The pathophysiological effects of nitrogen mustard on the rabbit eye. I. The biphasic intraocular pressure response and the role of prostaglandins

Abstract

Topical application of 1·0% nitrogen mustard (NM) to the rabbit eye was found to cause a rapid rise in intraocular pressure (IOP) reaching a peak within 40 min, followed by a period of normo- or hypotension. At the same time, miosis and a gradual rise in aqueous flare occurred, but white cells (WBCs) were not seen in the anterior chamber. A second rise in IOP occurred 3–12 hr following NM application. After 12 hr, the soluble protein concentration in the aqueous humor had increased from a control value of 0·47±0·05 to 16·1±0·6 mg/ml, the combined prostaglandin (PG) F 2α and PGE concentration from 0·42±0·08 to 2·7±0·4 ng/ml, and the WBC count from 0 to 845±273 WBCs/μl. Intraperitoneal indomethacin treatment did not affect the initial IOP rise, but it completely blocked the second hypertensive phase and reduced the aqueous flare, cellular response, aqueous humor PG levels, and duration of miosis. In 12 out of 15 retrobulbar EtOH “denervated” eyes, the initial rise in IOP after NM application was completely blocked, but the second rise in IOP and the associated signs of uveitis were not inhibited. A combination of indomethacin treatment and “denervation” completely blocked both hypertensive phases and partially inhibited the aqueous flare and cellular response during the first 12 hr. These findings indicate that only the initial NM-induced ocular irritative response, in particular the first hypertensive phase, is mediated by a neural mechanism, and that PGs play an important role in the second hypertensive phase and associated ocular inflammation which peaks 6 to 12 hr after topical NM application.