Elevated levels of transforming growth factor beta and prostaglandin E2 in aqueous humor from patients undergoing filtration surgery for glaucoma.

Accumulating evidence suggests that substances present in aqueous humor may mediate the fibrosis that occurs in patients with glaucoma, particularly in those patients who undergo filtration surgery by insertion of aqueous humor drainage implants. Prostaglandins and polypeptide growth factors are proinflammatory substances that have been found in raised amounts in samples of aqueous humor obtained at the time of cataract removal or glaucoma surgery.1–3 Transforming growth factor β (TGFβ) is of particular interest since this pleiotropic growth factor, which has a ubiquitous tissue distribution, plays a key role in inflammation and fibrosis. In this study, we wished to determine whether the brisk, and often very severe, fibrotic reaction occurring after insertion of Molteno implants, which is accompanied by a sustained rise in intraocular pressure known as the hypertensive phase, is associated with enhanced production of prostaglandins and TGFβ. A total of 38 patients were enrolled in the study and, after informed consent was obtained, samples of aqueous humor were harvested and stored at –70 oC until tested. Estimations of the relative amounts of prostaglandin E2 (PGE2) were made by enzyme-linked immunosorbent assay (ELISA). Each sample of aqueous humor was tested in triplicate and the mean (pg/mL) and standard error of the mean (SE) were calculated. Relative amounts of TGFβ were determined in aliquot samples of aqueous humor by ELISA kits (Genzyme Corp, Boston, Mass.) and used according to the manufacturer’s instructions. Relative amounts of PGE2 were measured in samples from a total of 21 patients. Table 1 shows that the relative amounts of PGE2 were significantly higher in Molteno implant and trabeculectomy patients, compared with patients undergoing cataract extraction (p < 0.05, Mann-Whitney rank sum test). Relative amounts of TGFβ were measured in samples of aqueous humor from a total of 17 patients. Table 2 shows that the relative amounts of TGFβ in samples of aqueous humor from patients with Molteno implants were higher than those in samples from patients undergoing surgical trabeculectomy (p < 0.05, Mann-Whitney rank sum test). Intraocular pressure was significantly higher in patients with Molteno implants, compared with patients with glaucoma undergoing trabeculectomy (data not shown). There was a trend toward greater amounts of PGE2 and TGFβ in patients with higher intraocular pressures (data not shown). We have observed that samples of aqueous humor from patients with glaucoma contain raised amounts of PGE2 and TGFβ, which are higher in samples harvested from encysted blebs following Molteno implant surgery than in samples from patients with glaucoma undergoing trabeculectomy or from patients with cataract without glaucoma. We believe that these data are the first to suggest a direct relationship between raised intraocular pressure in glaucoma and production of PGE2 and TGFβ within the eye. We postulate that a sustained rise in intraocular pressure, particularly occurring in encapsulated blebs over glaucoma implants, stimulates the synthesis and secretion of TGFβ. This in turn stimulates the local production of PGE2, which, together with TGFβ, mediates ongoing inflammation, progressive fibrosis, an impaired outflow of aqueous humor, and a sustained rise in intraocular pressure. Taken together, these data lend further support to the concept that these substances contribute to the postoperative fibrosis that is the most common complication of filtration surgery for glaucoma and a major cause of treatment failure.