The physiology of the retinal pigment epithelium in Danon disease
Abstract
PURPOSE: Danon disease is caused by mutations in the lysosome-associated membrane protein-2 gene (LAMP2). In the eye, LAMP2 is expressed only in the retinal pigment epithelium. This study aimed to investigate the previously unreported impact of LAMP2 mutations on the electrooculogram generated by the retinal pigment epithelium. METHODS: Four members of a family with Danon disease were examined. All have mutations in c294G > A, of the LAMP2 gene on Xq24, by which no, or aberrant, protein will be formed. Electrooculograms to International Society for the Clinical Electrophysiology of Vision (ISCEV) standards were recorded with full-field electroretinography, Goldmann kinetic visual fields, and spectral optical coherence tomography with fundus autofluorescence imaging. RESULTS: Electrooculogram amplitude ratios of light rise:dark trough, the Arden index, fell at low-normal limits (range: 1.68-3.94) but misrepresent retinal pigment epithelium health, because the absolute dark trough voltages were abnormally low (median: 140 μV, range: 72-192 μV) as were the light rise amplitudes (median: 297 μV, range: 198-366 μV), and full-field electroretinograms were normal. Hyperfundus autofluorescence and hypofundus autofluorescence changes became more confluent and florid with increasing age of female patients. Goldmann visual field testing showed constriction of the central field. CONCLUSION: Low electrooculogram voltages indicate that the retinal pigment epithelium is unable to maintain its tight junctions in Danon disease.
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Patients with Danon disease have increased fundus autofluorescence and abnormal full-field ERGs, indicative of decreased lysosome function and loss of RPE function.
“Patients with Danon disease have increased fundus autofluorescence and abnormal full-field ERGs, indicative of decreased lysosome function and loss of RPE function (Thompson et al., 2016).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Thompson et al., 2016
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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
- Thompson, D. A., Constable, P. A., Liasis, A., Walters, B., & Esteban, M. T.
- Affiliations
- City, University of London (GB)
- Venue
- Retina
- Published
- 2016-03
- Volume
- 36
- Issue
- 3
- Pages
- 629-638
- ISSN
- 0275-004X (ISSN-L)
- OpenAlex
- W2323603734
- Cited by
- 31
- References
- 49
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 2
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Retina (publishedVersion)
- PubMed (publishedVersion)
- 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 › Physiology › Lysosomal Storage Disorders Research
- Keywords
- Danon disease, retinal pigment epithelium, electrooculogram, fundus autofluorescence, lysosomal storage disease, full-field electroretinography, visual field constriction, X-linked inheritance
- MeSH terms
- Adolescent, Child, Electrooculography, Electroretinography, Female, Humans, Male, Membrane Potentials, Middle Aged, Pedigree, Retinal Diseases, Visual Acuity, Visual Fields, Tight Junctions, Polymorphism, Single Nucleotide, Tomography, Optical Coherence, Lysosomal-Associated Membrane Protein 2, Glycogen Storage Disease Type IIb, Retinal Pigment Epithelium, Young Adult
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