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Abstract #5570 Published in IGR 2-1
Differential expression of neural cell adhesion molecule isoforms in normal and glaucomatous human optic nerve heads
Ricard CS; Pena JD; Hernandez MRMolecular Brain Research 1999; 74:69-82
Type 1B astrocytes of the human optic nerve head (ONH) constitutively express neural cell adhesion molecule (NCAM) in vivo and in vitro. Increased synthesis of NCAM has been detected in reactive astrocytes in the glaucomatous ONH of human donor eyes. Several NCAM isoforms are generated through alternate RNA splicing in tissue- and disease-specific patterns. In this study, the authors analyzed expression of NCAM isoforms in ONH of normal donors at different ages and in glaucoma. Total RNA was extracted from ONH of fetal, normal adult and glaucomatous eyes, and cultured human ONH astrocytes, fetal brain astrocytes and an astrocytoma cell line, for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. To distinguish between NCAM 180 and 140 isoforms, exon-specific primer sets covering exons 13-19 were used. Isoform-specific riboprobes were used for in situ hybridization (ISH) in glaucomatous and in age-matched ONH. By RT-PCR, NCAM 140 was the predominant isoform in adult ONH as well as in all cultured cells. NCAM 180 mRNA was strongly expressed in glaucoma, whereas in normal adult tissues it was not detectable. ISH confirmed expression of NCAM in normal adult ONH and localized NCAM 140 mRNA to astrocytes. ISH demonstrated expression of NCAM 180 mRNA in reactive astrocytes in glaucomatous ONH. These results demonstrate that the NCAM 180 isoform is induced in glaucoma. NCAM 180 may play a role in astrocyte interaction with extracellular matrix (ECM), vessels, axons and other astrocytes and, through its expanded cytoplasmic domain, serve as a signalling molecule for reactive astrocytes during remodelling of the ONH in glaucoma.
Dr. C.S. Ricard, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8096, St Louis, MO 63110, USA
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.4 Molecular genetics (Part of: 3 Laboratory methods)
