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THE PHYSIOLOGY OF THE RETINAL PIGMENT EPITHELIUM IN DANON DISEASE

Thompson, Dorothy A. PhD; Constable, Paul A. PhD; Liasis, Alki PhD; Walters, Bronwen BSc; Esteban, Maite Tome MD

doi: 10.1097/IAE.0000000000000736
Original Study
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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.

Disrupted autophagy associated with LAMP-2 mutations in Danon disease causes an abnormally low transepithelial potential across the retinal pigment epithelium, in both light and darkness, probably because of alterations in tight junction resistance of retinal pigment epithelial cells.

*Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children, London, United Kingdom;

Applied Vision Research Centre, City University London, London, United Kingdom; and

Cardiology, Great Ormond Street Hospital and University College London Heart Hospital, London, United Kingdom.

Reprint requests: Dorothy A. Thompson, PhD, Department of Ophthalmology, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, United Kingdom; e-mail: dorothy.thompson@gosh.nhs.uk

Presented as an oral paper at the International Society for the Clinical Electrophysiology of Vison (ISCEV) Symposium July 2014, Boston, MA.

None of the authors have any financial/conflicting interests to disclose.

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© 2016 by Ophthalmic Communications Society, Inc.