Transforming growth factor beta isoforms in human optic nerve heads.
OBJECTIVE
To determine if the isoforms of transforming growth factor beta (TGF-beta) are present in fetal, normal adult, and glaucomatous optic nerve heads.


METHODS
To localise cells synthesising TGF-beta, optic nerve heads were stained using antibodies to TGF-beta 1, TGF-beta 2, and TGF-beta 3. 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-beta 1 and TGF-beta 2 by bioassay. 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-beta 1 was localised to blood vessels. No TGF-beta 3 immunoreactivity was observed. There was little or no expression of TGF-beta in normal optic nerve heads. Optic nerve heads from glaucomatous eyes released 70-100-fold more TGF-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 levels in the fetal and glaucomatous optic nerve heads, perhaps by a mechanism of post-transcriptional regulation. TGF-beta may be important during development of the optic nerve head and, in glaucoma, TGF-beta 2 may be a mediator of astrocyte reactivation and extracellular matrix remodelling in the lamina cribrosa.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis 63110, USA.
J D
JD
Pena
A W
AW
Taylor
C S
CS
Ricard
I
I
Vidal
M R
MR
Hernandez
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D005333:Fetus; D015870:Gene Expression; D005902:Glaucoma, Open-Angle / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D015415:Biomarkers; D016212:Transforming Growth Factor beta