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Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2005 Sep; Vol. 46 (9), pp. 3372-82. - Publication Year :
- 2005
-
Abstract
- Purpose: To characterize developmental defects and the time course of Norrie disease in retinal and hyaloid vasculature during retinal development and to identify underlying molecular angiogenic pathways that may be affected in Norrie disease, exudative vitreoretinopathy, retinopathy of prematurity, and Coats' disease.<br />Methods: Norrie disease pseudoglioma homologue (Ndph)-knockout mice were studied during retinal development at early postnatal (p) stages (p5, p10, p15, and p21). Histologic techniques, quantitative RT-PCR, ELISA, and Western blot analyses provided molecular data, and scanning laser ophthalmoscopy (SLO) angiography and electroretinography (ERG) were used to obtain in vivo data.<br />Results: The data showed that regression of the hyaloid vasculature of Ndph-knockout mice occurred but was drastically delayed. The development of the superficial retinal vasculature was strongly delayed, whereas the deep retinal vasculature did not form because of the blockage of vessel outgrowth into the deep retinal layers. Subsequently, microaneurysm-like lesions formed. Several angiogenic factors were differentially transcribed during retinal development. Increased levels of hypoxia inducible factor-1alpha (HIF1alpha) and VEGFA, as well as a characteristic ERG pattern, confirmed hypoxic conditions in the inner retina of the Ndph-knockout mouse.<br />Conclusions: These data provide evidence for a crucial role of Norrin in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the development of the deep retinal capillary networks. They also suggest an early and a late phase of Norrie disease and may provide an explanation for similar phenotypic features of allelic retinal diseases in mice and patients as secondary consequences of pathologic hypoxia.
- Subjects :
- Animals
Blotting, Western
DNA-Binding Proteins metabolism
Electroretinography
Enzyme-Linked Immunosorbent Assay
Fluorescein Angiography
Gene Expression physiology
Humans
Hypoxia metabolism
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Infant, Newborn
Mice
Mice, Knockout
Nuclear Proteins metabolism
Ophthalmoscopy
Retinal Neovascularization pathology
Retinal Vessels pathology
Retinopathy of Prematurity pathology
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors metabolism
Vascular Endothelial Growth Factor A metabolism
Vitreoretinopathy, Proliferative pathology
Eye Proteins physiology
Nerve Tissue Proteins physiology
Ophthalmic Artery physiopathology
Retinal Neovascularization metabolism
Retinal Vessels growth & development
Retinopathy of Prematurity metabolism
Vitreoretinopathy, Proliferative metabolism
Vitreous Body blood supply
Subjects
Details
- Language :
- English
- ISSN :
- 0146-0404
- Volume :
- 46
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 16123442
- Full Text :
- https://doi.org/10.1167/iovs.05-0174