Optic Nerve Head Astrocytes Display Axon-Dependent and -Independent Reactivity in Response to Acutely Elevated Intraocular Pressure.
Invest Ophthalmol Vis Sci
; 60(1): 312-321, 2019 01 02.
Article
em En
| MEDLINE
| ID: mdl-30665231
ABSTRACT
Purpose:
Optic nerve head (ONH) astrocytes provide support for axons, but exhibit structural and functional changes (termed reactivity) in a number of glaucoma models. The purpose of this study was to determine if ONH astrocyte structural reactivity is axon-dependent.Methods:
Using rats, we combine retrobulbar optic nerve transection (ONT) with acute controlled elevation of intraocular pressure (CEI), to induce total optic nerve axon loss and ONH astrocyte reactivity, respectively. Animals were euthanized immediately or 1 day post CEI, in the presence or absence of ONT. ONH sections were labeled with fluorescent-tagged phalloidin and antibodies against ß3 tubulin, phosphorylated cortactin, phosphorylated paxillin, or complement C3. ONH label intensities were quantified after confocal microscopy. Retrobulbar nerves were assessed for axon injury by light microscopy.Results:
While ONT alone had no effect on ONH astrocyte structural orientation, astrocytes demonstrated significant reorganization of cellular extensions within hours after CEI, even when combined with ONT. However, ONH astrocytes displayed differential intensities of actin (phosphorylated cortactin) and focal adhesion (phosphorylated paxillin) mediators in response to CEI alone, ONT alone, or the combination of CEI and ONT. Lastly, label intensities of complement C3 within the ONH were unchanged in eyes subjected to CEI alone, ONT alone, or the combination of CEI and ONT, relative to controls.Conclusions:
Early ONH astrocyte structural reactivity to elevated IOP is multifaceted, displaying both axon dependent and independent responses. These findings have important implications for pursuing astrocytes as diagnostic and therapeutic targets in neurodegenerative disorders with fluctuating levels of axon injury.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Disco Óptico
/
Axônios
/
Hipertensão Ocular
/
Astrócitos
/
Modelos Animais de Doenças
/
Pressão Intraocular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos