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X. Qiao, A. Jiang, H. Gao; VLDL Receptor Knockout Does Not Alter the Early Postnatal Development of Retinal Vasculature. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3347.
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It has been well documented that subretinal neovascularization (SNV) in VLDL receptor knockout (vldlr-/-) mice models retinal angiomatus proliferation (RAP). This study examines the role of VLDLR in retinal vascular formation during the development.
The level and cellular origin of VLDLR expression in the mouse retina during postnatal development were determined by Western blot and immunofluorescent staining. The development of retinal vasculature network was examined at various postnatal days in the whole mount retina after isolectin staining under a fluorescent confocal microscope. Littermates from heterozygous (vldlr+/-) breeders were used for comparison of the effect of VLDLR gene on retinal vessel development.
Low level of VLDLR protein was detected in the retina at postnatal day 5 (P5). The level increased and peaked around P10 to P14 before it reduced to a lower level in adult mice. Immunofluorescent staining revealed intense signals of VLDLR in the outer retina near outer limiting membrane beginning at P10. Subsequent staining of acutely dissociated- retinal cells confirmed the cellular origin of the signals, which arose from photoreceptor inner segments. The spatial and temporal patterns of retinal vascular development from P0 to P13 were comparable in all genotypes of wild-type, vldlr-/-, and heterozygous mice. However, abnormal vessel sprouts were noticeable in vldlr-/- mice at P14, which continued to grow in depth and protruded into the outer nuclear layer towards subretinal space. By P16, some of these sprouting vascular buds started to expand forming vascular loops without penetrating the RPE layer. Extensive SNVs were evident in subretinal space at P21.
The late onset of VLDLR expression at the end of the second postnatal week in the mouse retina is correlated with later stage of retinal vessel development while forming the two deep layers of capillary beds in the inner and outer plexiform layers. Loss of VLDLR does not affect the early development of retinal vasculature. These data support the conclusion that VLDLR is not required for the early postnatal development of retinal vessels and it may play a role in preventing vessel growth into the subretinal space.
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