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Br J Ophthalmol 83:209-218 doi:10.1136/bjo.83.2.209
  • Original Article
    • Laboratory science

Transforming growth factor β isoforms in human optic nerve heads

Abstract

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.

Footnotes

  • Present address: Department of Neuroscience Graduate Program, University of Pennsylvania, Philadelphia, PA, USA.