Collagen metabolism in human aqueous humor from primary open-angle glaucoma. Decreased degradation and increased biosynthesis play a role in its pathogenesis.
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.
González-Avila
G
G
Department of Molecular Biology, Instituto Nacional de Enfermedades Respiratorias, México City, México.
Ginebra
M
M
Hayakawa
T
T
Vadillo-Ortega
F
F
Terán
L
L
Selman
M
M
D000328:Adult; D000368:Aged; D001082:Aqueous Humor / Q000378:metabolism*; D002455:Cell Division; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D005901:Glaucoma / Q000151:congenital / Q000378:metabolism; D015812:Glaucoma, Angle-Closure / Q000378:metabolism / Q000601:surgery; D015355:Glaucoma, Neovascular / Q000378:metabolism; D005902:Glaucoma, Open-Angle / Q000209:etiology* / Q000378:metabolism* / Q000601:surgery; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D011480:Protease Inhibitors / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D017364:Collagenases