Aqueous Humor in Glaucomatous Eyes Contains an Increased Level of TGF-β2

Abstract

By using the highly sensitive and specific technique of enzyme-linked immunosorbent assay, we investigated the presence and amount of transforming growth factor-β2 (TGF-β2) in samples of aqueous humor obtained from 15 patients who had a clinically established diagnosis of advanced primary open-angle glaucoma (POAG), as well as from ten age-matched normal human subjects undergoing cataract surgery. The total amount of TGF-β2 in the samples of normal aqueous humor ranged from 0·41 to 2.24 ng ml -1 (mean ± S.D.: 1·48 ± 0·68 ng ml -1) of which 4·88 to 37·05% (11·99 ± 9·95%) was intrinsically active. Compared with normal subjects, the aqueous humor from POAG patients had a statistically significantly greater amount of total TGF-β2 (2·70 ± 0·76 ng ml -1 P < 0·01), AS WELL AS A HIGHER LEVEL OF INTRINSICALLY ACTIVE TGF-β2 (0·45 ± 0·28 NG ML -1, P < 0·05) which corresponded to 1·09 to 60·84% (18·33 ± 15·50%) of the total amount. No linear correlation was found between the age of the subjects and the protein concentration of the aqueous humor from either normal or glaucomatous eyes, nor between the age of the patient and the total amount of TGP-β2. The negligible amount of TGF-β2 present in serum argues against its influx into the aqueous humor after breakdown of the blood-aqueous barrier that is known to occur in glaucomatous eyes; rather, our present findings support the concept of the intraocular derivation of this cytokine. Because of the growth-inhibitory actions of TGF-β on trabecular cells in vitro and its role in promoting the synthesis and deposition of extracellular matrix (ECM) components, we hypothesize that the increased level of TGF-β2 in the aqueous humor of POAG patients causes a decrease in the cellularity of the trabecular meshwork and promotes the buildup of excessive amounts of ECM materials that are characteristic of this disease and contribute to the increased resistance to aqueous outflow.