[HTML][HTML] Retinal disease in mice lacking hypoxia-inducible transcription factor-2α
K Ding, M Scortegagna, R Seaman… - … & visual science, 2005 - iovs.arvojournals.org
K Ding, M Scortegagna, R Seaman, DG Birch, JA Garcia
Investigative ophthalmology & visual science, 2005•iovs.arvojournals.orgmethods. Histologic, electroretinographic (ERG), and molecular studies were performed on
samples obtained from age-and gender-matched HIF-2α-null (HIF-2α-KO), HIF-2α-
heterozygous (HIF-2α-HET), and wild-type (WT) littermate mice. results. HIF-2α-KO mice
exhibited marked thinning of the retina and abnormal retinal vasculature. The pathologic
changes in HIF-2α-KO mice were associated with a virtual absence of postreceptor function.
The expression of a surrogate marker for HIF-2α mRNA localized to vascular endothelial …
samples obtained from age-and gender-matched HIF-2α-null (HIF-2α-KO), HIF-2α-
heterozygous (HIF-2α-HET), and wild-type (WT) littermate mice. results. HIF-2α-KO mice
exhibited marked thinning of the retina and abnormal retinal vasculature. The pathologic
changes in HIF-2α-KO mice were associated with a virtual absence of postreceptor function.
The expression of a surrogate marker for HIF-2α mRNA localized to vascular endothelial …
methods. Histologic, electroretinographic (ERG), and molecular studies were performed on samples obtained from age-and gender-matched HIF-2α-null (HIF-2α-KO), HIF-2α-heterozygous (HIF-2α-HET), and wild-type (WT) littermate mice.
results. HIF-2α-KO mice exhibited marked thinning of the retina and abnormal retinal vasculature. The pathologic changes in HIF-2α-KO mice were associated with a virtual absence of postreceptor function. The expression of a surrogate marker for HIF-2α mRNA localized to vascular endothelial, amacrine, and retinal pigment epithelial (RPE) cells. Several HIF-2α target genes involved in angiogenesis, retinal protection, and stress responses have altered expression patterns in HIF-2α-KO retinas.
conclusions. HIF-2α-KO mice exhibit marked retinopathy consistent with complete loss of vision by 1 month of age. Impaired HIF-2α signaling in HIF-2α-KO mice likely produces functional deficits in cell types in which HIF-2α 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-2α-KO mice.
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