Col4a1 mutations cause progressive retinal neovascular defects and retinopathy

Scientific Reports
Marcel V AlaviDouglas B Gould

Abstract

Mutations in collagen, type IV, alpha 1 (COL4A1), a major component of basement membranes, cause multisystem disorders in humans and mice. In the eye, these include anterior segment dysgenesis, optic nerve hypoplasia and retinal vascular tortuosity. Here we investigate the retinal pathology in mice carrying dominant-negative Col4a1 mutations. To this end, we examined retinas longitudinally in vivo using fluorescein angiography, funduscopy and optical coherence tomography. We assessed retinal function by electroretinography and studied the retinal ultrastructural pathology. Retinal examinations revealed serous chorioretinopathy, retinal hemorrhages, fibrosis or signs of pathogenic angiogenesis with chorioretinal anastomosis in up to approximately 90% of Col4a1 mutant eyes depending on age and the specific mutation. To identify the cell-type responsible for pathogenesis we generated a conditional Col4a1 mutation and determined that primary vascular defects underlie Col4a1-associated retinopathy. We also found focal activation of Müller cells and increased expression of pro-angiogenic factors in retinas from Col4a1(+/Δex41)mice. Together, our findings suggest that patients with COL4A1 and COL4A2 mutations may be at elevated risk o...Continue Reading

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Citations

Jan 4, 2017·Matrix Biology : Journal of the International Society for Matrix Biology·Ambra PozziRenato V Iozzo
Oct 31, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Marion Jeanne, Douglas B Gould
Feb 27, 2017·Disease Models & Mechanisms·Mao MaoDouglas B Gould
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Sep 6, 2019·International Journal of Molecular Sciences·Vo Van GiauSang Yun Kim
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Jan 18, 2020·Scientific Reports·Yoshihiro IshikawaHans Peter Bächinger
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Aug 8, 2021·International Journal of Molecular Sciences·Blanca Chinchilla, Rosario Fernandez-Godino
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Methods Mentioned

BETA
light microscopy
transmission electron microscopy
reverse transcription PCR
RAP
PCR

Software Mentioned

Adobe
Photoshop
AxioVision

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