RPGR-associated retinal degeneration in human X-linked RP and a murine model

Wei Chieh Huang, Alan F Wright, Alejandro J Roman, Artur V Cideciyan, Forbes D Manson, Dina Y Gewaily, Sharon B Schwartz, Sam Sadigh, Maria P Limberis, Peter Bell, James M Wilson, Anand Swaroop, Samuel G Jacobson

Research output: Contribution to journalArticlepeer-review


PURPOSE: We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model.

METHODS: XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5-72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset.

RESULTS: Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. CONCLUSIONS: RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy.
Original languageEnglish
Pages (from-to)5594-608
Number of pages15
JournalInvestigative Ophthalmology & Visual Science (IOVS)
Issue number9
Publication statusPublished - 2012


  • Adolescent
  • Adult
  • Aged
  • Animals
  • Child
  • Child, Preschool
  • Disease Models, Animal
  • Eye Proteins
  • Female
  • Genetic Diseases, X-Linked
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Mutation
  • Retinal Cone Photoreceptor Cells
  • Retinal Degeneration
  • Retinal Rod Photoreceptor Cells
  • Retinitis Pigmentosa
  • Visual Acuity
  • Young Adult


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