Distribution and expression of transforming growth factor-beta and platelet-derived growth factor in the normal and glaucomatous monkey optic nerve heads.

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) in the optic nerve head in an experimentally induced glaucoma model. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after photocoagulation. The optic nerve head was examined for expression of TGF-beta1, -beta2 and -beta3 and PDGF-A and -B in frozen sections and by the biotin ExtraAvidin-alkali phosphatase method. RESULTS: Normal monkey eyes showed TGF-beta1, -beta2 and -beta3, and PDGF-A and -B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF-beta1 and -beta2 in the glial cells around the lamina cribrosa. The staining intensities for TGF-beta3, PDGF-A and -B were the same as in normal eyes. CONCLUSIONS: Eyes with experimental glaucoma showed higher expression of TGF-beta1 and -beta2 around the lamina cribrosa. These findings may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.

[Changes in transforming growth factor-beta and platelet-derived growth factor in the optic nerve head in monkey experimental glaucoma].

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet derived growth factor (PDGF) in the optic nerve heads in experimentally induced glaucoma. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after treatment. The optic nerve head was examined for expression of TGF beta 1, beta 2, and beta 3, and PDGF A and B in frozen sections and by the biotin-ExtrAvidin-Alkali Phosphatase method. FINDINGS: Normal monkey eyes showed TGF beta 1, beta 2, and beta 3, and PDGF A, and B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF beta 1 and beta 2 in the glial cells around the lamina cribrosa. The staining intensities for TGF beta 3, PDGF A, and PDGF B were the same as in normal eyes. CONCLUSION: Eyes with experimental glaucoma showed higher expressions of TGF beta 1 and beta 2 around the lamina cribrosa. This finding may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.

Effects of mitomycin C on the expression of proliferating cell nuclear antigen after filtering surgery in rabbits.

BACKGROUND: The aim of the study was to evaluate the effects of mitomycin C on the cell replication activity in wound healing following experimental filtration surgery. METHODS: Trabeculectomy with or without application of mitomycin C was performed on albino rabbit eyes. At 1, 4, 7, 14, and 28 days after surgery, the expression of proliferating cell nuclear antigen, a marker of cell proliferation, in the filtering site was examined immunohistochemically using a streptavidin-biotin complex method. RESULTS: In control eyes that underwent trabeculectomy but did not receive mitomycin C, the number of immunoreactive cells increased 4-7 days after operation and decreased markedly at around 14 days. The filtering site was obstructed histologically at 4-7 days after operation. In the mitomycin C-treated eyes, immunoreactive cells appeared 4 days after surgery but disappeared by 7 days at the surgical site. The number of immunoreactive cells in the treated eyes was much lower than that in control eyes. CONCLUSION: The cell replication activity was markedly inhibited by administration of mitomycin C. The filtering site remained open for 28 days after surgery, whereas it was completely obstructed within 7 days in control eyes. Immunocytochemistry for proliferating cell nuclear antigen, as used in this study, is a simple and reliable method for detection of cell replication activity.

[Extracellular matrix of the optic nerve lamina cribrosa in monkey eyes with experimentally induced glaucoma].

The changes of immunoreactivity and immunolocalization of the extracellular matrices (ECM), collagen type I through VI, laminin, fibronectin and alpha-elastin, of optic nerve lamina cribrosa in argon laser induced glaucoma in monkey eyes were examined using a immunohistochemical method, biotin-streptavidin system. The results were consistent with the previous findings that in the experimental glaucoma eyes, diffuse immunoreactivity of collagen type I, III, V, VI, fibronectin were detected in the thickened and irregular laminar beams, while linear staining for collagen type IV and laminin were seen around the laminar beams and vascular walls were densely, thickly and irregularly, and furthermore immunoreactivity for alpha-elastin was reduced markedly in the glial columns and moderately in the lamina cribrosa. In the lamina cribrosa with optic disc cupping in laser-induced monkey glaucoma, the immunoreactivity for alpha-elastin was changed most greatly, and no qualitative differences were detected in comparison with normal fellow eyes for the other ECM components.

[Optic disc measurements with computerized image analysis in experimental chronic glaucoma].

We quantitatively analyzed morphological changes of the optic disc of ten Japanese monkey eyes exposed to sustained intraocular pressure (IOP) elevation by repeated argon laser application to the trabecular meshwork. Using a computerized image analyzer (Topcon IMAGEnet), we measure the cup-disc ratio (CDR), disc area (DA), cup volume/disc area (CV/DA), and rim area/disc area (RA/DA). The duration of IOP elevation was 48.4 +/- 0.8 (mean +/- SD) weeks, and the mean IOP during the experiment was 26.3 +/- 2.6 mmHg [the mean IOP during the experiment/pre-treatment IOP was 2.05 +/- 0.55 (IOP ratio)]. In advanced glaucomatous eyes (the duration of IOP elevation of approximately one year), comparing pretreatment, the CV/DA increased 4.96 times, the vertical CDR increased 1.78 times, the horizontal CDR increased 1.69 times, the DA increased 1.42 times, and the RA/DA decreased 0.54 times. A significant positive correlation was found between the IOP ratio and, both the vertical CDR (gamma = 0.65) and the CV/DA (gamma = 0.68). These results suggested that the development of glaucomatous optic disc cupping correlated with the degree of IOP elevation in monkey eyes. Using this computer image analyser, the longitudinal quantitative follow-up of disc changes of experimental glaucoma may be useful for understanding the mode of human glaucomatous optic nerve damage.