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http://purl.uniprot.org/citations/28622396http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28622396http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

The mutation R345W in EFEMP1 (fibulin-3) causes macular degeneration. This study sought to determine whether proteoglycan content and diffusion across Bruch's membrane are altered in Efemp1ki/ki mice carrying this mutation or in Efemp1-/-mice.

Methods

Proteoglycans in mouse Bruch's membranes were stained with Cupromeronic Blue (CB). Heparan sulfated proteoglycan (HSPG) and chondroitin/dermatan sulfate proteoglycan (C/DSPG) distributions were visualized following treatments with chondroitinase ABC (C-ABC) or nitrous acid. Total sulfated glycosaminoglycans (sGAGs) in Bruch's membrane/choroid (BrM/Ch) were measured with dimethylmethylene blue (DMMB). Matrix metalloprotease (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-3 were examined by immunofluorescence and quantified using Image J. Molecules with different Stokes radius (Rs) were allowed simultaneously to diffuse through mouse BrM/Ch mounted in a modified Ussing chamber. Samples were quantified using gel exclusion chromatography.

Results

HSPGs and C/DSPGs were markedly increased in Efemp1ki/ki Bruch's membrane, and MMP-2 and MMP-9 were decreased, but TIMP-3 was increased. Diffusion across Efemp1ki/ki Bruch's membrane was impaired. In contrast, the proteoglycan amount in Efemp1-/-Bruch's membrane was not significantly different, but the size of proteoglycans was much larger. MMP-2, MMP-3, and TIMP-3 levels were similar to that of Efemp1+/+ mice, but they were localized diffusely in retinal pigment epithelium (RPE) cells instead of Bruch's membrane. Diffusion across Efemp1-/-Bruch's membrane was enhanced.

Conclusions

Mutant fibulin-3 causes proteoglycan accumulation, reduction of MMP-2 and MMP-9, but increase of TIMP-3, and impairs diffusion across Bruch's membrane. Fibulin-3 ablation results in altered sizes of proteoglycans, altered distributions of MMP-2, MMP-9, and TIMP-3, and enhances diffusion across Bruch's membrane."xsd:string
http://purl.uniprot.org/citations/28622396http://purl.org/dc/terms/identifier"doi:10.1167/iovs.17-21720"xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/author"Cross S.D."xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/author"Marmorstein A.D."xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/author"Marmorstein L.Y."xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/author"Stanton J.B."xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/author"Zayas-Santiago A."xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/name"Invest Ophthalmol Vis Sci"xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/pages"3046-3054"xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/title"Mutant Fibulin-3 Causes Proteoglycan Accumulation and Impaired Diffusion Across Bruch's Membrane."xsd:string
http://purl.uniprot.org/citations/28622396http://purl.uniprot.org/core/volume"58"xsd:string
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