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V.B. Mahajan, A. Assefnia, S. Tsang, D. Farber, P.J. McDonnell, B.J. Mondino; Connective Tissue Growth Factor Function in the Developing Eye . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2175.
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Purpose: To better understand the molecular mechanisms by which distinct ECMs are formed in the eye, transcriptional profiling was used to identify candidate genes that might contribute to corneal transparency. To confirm the biological significance of these results, we studied a mouse knockout model for the Connective Tissue Growth Factor (CTGF) candidate gene. Methods:Transcriptional profiling was performed on cultured corneal and scleral fibroblasts using Affymetrix DNA microarrays and a Bayesian statistical framework. A CTGF knockout mouse was examined by standard histological methods. Results: CTGF RNA expression was elevated in corneal fibroblasts when compared with scleral fibroblasts. Examination of E18.5 CTGF knockout eyes revealed several developmental abnormalities. While CTGF–/– sclera appeared normal, CTGF–/– corneas demonstrated hypertrophic cells and a poorly organized lamellar structure resulting in corneal opacity. Furthermore, the anterior chamber showed a persistent pupillary membrane. Fetal hyaloid vessels also showed a delayed regression pattern in the vitreous cavity with more numerous, large diameter vessels. Immunohistochemistry studies showed a normal number of localized macrophages. Finally, consistent with the major CTGF effect on chondrogenesis, orbital bone abnormalities were observed. Conclusions: Comparative expression profiling is an important method to identify candidate genes for ECM remodeling, and mouse knockouts can provide functional confirmation of gene activity. Exploration of CTGF signaling pathways will help reveal the molecular mechanisms underlying corneal opacity and persistent fetal vasculature.
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