Transforming growth factor β isoforms in human optic nerve heads

• Published in: British journal of ophthalmology Vol. 83; no. 2; pp. 209 - 218
• Main Authors: Pena, Janethe D O, Taylor, Andrew W, Ricard, Cynthia S, Vidal, Ivonne, Hernandez, M Rosario
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01.02.1999; BMJ
• Subjects: Aged; Aged, 80 and over; astrocytes; Biological and medical sciences; Biomarkers; Female; Fetus; Gene Expression; glaucoma; Glaucoma and intraocular pressure; Glaucoma, Open-Angle - metabolism; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Ophthalmology; Optic Disk - metabolism; optic nerve head; Original; Transforming Growth Factor beta - biosynthesis; transforming growth factor β; Human; Immunohistochemistry; Eye disease; Head; Optic nerve; Transforming growth factor β; Glaucoma (eye); Adult; Exploration; Fetus; Isoforming; Comparative study
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjo.83.2.209

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.