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Neuronal and glial cell alterations involved in the retinal degeneration of the familial dysautonomia optic neuropathy.
Schultz, Anastasia; Albertos-Arranz, Henar; Sáez, Xavier Sánchez; Morgan, Jamie; Darland, Diane C; Gonzalez-Duarte, Alejandra; Kaufmann, Horacio; Mendoza-Santiesteban, Carlos E; Cuenca, Nicolás; Lefcort, Frances.
Afiliación
  • Schultz A; Department of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
  • Albertos-Arranz H; Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
  • Sáez XS; Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
  • Morgan J; Department of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
  • Darland DC; Department of Biology, University of North Dakota, Grand Forks, North Dakota, USA.
  • Gonzalez-Duarte A; Department of Neurology, NYU Langone Health, New York, New York, USA.
  • Kaufmann H; Department of Neurology, NYU Langone Health, New York, New York, USA.
  • Mendoza-Santiesteban CE; Department of Neurology, NYU Langone Health, New York, New York, USA.
  • Cuenca N; Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.
  • Lefcort F; Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Glia ; 2024 Sep 03.
Article en En | MEDLINE | ID: mdl-39228100
ABSTRACT
Familial dysautonomia (FD) is a rare genetic neurodevelopmental and neurodegenerative disorder. In addition to the autonomic and peripheral sensory neuropathies that challenge patient survival, one of the most debilitating symptoms affecting patients' quality of life is progressive blindness resulting from the steady loss of retinal ganglion cells (RGCs). Within the FD community, there is a concerted effort to develop treatments to prevent the loss of RGCs. However, the mechanisms underlying the death of RGCs are not well understood. To study the mechanisms underlying RGC death, Pax6-cre;Elp1loxp/loxp male and female mice and postmortem retinal tissue from an FD patient were used to explore the neuronal and non-neuronal cellular pathology associated with the FD optic neuropathy. Neurons, astrocytes, microglia, Müller glia, and endothelial cells were investigated using a combination of histological analyses. We identified a novel disruption of cellular homeostasis and gliosis in the FD retina. Beginning shortly after birth and progressing with age, the FD retina is marked by astrogliosis and perturbations in microglia, which coincide with vascular remodeling. These changes begin before the onset of RGC death, suggesting alterations in the retinal neurovascular unit may contribute to and exacerbate RGC death. We reveal for the first time that the FD retina pathology includes reactive gliosis, increased microglial recruitment to the ganglion cell layer (GCL), disruptions in the deep and superficial vascular plexuses, and alterations in signaling pathways. These studies implicate the neurovascular unit as a disease-modifying target for therapeutic interventions in FD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos