Transforming growth factor beta isoforms in human optic nerve heads

Aims-To determine if the isoforms of transforming growth factor beta (TGF-b eta) are present in fetal, normal adult, and glaucomatous optic nerve heads . Methods-To localise cells synthesising TGF-beta, optic nerve heads were sta ined using antibodies to TGF-beta 1, TGF-beta 2, and TGF-beta 3. To demonst rate synthesis, human optic nerve heads from fetal, glaucomatous, and norma l age matched subjects were explanted, cultured overnight, and the culture supernatant was assayed for the presence of TGF-beta 1 and TGF-beta 2 by bi oassay. In addition, semiquantitative RT-PCR was performed to determine the gene expression pattern of TGF-beta 2. Results-Immunohistochemistry of glaucomatous samples revealed the presence of intense staining for TGF-beta 2 primarily in astrocytes, whereas TGF-bet a 1 was localised to blood vessels. No TGF-beta 3 immunoreactivity was obse rved. There was little or no expression of TGF-beta in normal optic nerve h eads. Optic nerve heads from glaucomatous eyes released 70-100-fold more TG F-beta 2 than normal age matched optic nerve heads. Fetal optic nerve heads released 90-100-fold more TGF-beta 2 than normal adult optic nerve heads. TGF-beta 1 was undetectable by bioassay in all samples tested. There was no apparent increase in TGF-beta 2 gene expression in glaucomatous and fetal eyes, suggesting post-transcriptional regulatory mechanisms. Conclusions-These results demonstrate that TGF-beta 2 is produced in high l evels in the fetal and glaucomatous optic nerve heads, perhaps by a mechani sm of post-transcriptional regulation. TGF-beta may be important during dev elopment of the optic nerve head and, in glaucoma, TGF-beta 2 may be a medi ator of astrocyte reactivation and extracellular matrix remodelling in the lamina cribrosa.