Retinal disease in mice lacking hypoxia-inducible transcription factor-2α

被引:29
作者
Ding, K
Scortegagna, M
Seaman, R
Birch, DG
Garcia, JA
机构
[1] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX 75390 USA
[3] Retina Fdn SW, Dallas, TX USA
关键词
D O I
10.1167/iovs.04-0788
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. To characterize ocular disease in HIF-2alpha-null mice. METHODS. Histologic, electroretinographic (ERG), and molecular studies were performed on samples obtained from age- and gender-matched HIF-2alpha-null (HIF-2alpha-KO), HIF-2alpha-heterozygous (HIF-2alpha-HET), and wild-type (WT) littermate mice. RESULTS. HIF-2alpha-KO mice exhibited marked thinning of the retina and abnormal retinal vasculature. The pathologic changes in HIF-2alpha-KO mice were associated with a virtual absence of postreceptor function. The expression of a surrogate marker for HIF-2alpha mRNA localized to vascular endothelial, amacrine, and retinal pigment epithelial (RPE) cells. Several HIF-2alpha target genes involved in angiogenesis, retinal protection, and stress responses have altered expression patterns in HIF-2alpha-KO retinas. CONCLUSIONS. HIF-2alpha-KO mice exhibit marked retinopathy consistent with complete loss of vision by 1 month of age. Impaired HIF-2alpha signaling in HIF-2alpha-KO mice likely produces functional deficits in cell types in which HIF-2alpha normally is expressed, ultimately resulting in retinopathy. Future studies will address whether the molecular abnormalities described in this study are directly responsible for the retinal disease in HIF-2alpha-KO mice.
引用
收藏
页码:1010 / 1016
页数:7
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