Remodeling of the human retina in choroideremia: rab escort protein 1 (REP-1) mutations

Samuel G Jacobson; Artur V Cideciyan; Alexander Sumaroka; Tomas S Aleman; Sharon B Schwartz; Elizabeth A M Windsor; Alejandro J Roman; Edwin M Stone; Ian M MacDonald

doi:10.1167/iovs.06-0424

Back

Remodeling of the human retina in choroideremia: rab escort protein 1 (REP-1) mutations

Journal article

Peer reviewed

Remodeling of the human retina in choroideremia: rab escort protein 1 (REP-1) mutations

Samuel G Jacobson, Artur V Cideciyan, Alexander Sumaroka, Tomas S Aleman, Sharon B Schwartz, Elizabeth A M Windsor, Alejandro J Roman, Edwin M Stone and Ian M MacDonald

Investigative ophthalmology & visual science, Vol.47(9), pp.4113-4120

09/2006

DOI: 10.1167/iovs.06-0424

PMID: 16936131

View Online

Abstract

To characterize in detail the disease expression in choroideremia (CHM), a blinding X-linked disease of the retina caused by loss-of-function mutations in Rab Escort Protein 1 (REP-1). CHM is readily diagnosed in the clinic and by molecular testing but has lacked an animal model to test hypotheses and therapeutics. The recent report of a mouse model for CHM prompts the need for reassessment of the human disease in anticipation of treatment initiatives. CHM hemizygotes with REP-1 mutations, spanning an age range of 7 decades, were studied with in vivo microscopy by optical coherence tomography. The disease expression was complex. Earliest stages involved a thickening of the retina that was otherwise normally laminated. Loss of photoreceptors, either independent or associated with retinal pigment epithelium (RPE) depigmentation, was followed by disorganization and further thickening of the retina with interlaminar bridges. The dysmorphic retina then slowly thinned over decades. Laminopathy occurred first in more peripheral rod-rich regions and later in the cone-rich fovea. The CHM disease sequence involves detectable retinal thickening, which may be due to Müller cell activation and hypertrophy from photoreceptor stress. Photoreceptor degeneration, RPE depigmentation, and retinal remodeling follow. The results represent in vivo evidence in humans for retinal remodeling and provide a marker for the earliest stage of this response to genetic retinal disease. For CHM and other candidate human retinopathies considered for therapy, there is now a framework for making informed decisions about timing, retinal location, and potential value of treatment.

Choroideremia - diagnosis

Tomography, Optical Coherence

Humans

Middle Aged

Male

rab GTP-Binding Proteins - genetics

Psychophysics

Choroideremia - genetics

Adaptor Proteins, Signal Transducing

Alkyl and Aryl Transferases - genetics

Adolescent

Pigment Epithelium of Eye - pathology

Adult

Mutation

Child

Retina - pathology

Hypertrophy

Details

Title: Subtitle: Remodeling of the human retina in choroideremia: rab escort protein 1 (REP-1) mutations
Creators: Samuel G Jacobson - Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. jacobsos@mail.med.upenn.edu
Artur V Cideciyan
Alexander Sumaroka
Tomas S Aleman
Sharon B Schwartz
Elizabeth A M Windsor
Alejandro J Roman
Edwin M Stone
Ian M MacDonald
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.47(9), pp.4113-4120
DOI: 10.1167/iovs.06-0424
PMID: 16936131
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Language: English
Date published: 09/2006
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980024602771

Metrics

32 Record Views

152 Times Cited - Web of Science