retinal diseases and no diabetes, including 5 patients with vitreous hemorrhage. Enzyme-linked immunosorbent assay was used to determine levels of whole CTGF and its NH2- and COOH-terminal fragments. Preretinal membranes from three patients with active PDR were stained immunohistochemically for the presence of CTGF and cell type-specific markers.


RESULTS
A significant increase in NH2-terminal CTGF fragment content was found in vitreous samples from patients with active PDR when compared with samples from nondiabetic patients (P<0.0001) or patients with quiescent PDR (P=0.02). Levels of NH2-terminal CTGF were also greater in vitreous samples from diabetic patients with vitreous hemorrhage compared with samples from nondiabetic patients with vitreous hemorrhage (P=0.02). Vitreous levels of whole CTGF were similar in all groups. COOH-terminal fragments of CTGF were not detected. CTGF immunoreactivity was predominantly localized to smooth muscle actin-positive myofibroblasts within active PDR membranes.


CONCLUSIONS
-NH2-terminal CTGF fragment content is increased in the vitreous of patients with active PDR, suggesting that it plays a pathogenic role or represents a surrogate marker of CTGF activity in the disorder. The localization of CTGF in myofibroblasts suggests a local paracrine mechanism for induction of fibrosis and neovascularization.
Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033, USA. dhinton@usc.edu
David R
DR
Hinton
Christine
C
Spee
Shikun
S
He
Stephen
S
Weitz
William
W
Usinger
Laurie
L
LaBree
Noelynn
N
Oliver
Jennifer I
JI
Lim
D055513:Connective Tissue Growth Factor; D003930:Diabetic Retinopathy / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D014821:Vitrectomy; D014822:Vitreous Body / Q000737:chemistry* / Q000473:pathology
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D055513:Connective Tissue Growth Factor