March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
X-linked RP Caused by RPGR Mutations: Natural History of the Human Disease and an Rpgr-mutant Rodent Model
Author Affiliations & Notes
  • Wei Chieh Huang
    Ophthalmology, Scheie Eye Institute,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • Alejandro J. Roman
    Ophthalmology, Scheie Eye Institute,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • Artur V. Cideciyan
    Ophthalmology, Scheie Eye Institute,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • Dina Y. Gewaily
    Ophthalmology, Scheie Eye Institute,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • Maria P. Limberis
    Pathology & Laboratory Medicine,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • Peter Bell
    Pathology & Laboratory Medicine,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • James W. Wilson
    Pathology & Laboratory Medicine,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • Alan F. Wright
    MRC Human Genetics Unit, Edinburgh, United Kingdom
  • Anand Swaroop
    Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, Bethesda, Maryland
  • Samuel G. Jacobson
    Ophthalmology, Scheie Eye Institute,
    University of Pennsylvania, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  Wei Chieh Huang, None; Alejandro J. Roman, None; Artur V. Cideciyan, None; Dina Y. Gewaily, None; Maria P. Limberis, None; Peter Bell, None; James W. Wilson, None; Alan F. Wright, None; Anand Swaroop, None; Samuel G. Jacobson, None
  • Footnotes
    Support  Macula Vision Research Foundation, Hope for Vision, Chatlos Foundation, RPB, NEI intramural program.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2591. doi:
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      Wei Chieh Huang, Alejandro J. Roman, Artur V. Cideciyan, Dina Y. Gewaily, Maria P. Limberis, Peter Bell, James W. Wilson, Alan F. Wright, Anand Swaroop, Samuel G. Jacobson; X-linked RP Caused by RPGR Mutations: Natural History of the Human Disease and an Rpgr-mutant Rodent Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2591.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To investigate the retinal disease due to mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene in human patients and a mouse model.

Methods: : XLRP patients with RPGR mutations (n=20; ages at first visit 8-39 yrs) were followed longitudinally with clinical examinations and rod (R) and cone (C) perimetry. Rpgr-ko mice (ages 4-13 mos) were studied with SD-OCT and electroretinography (ERG). Matched controls were compared with the mutants. A subset of mice had retinal histopathology.

Results: : Different patterns of rod and cone dysfunction were present in the youngest patients studied (8-12 yrs). There could be detectable central R and C sensitivity, midperipheral losses, with or without peripheral R and C islands; C-only central function, midperipheral losses, and peripheral R and C function; or C-only function across the field. Over years to decades, these patterns could progress to C-only central islands without peripheral function. Less commonly, patients had central R and C scotomas but preserved, albeit abnormal, peripheral R and C function. Rpgr-ko mice had R and C ERGs that were reduced at all ages studied. At central and inferior retinal regions, mean ONL thickness was reduced by as much as 15% at 5 mos and thinned to ~50% of controls by 13 mos. Superior retina had relatively slower degeneration. There were disorganized photoreceptor inner and outer segments (IS/OS) at all stages studied.

Conclusions: : RPGR mutations lead to major and progressive loss of rod and cone vision in human XLRP but show different patterns of residual photoreceptor disease expression. Rpgr-ko mice showed onset of degeneration at young ages and progressive rod and cone disease, as in the patients. From these results, ages for pre-clinical treatment in this model can be determined and realistic approaches to human therapy devised.

Keywords: retinal degenerations: hereditary • retina • imaging/image analysis: non-clinical 
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