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Microvasc Res. 2009 Jun;78(1):119-27. doi: 10.1016/j.mvr.2009.02.005. Epub 2009 Mar 10.

Photoreceptor degeneration and retinal inflammation induced by very low-density lipoprotein receptor deficiency.

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Department of Cell Biology, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.


Our previous studies have shown that very low-density lipoprotein receptor (VLDLR) is a negative regulator of the Wnt pathway. The present study showed that VLDLR gene knockout (Vldlr(-/-)) mice displayed impaired cone ERG responses at early ages. Immunostaining of mid-wavelength cones showed significantly decreased cone densities in the retina and shortened cone outer segments in Vldlr(-/-) mice. At older ages, Vldlr(-/-) mice displayed declined rod ERG responses, decreased layers of photoreceptor nuclei, reduced rhodopsin levels and decreased levels of 11-cis retinal, the chromophore of visual pigments. As shown by fluorescein angiography and permeability assay, Vldlr(-/-) mice had severe retinal vascular leakage. ZO-1, a tight junction protein, was down-regulated in Vldlr(-/-) mouse retinae, further supporting the impaired blood-retinal barrier. Double staining of pericytes and endothelial cells in retinal sections revealed that neovasculature in Vldlr(-/-) mice lacks pericyte coverage, suggesting impaired maturation of retinal vasculature in Vldlr(-/-) mice. Staining of adherent leukocytes in the retinal vasculature revealed significant leukostasis in Vldlr(-/-) mice. Moreover, Vldlr(-/-) mice displayed up-regulated expression of multiple pro-inflammatory factors and activated NF-kappaB and HIF-1 alpha, key regulators of inflammation. These findings suggest that deficiency of VLDLR leads to retinal degeneration and inflammation.

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