Dataset Information

Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV.

ABSTRACT: Mucolipidosis IV is a debilitating developmental lysosomal storage disorder characterized by severe neuromotor retardation and progressive loss of vision, leading to blindness by the second decade of life. Mucolipidosis IV is caused by loss-of-function mutations in the MCOLN1 gene, which encodes the transient receptor potential channel protein mucolipin-1. Ophthalmic pathology in patients includes corneal haze and progressive retinal and optic nerve atrophy. Herein, we report ocular pathology in Mcoln1(-/-) mouse, a good phenotypic model of the disease. Early, but non-progressive, thinning of the photoreceptor layer, reduced levels of rhodopsin, disrupted rod outer segments, and widespread accumulation of the typical storage inclusion bodies were the major histological findings in the Mcoln1(-/-) retina. Electroretinograms showed significantly decreased functional response (scotopic a- and b-wave amplitudes) in the Mcoln1(-/-) mice. At the ultrastructural level, we observed formation of axonal spheroids and decreased density of axons in the optic nerve of the aged (6-month-old) Mcoln1(-/-) mice, which indicates progressive axonal degeneration. Our data suggest that mucolipin-1 plays a role in postnatal development of photoreceptors and provides a set of outcome measures that can be used for ocular therapy development for mucolipidosis IV.

SUBMITTER: Grishchuk Y

PROVIDER: S-EPMC4715222 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV.

Grishchuk Yulia Y Stember Katherine G KG Matsunaga Aya A Olivares Ana M AM Cruz Nelly M NM King Victoria E VE Humphrey Daniel M DM Wang Shirley L SL Muzikansky Alona A Betensky Rebecca A RA Thoreson Wallace B WB Haider Neena N Slaugenhaupt Susan A SA

The American journal of pathology 20151120 1

Mucolipidosis IV is a debilitating developmental lysosomal storage disorder characterized by severe neuromotor retardation and progressive loss of vision, leading to blindness by the second decade of life. Mucolipidosis IV is caused by loss-of-function mutations in the MCOLN1 gene, which encodes the transient receptor potential channel protein mucolipin-1. Ophthalmic pathology in patients includes corneal haze and progressive retinal and optic nerve atrophy. Herein, we report ocular pathology in ...[more]

PMID: 26608452

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Dataset Information

Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV.

Publications

Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV.

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