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L. K. Julian, E. J. Kuiper, M. Iribarne, I. Vogels, R. A. Dodds, A. M. Suburo, R. O. Schlingemann; Experimental Induction of PVR-Like Lesions in CTGF-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5776.
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Connective tissue growth factor (CTGF) has been identified as a major factor in physiological wound healing and pathologic conditions associated with fibrosis. It has been identified within PVR membranes. CTGF vitreal concentration can be correlated with degree of fibrosis in vitreoretinal disorders. Therefore, we reasoned that experimental induction of PVR-like lesions in mice would depend on the CTGF gene dosage.
Experimental PVR was induced in wild type (WT, CTGF+/+) and heterozygous (HZ, CTGF+/-) C57Bl6/J male mice using intravitreal injections of dispase. Mice were examined under anesthesia to evaluate retinal changes 1, 2, 4-5 and 9-12 weeks after dispase. A trained blinded observer recorded relevant ophthalmoscopic signs that were quantitatively evaluated according to predetermined rules.
Large retinal detachments were detected 1 week after injection but healed spontaneously. Haemorrhages were frequently found and usually worsened during weeks 1 and 2 but disappeared with time. The injection site usually remained open and surrounded by an elevated rim. Two kinds of subretinal lesions could be observed: solid deposits or tunnels. The latter represent localized detachments or invaginations of the outer retinal layers. Epiretinal lesions included retinal folds and membranes, accompanied by vascular traction and late detachments. Earlier development of lesions and higher PVR scores were a constant finding in HZ mice at all times after injection. During weeks 10-12 about 40% of WT mice exhibited retinal folds, epiretinal membranes, late detachments and vitreal exudates and strands. More than 60% of HZ mice showed similar lesions and nearly 90% of them had subretinal lesions extending through the whole retinal surface.
Contrary to our hypothesis, PVR-like lesions were more severe en CTGF-deficient than in WT mice. Although this growth factor is required for fibrosis, its absence would increase vulnerability of the retina. Lesions induced by dispase, a collagenase, would be aggravated by CTGF deficiency since this factor is required for expression of extracellular matrix molecules. Ultimately, membrane formation would not be avoided by decreased expression of CTGF unless the initial process leading to PVR has been extinguished.
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