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Y.-Z. Le, Y. Bai, M. Zhu; Relationship Between the RPE-Produced VEGF and the Outer Blood-Retina Barrier Function. Invest. Ophthalmol. Vis. Sci. 2008;49(13):857.
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Outer blood-retina barrier (BRB) is the major BRB and responsible for approximately 70 percent of blood circulation in the retina. It has been suggested that the retinal pigment epithelium (RPE)-produced vascular endothelial growth factor (VEGF or VEGF-A) plays an important role in the regulation of the outer BRB function. To define the role of the RPE-produced VEGF in outer BRB function, we generated inducible RPE-specific VEGF knockout mice and induced VEGF disruption after choroidal development. These conditional VEGF knockout mice had no apparent developmental defects. We are using these mice to determine if the RPE-produced VEGF plays a role in outer blood barrier function.
Inducible RPE-specific VEGF knockout mice were generated by mating the floxed VEGF mice with our tetracycline-inducible RPE-specific Cre mice. The RPE-specific VEGF disruption was induced at postnatal day 5-7 (P5-7). The disruption of the RPE-produced VEGF was confirmed by Western blot and immunohsitochemistry analysis, the choroidal density was determined by a semi-quantitative assay developed in our laboratory, the retinal vasculature was examined by vessel staining, the RPE integrity was analyzed by quantification of RPE density, and the retinal integrity was determined by examination of retinal morphology and retinal function.
Postnatal disruption of the RPE-produced VEGF did not cause observable defects in choroidal vasculature, retinal vasculature, RPE, and photoreceptor morphology and function at weaning age. The conditional VEGF knockout mice generated this way were then kept for ageing under normal conditions. In our preliminary characterization, these conditional VEGF knockout mice demonstrated photoreceptor degeneration and increased auto-fluorescence in the RPE region after a year. A detailed characterization is in progress.
Loss of the RPE-produced VEGF may affect the function of the outer blood retina barrier, which in turn, causes age-dependent photoreceptor degeneration under normal conditions, a situation similar to that in dry-form of the age-related macular degeneration. We are actively investigating the underline mechanisms.
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