Transforming growth factor β isoforms in human optic nerve heads
- aDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, USA, bDepartment of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, USA, cSchepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, USA
- M Rosario Hernandez, DDS, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S Euclid Avenue, Box 8096, St Louis, MO 63110, USA.
- Accepted 30 July 1998
AIM To determine if the isoforms of transforming growth factor β (TGF-β) are present in fetal, normal adult, and glaucomatous optic nerve heads.
METHODS To localise cells synthesising TGF-β, optic nerve heads were stained using antibodies to TGF-β1, TGF-β2, and TGF-β3. To demonstrate synthesis, human optic nerve heads from fetal, glaucomatous, and normal age matched subjects were explanted, cultured overnight, and the culture supernatant was assayed for the presence of TGF-β1 and TGF-β2 by bioassay. In addition, semiquantitative RT-PCR was performed to determine the gene expression pattern of TGF-β2.
RESULTS Immunohistochemistry of glaucomatous samples revealed the presence of intense staining for TGF-β2 primarily in astrocytes, whereas TGF-β1 was localised to blood vessels. No TGF-β3 immunoreactivity was observed. There was little or no expression of TGF-β in normal optic nerve heads. Optic nerve heads from glaucomatous eyes released 70–100-fold more TGF-β2 than normal age matched optic nerve heads. Fetal optic nerve heads released 90–100-fold more TGF-β2 than normal adult optic nerve heads. TGF-β1 was undetectable by bioassay in all samples tested. There was no apparent increase in TGF-β2 gene expression in glaucomatous and fetal eyes, suggesting post-transcriptional regulatory mechanisms.
CONCLUSIONS These results demonstrate that TGF-β2 is produced in high levels in the fetal and glaucomatous optic nerve heads, perhaps by a mechanism of post-transcriptional regulation. TGF-β may be important during development of the optic nerve head and, in glaucoma, TGF-β2 may be a mediator of astrocyte reactivation and extracellular matrix remodelling in the lamina cribrosa.
↵Present address: Department of Neuroscience Graduate Program, University of Pennsylvania, Philadelphia, PA, USA.