RESUMEN
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 â¼17% 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.
Asunto(s)
Mutación , Canales de Potasio de Rectificación Interna/genética , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Anciano , Anciano de 80 o más Años , Animales , Membrana Celular/genética , Membrana Celular/metabolismo , Membrana Celular/patología , Coroides/metabolismo , Coroides/patología , Clonación Molecular/métodos , Electrofisiología/métodos , Femenino , Humanos , Células de Riñón Canino Madin Darby , Potenciales de la Membrana/genética , Oocitos/metabolismo , Potasio/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , ARN Complementario/genética , Ratas , Retina/metabolismo , Retina/patología , Degeneración Retiniana/metabolismo , Rubidio/metabolismo , Xenopus laevisRESUMEN
OBJECTIVE: To assess the safety and efficacy of combined cataract extraction, posterior chamber intraocular lens placement, pars plana vitrectomy, fluocinolone acetonide intravitreal implant (Retisert), and Ahmed valves with pars plana tube (CPR-PT) in eyes with chronic, posterior, noninfectious uveitis. METHODS: Retrospective study of patients who underwent CPR-PT. Outcome measures included visual acuity, intraocular pressure, inflammation, and complications. RESULTS: Eight eyes were included, with a mean follow-up of 18 months. Mean visual acuity improved from 1.89 to 0.14 logMAR (Snellen, counting fingers at 2 ft [0.6 m]) to 20/30; P=.01). Mean intraocular pressure remained stable at 16 to 17 mm Hg (P=.35). The number of glaucoma medications per eye decreased from 2.9 to 0.25 (P=.01). Systemic prednisone therapy was discontinued in all patients by 9 months postoperatively. Inflammation was well controlled in all eyes. CONCLUSION: The CPR-PT procedure allows rapid visual rehabilitation without major short-term complications.