Retinal Histopathology of an XLRP Carrier with a Mutation in the RPGR Exon ORF15

Aguirre, Gustavo D.; Yashar, Beverly M.; John, Sinoj K.; Smith, J. Russell; Breuer, Debra K.; Hiriyanna, Suja; Swaroop, Anand; Milam, Ann H.

doi:10.1006/exer.2002.2037

Cited by 29 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent publication on a donor eye of a carrier of XLRP by Aguirre et al [1] supports the results with 2CT perimetry. The histopathologic studies of the more normal areas of the retina showed atrophic foci in apparent selective preservation of cones relative to rods.…”

Section: Discussionsupporting

confidence: 52%

Fundus autofluorescence in carriers of X-linked recessive retinitis pigmentosa associated with mutations in RPGR, and correlation with electrophysiological and psychophysical data

Wegscheider

Preising

Lorenz

2004

Graefe's Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

AF had a specific pattern in 9 of 11 carriers from two families with mutations in RPGR. The result was independent of the family investigated. The radial pattern may be explained by random X-inactivation early during embryogenesis subsequently preserved in all daughter cells and the centrifugal radial growth pattern of the developing neuroretina. AF may prove to be a rapid and easy clinical test to identify carriers of RP3.

show abstract

Section: Discussionsupporting

confidence: 52%

Fundus autofluorescence in carriers of X-linked recessive retinitis pigmentosa associated with mutations in RPGR, and correlation with electrophysiological and psychophysical data

Wegscheider

Preising

Lorenz

2004

Graefe's Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

show abstract

“…26 The resulting patterns of random X inactivation have been explicitly demonstrated in the retinas of mice 26 , which show mosaic patterns within the retina, random variation in the total amount of retina affected, as well as interocular differences in severity. Mosaic patterns can also be seen in some human XLRP carriers evaluated in vivo with advanced imaging techniques 21 , and in one case, histology of eyes from a human carrier eye showed “patchy” degeneration 36 . In the present study, the observations that the ERG responses were, on average, approximately half the lower limit of normal (dotted lines, Figure 2), and that the mean 30 Hz amplitude rate of decay was half of that of fully affected XLRP males (3.7% vs 7.4%) are remarkably consistent with the Lyon hypothesis of random X-chromosome inactivation.…”

Section: Discussionmentioning

confidence: 96%

Visual Function in Carriers of X-Linked Retinitis Pigmentosa

et al. 2015

View full text Add to dashboard Cite

Purpose To determine the frequency and severity of visual function loss in female carriers of X-linked retinitis pigmentosa (XLRP). Design Case series. Participants XLRP carriers with cross-sectional data (n = 242) and longitudinal data (n = 34, median follow-up: 16 years, follow-up range: 3–37 years). Half of the carriers were from RPGR- or RP2-genotyped families. Methods Retrospective medical records review. Main Outcome Measures Visual acuities, visual field areas, final dark adaptation thresholds, and full-field ERGs to 0.5 Hz and 30 Hz flashes. Results In genotyped families, 40% of carriers showed a baseline abnormality on at least one of the three psychophysical tests. There was a wide range of function among carriers; for example 3 of 121 (2%) of genotyped carriers were legally blind due to poor visual acuity, some as young as 35 years of age. Visual fields were less affected than visual acuity. In all carriers, the average ERG amplitude to 30 Hz flashes was about 50% of normal, and the average exponential rate of amplitude loss over time was half that of XLRP males (3.7%/year vs 7.4%/year, respectively). Among obligate carriers with affected fathers and/or sons, 53 of 55 (96%) had abnormal baseline ERGs. Some carriers who initially had completely normal fundi in both eyes went on to develop moderately decreased vision, though not legal blindness. Among carriers with RPGR mutations, those with mutations in ORF15, compared to those in exons 1–14, had worse final dark adaptation thresholds and lower 0.5 Hz and 30 Hz ERG amplitudes. Conclusions Most carriers of XLRP had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. Carriers of RPGR ORF15 mutations tended to have worse visual function than carriers of RPGR exon 1–14 mutations. Since XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected males, these observations were consistent with the Lyon hypothesis of random X-inactivation.

show abstract

“…Mislocalization of rod and cone opsins is observed in post-mortem eyes from RP3 carriers [52], [53], XLPRA dogs with two different mutations in ORF15 [28], and in two other genetically independent strains of Rpgr -mutant mice [26], [27]. For mice in which Rpgr exon 4 was deleted, genetic background was found to play a major role in determining the extent of rod and cone involvement, with rod disease predominating on the B6 background, and cone disease predominating on the albino BALB/cJ background [27].…”

Section: Discussionmentioning

confidence: 97%

Rd9 Is a Naturally Occurring Mouse Model of a Common Form of Retinitis Pigmentosa Caused by Mutations in RPGR-ORF15

et al. 2012

Self Cite

View full text Add to dashboard Cite

Animal models of human disease are an invaluable component of studies aimed at understanding disease pathogenesis and therapeutic possibilities. Mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR) are the most common cause of X-linked retinitis pigmentosa (XLRP) and are estimated to cause 20% of all retinal dystrophy cases. A majority of RPGR mutations are present in ORF15, the purine-rich terminal exon of the predominant splice-variant expressed in retina. Here we describe the genetic and phenotypic characterization of the retinal degeneration 9 (Rd9) strain of mice, a naturally occurring animal model of XLRP. Rd9 mice were found to carry a 32-base-pair duplication within ORF15 that causes a shift in the reading frame that introduces a premature-stop codon. Rpgr ORF15 transcripts, but not protein, were detected in retinas from Rd9/Y male mice that exhibited retinal pathology, including pigment loss and slowly progressing decrease in outer nuclear layer thickness. The levels of rhodopsin and transducin in rod outer segments were also decreased, and M-cone opsin appeared mislocalized within cone photoreceptors. In addition, electroretinogram (ERG) a- and b-wave amplitudes of both Rd9/Y male and Rd9/Rd9 female mice showed moderate gradual reduction that continued to 24 months of age. The presence of multiple retinal features that correlate with findings in individuals with XLRP identifies Rd9 as a valuable model for use in gaining insight into ORF15-associated disease progression and pathogenesis, as well as accelerating the development and testing of therapeutic strategies for this common form of retinal dystrophy.

show abstract

Retinal Histopathology of an XLRP Carrier with a Mutation in the RPGR Exon ORF15

Cited by 29 publications

References 36 publications

Fundus autofluorescence in carriers of X-linked recessive retinitis pigmentosa associated with mutations in RPGR, and correlation with electrophysiological and psychophysical data

Fundus autofluorescence in carriers of X-linked recessive retinitis pigmentosa associated with mutations in RPGR, and correlation with electrophysiological and psychophysical data

Visual Function in Carriers of X-Linked Retinitis Pigmentosa

Rd9 Is a Naturally Occurring Mouse Model of a Common Form of Retinitis Pigmentosa Caused by Mutations in RPGR-ORF15

Contact Info

Product

Resources

About