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Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model
Author(s) -
Fang Yuan,
Tschulakow Alexander,
Taubitz Tatjana,
Illing Barbara,
Biesemeier Antje,
JulienSchraermeyer Sylvie,
Radu Roxana A.,
Jiang Zhichun,
Schraermeyer Ulrich
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901784rr
Subject(s) - stargardt disease , lipofuscin , autofluorescence , abca4 , retinal pigment epithelium , retinal , retinal degeneration , pathology , fundus (uterus) , biology , macular degeneration , anatomy , ophthalmology , medicine , phenotype , fluorescence , optics , biochemistry , physics , gene
Stargardt disease (STGD1), known as inherited retinal dystrophy, is caused by ABCA4 mutations. The pigmented Abca4 −/− mouse strain only reflects the early stage of STGD1 since it is devoid of retinal degeneration. This blue light‐illuminated pigmented Abca4 −/− mouse model presented retinal pigment epithelium (RPE) and photoreceptor degeneration which was similar to the advanced STGD1 phenotype. In contrast, wild‐type mice showed no RPE degeneration after blue light illumination. In Abca4 −/− mice, the acute blue light diminished the mean autofluorescence (AF) intensity in both fundus short‐wavelength autofluorescence (SW‐AF) and near‐infrared autofluorescence (NIR‐AF) modalities correlating with reduced levels of bisretinoid‐fluorophores. Blue light‐induced RPE cellular damage preceded the photoreceptors loss. In late‐stage STGD1‐like patient and blue light‐illuminated Abca4 −/− mice, lipofuscin and melanolipofuscin granules were found to contribute to NIR‐AF, indicated by the colocalization of lipofuscin‐AF and NIR‐AF under the fluorescence microscope. In this mouse model, the correlation between in vivo and ex vivo assessments revealed histological characteristics of fundus AF abnormalities. The flecks which are hyper AF in both SW‐AF and NIR‐AF corresponded to the subretinal macrophages fully packed with pigment granules (lipofuscin, melanin, and melanolipofuscin). This mouse model, which has the phenotype of advanced STGD1, is important to understand the histopathology of Stargardt disease.