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Cited by 250Retinal Development and DisordersCellular transport and secretionRetinal Diseases and Treatments

Abnormal phagocytosis by retinal pigmented epithelium that lacks myosin VIIa, the Usher syndrome 1B protein.

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Gibbs, Daniel, Kitamoto, Junko, Williams, David S.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1130432100PMC PMC164472
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Abstract

Mutations in the myosin VIIa gene (MYO7A) cause Usher syndrome type 1B (USH1B), a major type of the deaf-blind disorder, Usher syndrome. We have studied mutant phenotypes in the retinas of Myo7a mutant mice (shaker1), with the aim of elucidating the role(s) of myosin VIIa in the retina and what might underlie photoreceptor degeneration in USH1B patients. A photoreceptor defect has been described. Here, we report that the phagocytosis of photoreceptor outer segment disks by the retinal pigment epithelium (RPE) is abnormal in Myo7a null mice. Both in vivo and in primary cultures of RPE cells, the transport of ingested disks out of the apical region is inhibited in the absence of Myo7a. The results with the cultured RPE cells were the same, irrespective of whether the disks came from wild-type or mutant mice, thus demonstrating that the RPE is the source of this defect. The inhibited transport seems to delay phagosome-lysosomal fusion, as the degradation of ingested disks was slower in mutant RPE. Moreover, fewer packets of disk membranes were ingested in vivo, possibly because retarded removal of phagosomes from the apical processes inhibited the ingestion of additional disk membranes. We conclude that Myo7a is required for the normal processing of ingested disk membranes in the RPE, primarily in the basal transport of phagosomes into the cell body where they then fuse with lysosomes. Because the phagocytosis of photoreceptor disks by the RPE has been shown to be critical for photoreceptor cell viability, this defect likely contributes to the progressive blindness in USH1B.

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Authors
Gibbs, D., Kitamoto, J., & Williams, D. S.
Affiliations
University of California San Diego (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-05-12
Volume
100
Issue
11
Pages
6481-6486
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1130432100
PMC
PMC164472
OpenAlex
W2082211576
Cited by
250
References
54
Citations by year
2026: 7 · 2025: 2 · 2024: 11 · 2023: 9 · 2022: 14 · 2021: 9 · 2020: 12 · 2019: 7 · 2018: 14 · 2017: 12 · 2016: 7 · 2015: 16 · 2014: 19 · 2013: 14 · 2012: 6
FWCI
3.68
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p30ey012598-05)
  • National Eye Institute (P30-EY012598, EY 12598, R01EY007042, EY07042)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
MYO7A, Usher syndrome type 1B, retinal pigment epithelium, phagocytosis, phagosome-lysosome fusion, photoreceptor degeneration, deafblindness, lysosomal trafficking
MeSH terms
Myosin VIIa, Animals, Cells, Cultured, Dyneins, Mice, Inbred BALB C, Myosins, Phagocytosis, Pigment Epithelium of Eye, Reactive Oxygen Species, Mice

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