title: THE PHYSIOLOGY OF THE RETINAL PIGMENT EPITHELIUM IN DANON DISEASE.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Low electrooculogram voltages indicate that the retinal pigment epithelium is unable to maintain its tight junctions in Danon disease.
authors.affiliation: *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.
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Thompson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Constable
authors.forename: Alki
authors.initials: A
authors.lastname: Liasis
authors.forename: Bronwen
authors.initials: B
authors.lastname: Walters
authors.forename: Maite Tome
authors.initials: MT
authors.lastname: Esteban
mesh_terms: D000293:Adolescent; D002648:Child; D004585:Electrooculography; D004596:Electroretinography; D005260:Female; D052120:Glycogen Storage Disease Type IIb / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012164:Retinal Diseases / Q000235:genetics / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000502:physiology*; D019108:Tight Junctions; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2