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Abstract #15732 Published in IGR 2-3
Selective expression of neural cell adhesion molecule (NCAM)-180 in optic nerve head astrocytes exposed to elevated hydrostatic pressure in vitro
Ricard CS; Kobayashi S; Pena JDO; Salvador-Silva M; Agapova O; Hernandez MRMolecular Brain Research 2000; 81: 62-79
Glaucomatous optic neuropathy is usually associated with elevated intraocular pressure. Optic nerve head astrocytes may respond to intraocular pressure by stimulation of pressure-sensitive mechanoreceptors on the cell surface. Neural cell adhesion molecule (NCAM) a transmembrane protein, mediates cell adhesion and migration. The NCAM 180 isoform increases in astrocytes of glaucomatous optic nerve head. The authors characterized the relative expression of NCAM isoforms in human optic nerve head astrocytes grown under elevated hydrostatic pressure. Astrocytes cultured from normal human optic nerve heads were exposed to either atmospheric or continuous hydrostatic pressure of 60 mmHg, and analyzed at 6-48 hours. Changes in cell shape, immunoreactivity, and distribution of GFAP, actin and NCAM were observed in pressure-treated cultures. Newly synthesized sup(35) S-labelled NCAM protein immunoprecipitated from cell lysates was increased two-fold within 24 hours after exposure to elevated pressure compared to control. The increase in NCAM synthesis was primarily due to the NCAM 180 isoform. A significant increase in NCAM 180 mRNA levels was detected by RT-PCR and Northern blots in cultured optic nerve head astrocytes within six hours after exposure to elevated pressure. NCAM 180 mRNA and protein synthesis decreased after 24 hours and returned to control levels by 48 hours. These data indicate that NCAM 180 transcription and synthesis in astrocytes is stimulated by elevated hydrostatic pressure. Because NCAM 180 interacts with the cytoskeleton through an extended cytoplasmic tail, a selective and transient increase in NCAM 180 in optic nerve head astrocytes exposed to elevated pressure may be relevant to the migration and interactions of reactive astrocytes in glaucoma.
Dr. M.R. Hernandez, Department of Ophthalmology/Visual Science, Washington University School of Medicine, St. Louis, MO 63110, USA
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
4 Tissue culture of ocular cells
