@article {603931, title = {Retinal Dystrophy and Optic Nerve Pathology in the Mouse Model of Mucolipidosis IV.}, journal = {Am J Pathol}, volume = {186}, number = {1}, year = {2016}, month = {2016 Jan}, pages = {199-209}, 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.}, issn = {1525-2191}, doi = {10.1016/j.ajpath.2015.09.017}, author = {Grishchuk, Yulia and Stember, Katherine G and Matsunaga, Aya and Olivares, Ana M and Cruz, Nelly M and King, Victoria E and Humphrey, Daniel M and Wang, Shirley L and Muzikansky, Alona and Betensky, Rebecca A and Thoreson, Wallace B and Haider, Neena and Slaugenhaupt, Susan A} }