Delineation of a Specific Case of Vitreoretinal Degeneration

2015 ◽  
pp. 12-13
Keyword(s):  
Vitreoretinal Degeneration

Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14

1999 ◽  
Vol 237 (5) ◽  
pp. 387-393 ◽  
Author(s):  
Jean-Christophe Zech ◽  
Laurette Morlé ◽  
Pascale Vincent ◽  
Nicole Alloisio ◽  
Muriel Bozon ◽  
...  
Keyword(s):  
Genetic Linkage ◽  
Vitreoretinal Degeneration

scholarly journals Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy

2013 ◽  
Vol 304 (5) ◽  
pp. C440-C449 ◽  
Author(s):  
Wei Zhang ◽  
Xiaoming Zhang ◽  
Hui Wang ◽  
Anil K. Sharma ◽  
Albert O. Edwards ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Expression System ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Xenopus Laevis Oocyte ◽  
Cation Selectivity ◽  
Negative Effect ◽  
Dominant Disease ◽  
Vitreoretinal Degeneration ◽  
Inwardly Rectifying

KCNJ13 encodes Kir7.1, an inwardly rectifying K+ channel that is expressed in multiple ion-transporting epithelia. A mutation in KCNJ13 resulting in an arginine-to-tryptophan change at residue 162 (R162W) of Kir7.1 was associated with snowflake vitreoretinal degeneration, an inherited autosomal-dominant disease characterized by vitreous degeneration and mild retinal degeneration. We used the Xenopus laevis oocyte expression system to assess the functional properties of the R162W (mutant) Kir7.1 channel and determine how wild-type (WT) Kir7.1 is affected by the presence of the mutant subunit. Recordings obtained via the two-electrode voltage-clamp technique revealed that injection of oocytes with mutant Kir7.1 cRNA resulted in currents and cation selectivity that were indistinguishable from those in water-injected oocytes, suggesting that the mutant protein does not form functional channels in the plasma membrane. Coinjection of oocytes with equal amounts of mutant and WT Kir7.1 cRNAs resulted in inward K+ and Rb+ currents with amplitudes that were ∼17% of those in oocytes injected with WT Kir7.1 cRNA alone, demonstrating a dominant-negative effect of the mutant subunit. Similar to oocytes injected with WT Kir7.1 cRNA alone, coinjected oocytes exhibited inwardly rectifying Rb+ currents that were more than seven times larger than K+ currents, indicating that mutant subunits did not alter Kir7.1 channel selectivity. Immunostaining of Xenopus oocytes or Madin-Darby canine kidney cells expressing mutant or WT Kir7.1 demonstrated distribution of both proteins primarily in the plasma membrane. Our data suggest that the R162W mutation suppresses Kir7.1 channel activity, possibly by negatively impacting gating by membrane phosphadidylinositol 4,5-bisphosphate.

scholarly journals VCANCanonical Splice Site Mutation is Associated With Vitreoretinal Degeneration and Disrupts an MMP Proteolytic Site

2019 ◽  
Vol 60 (1) ◽  
pp. 282 ◽  
Author(s):  
Peter H. Tang ◽  
Gabriel Velez ◽  
Stephen H. Tsang ◽  
Alexander G. Bassuk ◽  
Vinit B. Mahajan
Keyword(s):  
Splice Site ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Proteolytic Site ◽  
Vitreoretinal Degeneration

Clinical Variability in Vitreoretinal Degeneration

1983 ◽  
Vol 33 (3) ◽  
pp. 153-159 ◽  
Author(s):  
Victor Godel ◽  
Lucian Regenbogen ◽  
Vera Feiler-Ofry ◽  
Moshe Lazar
Keyword(s):  
Clinical Variability ◽  
Vitreoretinal Degeneration

Vitrectomy and Wagner'S Vitreoretinal Degeneration

1978 ◽  
Vol 86 (4) ◽  
pp. 485-488 ◽  
Author(s):  
Gary C. Brown ◽  
William S. Tasman
Keyword(s):  
Vitreoretinal Degeneration

Genetic Linkage of Snowflake Vitreoretinal Degeneration to Chromosome 2q36

2004 ◽  
Vol 45 (12) ◽  
pp. 4498 ◽  
Author(s):  
Xiaodong Jiao ◽  
Robert Ritter ◽  
J. Fielding Hejtmancik ◽  
Albert O. Edwards
Keyword(s):  
Genetic Linkage ◽  
Vitreoretinal Degeneration

scholarly journals Retinal Development and Pathophysiology in Kcnj13 Knockout Mice

2022 ◽  
Vol 9 ◽  
Author(s):  
Xiaodong Jiao ◽  
Zhiwei Ma ◽  
Jingqi Lei ◽  
Pinghu Liu ◽  
Xiaoyu Cai ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Knockout Mice ◽  
Ciliary Body ◽  
Outer Nuclear Layer ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Conditional Knockout ◽  
Intron 1 ◽  
Vitreoretinal Degeneration ◽  
Inwardly Rectifying

Purpose: We constructed and characterized knockout and conditional knockout mice for KCNJ13, encoding the inwardly rectifying K+ channel of the Kir superfamily Kir7.1, mutations in which cause both Snowflake Vitreoretinal Degeneration (SVD) and Retinitis pigmentosa (RP) to further elucidate the pathology of this disease and to develop a potential model system for gene therapy trials.Methods: A Kcnj13 knockout mouse line was constructed by inserting a gene trap cassette expressing beta-galactosidase flanked by FRT sites in intron 1 with LoxP sites flanking exon two and converted to a conditional knockout by FLP recombination followed by crossing with C57BL/6J mice having Cre driven by the VMD2 promoter. Lentiviral replacement of Kcnj13 was driven by the EF1a or VMD2 promoters.Results: Blue-Gal expression is evident in E12.5 brain ventricular choroid plexus, lens, neural retina layer, and anterior RPE. In the adult eye expression is seen in the ciliary body, RPE and choroid. Adult conditional Kcnj13 ko mice show loss of photoreceptors in the outer nuclear layer, inner nuclear layer thinning with loss of bipolar cells, and thinning and disruption of the outer plexiform layer, correlating with Cre expression in the overlying RPE which, although preserved, shows morphological disruption. Fundoscopy and OCT show signs of retinal degeneration consistent with the histology, and photopic and scotopic ERGs are decreased in amplitude or extinguished. Lentiviral based replacement of Kcnj13 resulted in increased ERG c- but not a- or b- wave amplitudes.Conclusion: Ocular KCNJ13 expression starts in the choroid, lens, ciliary body, and anterior retina, while later expression centers on the RPE with no/lower expression in the neuroretina. Although KCNJ13 expression is not required for survival of the RPE, it is necessary for RPE maintenance of the photoreceptors, and loss of the photoreceptor, outer plexiform, and outer nuclear layers occur in adult KCNJ13 cKO mice, concomitant with decreased amplitude and eventual extinguishing of the ERG and signs of retinitis pigmentosa on fundoscopy and OCT. Kcnj13 replacement resulting in recovery of the ERG c- but not a- and b-waves is consistent with the degree of photoreceptor degeneration seen on histology.

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