RESUMEN
Advances in genetic tools and sequencing technology in the past few years have vastly expanded our understanding of the genetics of neurodevelopmental disorders. Recent high-throughput sequencing analyses of structural brain malformations, cognitive and neuropsychiatric disorders, and localized cortical dysplasias have uncovered a diverse genetic landscape beyond classic Mendelian patterns of inheritance. The underlying genetic causes of neurodevelopmental disorders implicate numerous cell biological pathways critical for normal brain development.
Asunto(s)
Corteza Cerebral/patología , Trastornos Generalizados del Desarrollo Infantil/genética , Malformaciones del Desarrollo Cortical/genética , Neuronas/patología , Alelos , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/metabolismo , Niño , Trastornos Generalizados del Desarrollo Infantil/patología , Citoesqueleto/genética , Citoesqueleto/patología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Dedos/anomalías , Dedos/patología , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Malformaciones del Desarrollo Cortical/patología , Microcefalia/genética , Microcefalia/patología , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Miopía/genética , Miopía/patología , Neuronas/metabolismo , Obesidad/genética , Obesidad/patología , Degeneración RetinianaRESUMEN
PURPOSE: To report the outcomes of intracameral tissue plasminogen activator (tPA) use during uveitic cataract surgery. DESIGN: Retrospective case series from a single United States tertiary center of 36 eyes from 31 consecutive patients with established uveitis who received intraoperative intracameral tPA during cataract surgery between 2016 and 2020. RESULTS: Mean visual acuity (VA) improved from logMAR 1.0 ± 0.7 preoperatively to logMAR 0.7 ± 0.8 by POM12. VA improved from baseline postoperatively (POM1 p = 0.0002, POM6 p = 0.006 and POM12 p = 0.007). Minimal to no anterior chamber inflammation was achieved in 47.2% of the eyes by POW1 and 80.0% of the eyes by POM1. Mean clock-hours of posterior synechiae improved from 8.2 ± 3.8 preoperatively to 0.1 ± 0.6 by POM12. Six eyes developed hyphema and/or vitreous hemorrhage, four of which resolved spontaneously. CONCLUSIONS: Adjunctive intracameral tPA during uveitic cataract surgery improves VA and intraocular inflammation, but risks postoperative hemorrhage. Intraoperative tPA as adjunctive anti-inflammatory therapy warrants randomized prospective studies.
RESUMEN
Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development.