Retinal Pigment Epithelium Defects in Humans and Mice with Mutations in MYO7A : Imaging Melanosome-Specific Autofluorescence
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PURPOSE: Usher syndrome (USH) is a genetically heterogeneous disease with autosomal recessive deafness and blindness. Gene therapy is under development for use in the most common genetic variant of USH1, USH1B, which is caused by mutations in the MYO7A gene. This study was undertaken to identify an imaging method for noninvasively monitoring the RPE component of the USH1B disease. METHODS: NIR-autofluorescence (NIR-AF) was examined in USH1B patients with scanning laser ophthalmoscopy, and retinal thickness with spectral-domain optical coherence tomography. Myo7a-null mouse retinas and purified RPE melanosomes were analyzed by spectral deconvolution confocal microscopy. RESULTS: In USH1B patients, NIR-AF was normal in regions of retained photoreceptors and abnormal in regions lacking photoreceptors. Subtle changes in NIR-AF were associated with intermediate photoreceptor loss. In ex vivo mouse retinas, the NIR-AF source was traced to the melanosomes in the RPE and choroid. Purified RPE melanosomes emitted the same signal. Fluorophores, excited by long-wavelength light, were evident throughout the apical RPE of WT mouse eyecups. In Myo7a-null eyecups, these fluorophores had a more restricted distribution. They were absent from the apical processes of the RPE, thus correlating with the melanosome localization defects described previously by conventional microscopy. CONCLUSIONS: The data indicate that melanosomes in the RPE and choroid are the dominant source of NIR-AF from the posterior region of the eye. NIR-AF is a novel tool that provides sensitive and label-free imaging of the retina and RPE and is currently the only melanosome-specific, noninvasive technique for monitoring RPE disease in new therapeutic initiatives for retinal degenerations.
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Melanosomes are the dominant source of autofluorescence when imaging the posterior region of the eye with near-infrared excitation.
“Melanosomes are the dominant source of autofluorescence, when imaging the posterior region of the eye with near-infrared excitation (Gibbs et al., 2009).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Gibbs et al., 2009
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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
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- Authors
- Gibbs, D., Cideciyan, A. V., Jacobson, S. G., & Williams, D. S.
- Affiliations
- University of California San Diego (US)
- University of Pennsylvania (US)
- Corresponding author
- Gibbs, Daniel
- Williams, David S.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2009-09-01
- Volume
- 50
- Issue
- 9
- Pages
- 4386
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC2884175
- OpenAlex
- W2023768917
- Cited by
- 82
- References
- 57
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 8 · 2014: 3 · 2013: 8 · 2012: 8
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of California, San Diego
- National Eye Institute (EY-13203, R01EY013203, R01EY007042, EY07042)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- Usher syndrome type 1B, retinal pigment epithelium, melanosomes, near-infrared autofluorescence, photoreceptor loss, retinal degeneration, choroid, gene therapy monitoring
- MeSH terms
- Myosin VIIa, Animals, Child, Choroid, Diagnostic Imaging, Disease Models, Animal, Fluorescence, Humans, Mice, Inbred C57BL, Middle Aged, Mutation, Myosins, Ophthalmoscopy, Microscopy, Confocal, Melanosomes, Tomography, Optical Coherence, Mice, Usher Syndromes, Retinal Pigment Epithelium, Young Adult
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