Collagen metabolism in human aqueous humor from primary open-angle glaucoma. Decreased degradation and increased biosynthesis play a role in its pathogenesis
G. Gonzalez-Avila, M. Ginebra, T. Hayakawa, F. Vadillo-Ortega, L. Teran and M. Selman
Department of Molecular Biology, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
OBJECTIVE: To explore the influence of aqueous humor from patients with
glaucoma on collagen turnover. METHODS: The aqueous humor of patients with
primary open-angle glaucoma (POAG), chronic angle-closure glaucoma,
congenital glaucoma, neovascular glaucoma, and senile cataract (control
group) was analyzed for its capacity to induce fibroblast proliferation,
collagen synthesis, collagenolytic activity, and production of tissue
inhibitor of metalloproteinase-1. All data were analyzed using the
Mann-Whitney U test. RESULTS: Aqueous humor derived from patients with POAG
induced a significant decrease of functional collagenase activity (mean +/-
SE, 9.12 +/- 1.33 microgram of degraded collagen per milligram of incubated
protein vs 20.94 +/- 4.14 micrograms from the control group, P < .05).
The enzymatic activity in the other types of glaucoma was similar to that
of controls. The POAG samples had a significantly higher concentration of
tissue inhibitor of metalloproteinase-1 (mean +/- SE, 3.11 +/- 0.58 vs 0.91
+/- 0.13 micrograms/mL from controls; P < .05). The amount of
immunoreactive tissue inhibitor of metalloproteinase-1 found in the other
three groups was not significantly different from the control. Aqueous
humor stimulated fibroblast proliferation in all cases, but significant
differences were not observed between the POAG samples (mean +/- SE, 20,285
+/- 4642 cpm/mg of incubated protein) and the control group samples (26,550
+/- 3688 cpm/mg of incubated protein). Primary open-angle glaucoma fluids
increased collagen synthesis significantly compared with the control group
(mean +/- SD, 3352 +/- 630 vs 985 +/- 285, P < .05), and the other
groups. CONCLUSIONS: An increase of collagen synthesis and a decrease of
collagen degradation may contribute to an excessive deposit of collagen
with loss of the trabecular cells during the development of POAG, and
aqueous humor must be considered as a microenvironment that affects the
metabolism or function of the trabecular meshwork or both.
