Function of MYO7A in the Human RPE and the Validity of Shaker1 Mice as a Model for Usher Syndrome 1B

被引:38
作者
Gibbs, Daniel [2 ]
Diemer, Tanja [1 ,2 ]
Khanobdee, Kornnika [2 ]
Hu, Jane [1 ]
Bok, Dean [1 ,4 ,5 ]
Williams, David S. [1 ,2 ,3 ,4 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA
[2] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA
[4] Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA
基金
美国国家卫生研究院;
关键词
RETINAL-PIGMENT EPITHELIUM; SYNDROME TYPE-I; MYOSIN-VIIA; PHOTORECEPTOR CELLS; MELANOSOME DISTRIBUTION; GENE; MOUSE; MUTATIONS; RAB27A; EXPRESSION;
D O I
10.1167/iovs.09-4032
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. To investigate the function of MYO7A in human RPE cells and to test the validity of using shaker1 RPE in preclinical studies on therapies for Usher syndrome 1B by comparing human and mouse cells. METHODS. MYO7A was localized by immunofluorescence. Primary cultures of human and mouse RPE cells were used to measure melanosome motility and rod outer segment (ROS) phagocytosis and digestion. MYO7A was knocked down in the human RPE cells by RNAi to test for a mutant phenotype in melanosome motility. RESULTS. The distribution of MYO7A in the RPE of human and mouse was found to be comparable, both in vivo and in primary cultures. Primary cultures of human RPE cells phagocytosed and digested ROSs with kinetics comparable to that of primary cultures of mouse RPE cells. Melanosome motility was also comparable, and, after RNAi knockdown, consisted of longer-range fast movements characteristic of melanosomes in shaker1 RPE. CONCLUSIONS. The localization and function of MYO7A in human RPE cells is comparable to that in mouse RPE cells. Although shaker1 retinas do not undergo degeneration, correction of mutant phenotypes in the shaker1 RPE represents a valid preclinical test for potential therapeutic treatments. (Invest Ophthalmol Vis Sci. 2010;51:1130-1135) DOI:10.1167/iovs.09-4032
引用
收藏
页码:1130 / 1135
页数:6
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