Acid Ceramidase Deficiency in Mice Leads to Severe Ocular Pathology and Visual Impairment

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00077684" target="_blank" >RIV/00023001:_____/19:00077684 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10396325

Result on the web

<a href="https://ajp.amjpathol.org/article/S0002-9440(18)30504-2/fulltext" target="_blank" >https://ajp.amjpathol.org/article/S0002-9440(18)30504-2/fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ajpath.2018.10.018" target="_blank" >10.1016/j.ajpath.2018.10.018</a>

Result language

angličtina

Original language name

Acid Ceramidase Deficiency in Mice Leads to Severe Ocular Pathology and Visual Impairment

Original language description

Farber disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene, resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. In classic cases, patients develop hepatosplenomegaly, nervous system involvement, and childhood mortality. Ocular manifestations include decreased vision, a grayish appearance to the retina with a cherry red spot, and nystagmus. That said, the full effect of ACDase deficiency on the visual system has not been studied in detail. We previously developed a mouse model that is orthologous for a known patient mutation in Asah1 that recapitulates human FD. Herein, we report evidence of a severe ocular pathology in Asah1(P361R/P361R) mice. Asah1(P361R/P361R) mice exhibit progressive retinal and optic nerve pathology. Through noninvasive ocular imaging and histopathological analyses of these Asah1(P361R/P361R) animals, we revealed progressive inflammation, the presence of retinal dysplasia, and significant storage pathology in various cell types in both the retina and optic nerves. Lipidomic analyses of retinal tissues revealed an abnormal accumulation of ceramides and other sphingolipids. Electroretinograms and behavioral tests showed decreased retinal and visual responses. Taken together, these data suggest that ACDase deficiency leads to sphingolipid imbalance, inflammation, dysmorphic retinal and optic nerve pathology, and severe visual impairment.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30109 - Pathology

Project

<a href="/en/project/LM2015091" target="_blank" >LM2015091: National Center for Medical Genomic</a><br>

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

American journal of pathology

ISSN

0002-9440

e-ISSN

—

Volume of the periodical

189

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

19

Pages from-to

320-338

UT code for WoS article

000458713400011

EID of the result in the Scopus database

2-s2.0-85060099082