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J. Lee, N. Walsh, I.R. Zolfaghar, C. Xia, X. Gong, J.G. Flannery; Progression of the VLDLR –/– Retinal Phenotype With Age: Correlating Fundus Features With Histological and Functional Measures . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5251.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The VLDLR –/– mouse provides an important model of subretinal neovascularization through which therapies for human disease may be trialed. We have sought to characterize the retinal features of this strain over a one year period through a range of measures which include fundus imaging, fluorescein angiography, histology, electrophysiology and 3D vessel reconstruction. Methods: Developmental series of fundus and fluorescein angiography (FA) images were taken from VLDLR mice between the ages of 1 and 12 months. Images were analyzed for the characteristic ‘yellow spots’ found in this strain along with the number of leaky foci present at each time point. Histological sections and electrophysiology were taken from wild type and VLDLR mice at 3, 6 and 12 months.Three–dimensional reconstructions of retinal flat mounts were performed following perfusion of animals with a lipophilic vessel dye, and quantitative measurements of vessel length and volume were computed from these reconstructions. Results: At the earliest time point examined, leaky foci evident on FA corresponded to the areas of hypopigmentation observed on color fundus images. An increase in the number of leaky foci was observed up until approximately 10 weeks of age, after which most if not all leaky spots were observed to spontaneously resolve. Areas of hypopigmentation were observed to increase and persist up until the oldest ages studied. Over the one year period, outer nuclear layer thickness was observed to decline and outer segments structure was disrupted. At 3 months of age, measures of a– and b–wave amplitude were not significantly different from age–matched wild type mice. At 6 and 12 months of age, b–wave amplitudes were not significantly different from either the 3 month or control values, and a 40% reduction in a–wave amplitude was observed. Conclusions: Histological sections and 3D vessel reconstruction at the later time points argue against a spontaneous resolution of the vessels, but rather a maturation of the existing vessels. Degeneration of the photoreceptor layer with age is reflected by a reduction in outer nuclear layer thickness and a significant reduction in a–wave amplitude at the 6 and 12 month time points. These results contribute to our understanding of VLDLR phenotype which is important in evaluating therapeutic modalities for retinal neovascularization.
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