Synthesis of elastic microfibrillar components fibrillin-1 and fibrillin-2by human optic nerve head astrocytes in situ and in vitro

The purpose of this study was to identify elastic microfibrillar components fibrillin-1 and fibrillin-2 in optic nerve heads of adult normal and glauc omatous subjects. in cultured optic nerve head astrocytes (type 1B astrocyt es), as well as fibrillin-1 in fetal optic nerve heads. To characterize syn thesis and gene expression of microfibrillar proteins in human optic nerve heads and cultured type 1B astrocytes, light microscopy immunohistochemistr y, in situ hybridization, and RT-PCR or Northern blots were performed. Our results demonstrated that fibrillin-1 was associated with blood vessels, as trocytes in the glial columns and cribriform plates, and with astrocyte pro cesses in the nerve bundles in all samples. In glaucomatous optic nerves th ere was enhanced fibrillin-1 immunoreactivity, especially surrounding blood Vessels. Fibrillin-2 was localized primarily to brood Vessels in all sampl es, without qualitative differences between normal and glaucomatous samples , In fetal optic nerve heads fibrillin-1. mRNA was localized to glial cells and to the blood vessel walls, In adult optic nerve heads, there was littl e fibrillin-1 mRNA as detectable by in situ hybridization and RT-PCR. There was no detectable upregulation of fibrillin-1 mRNA in glaucoma. In culture d type 1B astrocytes, fibrillin-1 staining was mostly pericellular.. There was little fibrillin-2 immunoreactivity. In conclusion astrocytes from the optic nerve head deposit elastic microfibrillar components in situ and in v itro, with a predominance of fibrillin-1. Upregulation of fibrillin-1 mRNA was not observed in glaucoma, suggesting that increased transcription may o ccur early in the disease process. Cultures of type 1B astrocytes from the optic nerve head provides a useful model to study mechanisms regulating the interactions of elastin and the microfibrils in optic nerve head astrocyte s. (C) 2000 Academic Press.