Heckenlively John R, Hawes Norman L, Friedlander Martin, Nusinowitz Steven, Hurd Ronald, Davisson Muriel, Chang Bo
Jules Stein Eye Institute, UCLA School of Medicine, University of California at Los Angeles, 100 Stein Plaza, Los Angeles, CA 90095, USA.
Retina. 2003 Aug;23(4):518-22. doi: 10.1097/00006982-200308000-00012.
To characterize the phenotype and report a reliable genetic model of retinal angiogenesis and subretinal neovascularization in the mouse.
The mouse phenotype was characterized using ophthalmoscopy, fundus photography, fluorescein angiography, electroretinography, histology, gene sequencing, and linkage analysis.
Scattered pink-gray retinal lesions were found on ophthalmoscopy and were confirmed to be subretinal neovascularization on fluorescein angiography. On histologic examination, outer plexiform retinal neovascularization with growth into the subretinal space was found as early as postnatal Day 15. On genetic analysis, homozygosity of the Vldlr mutation always segregated with the retinal angiogenesis, whereas normal and heterozygous mice had no neovascularization. The histologic studies 15 to 18 days consistently showed new outer plexiform neovascular vessels drawn to the subretinal space by 20 days, and by 30 to 50 days, subretinal hemorrhages and choroidal anastomoses were common. Mice by 8 months had increased vascularity of the iris and ciliary body.
The Vldlr mutation in the mouse provides a good model for retinal angiogenesis and subretinal neovascularization. Finding a strong association between retinal angiogenesis and a very low density lipid receptor mutation is new, and study of lipid receptor physiology may broaden the understanding of retinal angiogenesis.
描述小鼠视网膜血管生成和视网膜下新生血管形成的表型，并报告一种可靠的遗传模型。
使用检眼镜检查、眼底照相、荧光素血管造影、视网膜电图、组织学、基因测序和连锁分析来描述小鼠表型。
检眼镜检查发现散在的粉灰色视网膜病变，荧光素血管造影证实为视网膜下新生血管形成。组织学检查发现，早在出生后第15天就有外层视网膜神经丛新生血管生长至视网膜下间隙。基因分析显示，Vldlr突变的纯合子总是与视网膜血管生成相关，而正常和杂合小鼠没有新生血管形成。15至18天的组织学研究持续显示，到20天时新的外层视网膜神经丛新生血管被吸引至视网膜下间隙，到30至50天时，视网膜下出血和脉络膜吻合很常见。8个月大的小鼠虹膜和睫状体血管增多。
小鼠中的Vldlr突变提供了一个研究视网膜血管生成和视网膜下新生血管形成的良好模型。发现视网膜血管生成与极低密度脂蛋白受体突变之间存在强关联是新的发现，对脂质受体生理学的研究可能会拓宽对视网膜血管生成的理解。
