Retinal Histopathology of a Carrier of X-chromosome-linked Retinitis Pigmentosa

Szamier, R. Bruce; Berson, Eliot L.

doi:10.1016/s0161-6420(85)34044-7

Cited by 33 publications

(29 citation statements)

References 19 publications

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“…As a result of random X-inactivation (also called lyonization), heterozygous female dogs undergo a patchy form of retinal degeneration (Zeiss et al 1999;Beltran et al 2009) that is the result of loss of photoreceptors that are clonally derived from a progenitor cell expressing the mutant XLPRA1 allele. This mosaic pattern of retinal degeneration, which is histologically detectable at 1.4 yr and is still apparent in 7.8-yr-old dogs, resembles the phenotype reported in human XLRP carriers (Szamier and Berson 1985;Jacobson et al 1997;Aguirre et al 2002;Vajaranant et al 2002).…”

Section: Canine Modelssupporting

confidence: 70%

Gene Augmentation for X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR

Beltran

Cideciyan

Lewin

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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Section: Canine Modelssupporting

confidence: 70%

Gene Augmentation for X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR

Beltran

Cideciyan

Lewin

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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“…In 1985, autopsy eyes were first examined from a 79-year-old female carrier who had no visual symptoms and had normal visual acuity. 32 In this study of young individuals, the rods and cones in the posterior pole were within the normal limit, and scattered circular or oval patches of photoreceptor cell degeneration were observed in a midperipheral annulus. However, a recent study of an XLRP carrier with an RPGR mutation showed patches with abnormal or no photoreceptors and diminished numbers of cone cells in parafoveal and perifoveal regions, although she had a normal visual acuity.…”

mentioning

confidence: 51%

“…Our novel findings with AO-SLO were more comparable to the results from histological analyses of two recent histological studies than those of an earlier one. [32][33][34] Despite normal visual acuity and mildly subnormal ERG findings, every carrier had several subnormal areas, where distribution of cones were less compact, and abnormal cone cells, which appeared to form mosaic patterns from their size and shape. What is intriguing is the fact that there were no specific SD-OCT findings on all carriers, highlighting that it may not be possible to directly deduce the degree of cone cell structure from SD-OCT imaging alone.…”

mentioning

confidence: 99%

Cellular imaging demonstrates genetic mosaicism in heterozygous carriers of an X-linked ciliopathy gene

Hong

et al. 2013

Eur J Hum Genet

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X-linked retinitis pigmentosa (XLRP) is the least common genetic type of retinitis pigmentosa; however, it has extremely devastating consequences to patients' activities of daily living. RPGR and RP2 genes expressed in the photoreceptor sensory cilia are predominantly implicated in XLRP; however, the interpretation of genetic mutations and their correlation with clinical phenotypes remain unknown, and the role of these genes in photoreceptor cilia function is not completely elucidated. Therefore, we evaluated structural characteristics in five female obligate carriers of XLRP by using state-of-the-art non-invasive imaging methods, including adaptive optics (AO) scanning laser ophthalmoscopy (SLO). In all five carriers examined, qualitative and quantitative analyses by AO SLO imaging revealed a mosaic pattern of cone disruption, even in the absence of visual symptoms, normal visual acuity and normal macular thickness, on optical coherence tomography and mildly subnormal full-field cone electroretinographic findings. As the technique is sensitive to the level of a single cone, the ability to visualize the cone cells in vivo should be especially useful in other retinal diseases. In addition, further investigation of XLRP carriers may yield insight into how cone structures change over time and ultimately enable understanding of the role of RPGR and RP2 in cone cell survival. European Journal of Human Genetics (2013Genetics ( ) 21, 1240Genetics ( -1248 doi:10.1038/ejhg.2013; published online 27 February 2013Keywords: X-linked retinitis pigmentosa carrier; photoreceptor layer; adaptive optics scanning laser ophthalmoscopy INTRODUCTIONIdentification of X-linked retinitis pigmentosa (XLRP) carriers is challenging and has serious implications for genetic counseling. Female XLRP carriers usually have normal, or close to normal, visual acuity, but often show some degree of fundus changes, including sectorial or peripheral pigmentary deposits and a tapetal-like reflex (TLR), 1 as well as abnormal fundus. Many previous studies have detailed the prevalence of abnormal fundus photography, 1,2 vitreous fluorophotometry, 3 infrared (IR) reflectance images, 1,2 electroretinographic (ERG), 4,5 psychophysical 6 and flicker-fusion 7 findings in such carriers. More recently, several studies have investigated XLRP carriers with advanced devices, including FAF, 8 multifocal ERG 9 and OCT 10,11 to reveal clinical phenotypes of XLRP. Most XLRP carriers can be identified on the basis of fundus findings and ERG changes; however, 10-30% of carriers show no abnormal ERG or fundus finding. 1,4,5,9 Although XLRP is the least common genetic type of RP, accounting for 6-17% of familial retinitis pigmentosa cases, it is extremely devastating. 1,12,13 In the first or second decade of life, affected individuals experience a decrease in peripheral and night vision, and the disease often leads to partial or complete blindness in the fourth or fifth decade of life. 14 In contrast to the severe retinal degeneration in affected men, female carriers of t...

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“…In advanced RP with different forms of inheritance, loss of pure melanin granules and a marked increase of melanolysosomes within the RPE cells has been documented in areas with preserved retinal function corresponding to cones with residual outer segments, and intact cone synaptic pedicles. 2,[50][51][52] In contrast, RPE cells in the perifovea or near the optic disc underlying cone cell bodies without outer segments, and synaptic pedicles lost their melanin and contained no melanolysosomes. 50,53 Also, in areas with shortened and disorganized cone and rod outer segments, pyramidshaped RPE protuberances filled with melanin granules were found to surround cone but not rod outer segments.…”

Section: Discussionmentioning

confidence: 99%

Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa

Kellner

Weber

et al. 2008

Eye

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Aims To compare melanin-related nearinfrared fundus autofluorescence (FAF; NIA, excitation 787 nm, emission 4800 nm) with lipofuscin-related FAF (excitation 488 nm, emission 4500 nm) in retinitis pigmentosa (RP). Methods Thirty-three consecutive RP patients with different modes of inheritance were diagnosed clinically, with full-field ERG, and if possible with molecular genetic methods. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2). Results Rings of increased FAF were present within an area of preserved retinal pigment epithelium (RPE) at the posterior pole (31/33). Rings of increased NIA were located in the same region as rings of increased FAF. In contrast to FAF, NIA showed a precipitous decline of NIA peripheral to the ring. In larger areas of preserved NIA (11/31), pericentral and foveal NIA were of similar intensity with an area of lower NIA in between. In smaller areas of preserved NIA (20/31), NIA was homogeneous from the perifovea to the fovea. In one patient without a ring of increased FAF, NIA distribution was normal. In the remaining patient with severely advanced RP, no residual RPE as well as no FAF and NIA were detectable. Conclusion Characteristic features for FAF and NIA alterations in a heterogeneous group of RP patients indicate a common pathway of RPE degeneration. Patterns of NIA and FAF indicate different pathophysiologic processes involving melanin and lipofuscin. Combined NIA and FAF imaging will provide further insight into the pathogenesis of RP and noninvasive monitoring of future therapeutic interventions.

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Retinal Histopathology of a Carrier of X-chromosome-linked Retinitis Pigmentosa

Cited by 33 publications

References 19 publications

Gene Augmentation for X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR

Gene Augmentation for X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR

Cellular imaging demonstrates genetic mosaicism in heterozygous carriers of an X-linked ciliopathy gene

Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa

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