Fzd4 Haploinsufficiency Delays Retinal Revascularization in the Mouse Model of Oxygen Induced Retinopathy
| Autor: | Johane M Robitaille, Michael H. Ngo, Joanna Borowska-Fielding, Sara Nejat, Christopher R. McMaster, Melanie E. M. Kelly, Godfrey Heathcote |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cardiovascular Procedures medicine.medical_treatment lcsh:Medicine Haploinsufficiency Retinal Neovascularization Mice chemistry.chemical_compound 0302 clinical medicine Medicine and Health Sciences lcsh:Science Multidisciplinary Retinopathy of prematurity Animal Models medicine.anatomical_structure Oxygen-Induced Retinopathy Optic nerve Retinal Disorders Female Anatomy Research Article Retinopathy Computer and Information Sciences medicine.medical_specialty Genotype Ocular Anatomy Mouse Models Surgical and Invasive Medical Procedures Research and Analysis Methods Revascularization Retina Computer Software 03 medical and health sciences Model Organisms Ocular System Ophthalmology medicine Animals Retinopathy of Prematurity business.industry lcsh:R Biology and Life Sciences Retinal Vessels Optic Nerve Retinal medicine.disease Frizzled Receptors eye diseases Surgery Oxygen Disease Models Animal 030104 developmental biology Microscopy Fluorescence chemistry Cardiovascular Anatomy 030221 ophthalmology & optometry Familial exudative vitreoretinopathy Blood Vessels lcsh:Q sense organs business |
| Zdroj: | PLoS ONE, Vol 11, Iss 8, p e0158320 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Mutations in genes that code for components of the Norrin-FZD4 ligand-receptor complex cause the inherited childhood blinding disorder familial exudative vitreoretinopathy (FEVR). Statistical evidence from studies of patients at risk for the acquired disease retinopathy of prematurity (ROP) suggest that rare polymorphisms in these same genes increase the risk of developing severe ROP, implying that decreased Norrin-FZD4 activity predisposes patients to more severe ROP. To test this hypothesis, we measured the development and recovery of retinopathy in wild type and Fzd4 heterozygous mice in the absence or presence of ocular ischemic retinopathy (OIR) treatment. Avascular and total retinal vascular areas and patterning were determined, and vessel number and caliber were quantified. In room air, there was a small delay in retinal vascularization in Fzd4 heterozygous mice that resolved as mice reached maturity suggestive of a slight defect in retinal vascular development. Subsequent to OIR treatment there was no difference between wild type and Fzd4 heterozygous mice in the vaso-obliterated area following exposure to high oxygen. Importantly, after return of Fzd4 heterozygous mice to room air subsequent to OIR treatment, there was a substantial delay in retinal revascularization of the avascular area surrounding the optic nerve, as well as delayed vascularization toward the periphery of the retina. Our study demonstrates that a small decrease in Norrin-Fzd4 dependent retinal vascular development lengthens the period during which complications from OIR could occur. |
| Databáze: | OpenAIRE |
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