Intraocular pressure increases with fenoldopam, but not nitroprusside, in hypertensive humans.

Fenoldopam mesylate stimulates adenyl cyclase in porcine ocular trabecular meshwork and raises intraocular pressure in humans. To clarify whether this results from direct activation of the dopamine-1 receptor or indirectly from baroreflex sympathetic stimulation after blood pressure reduction, intraocular pressure was measured in 14 patients with accelerated/malignant hypertension, randomized between intravenous fenoldopam or sodium nitroprusside. Intraocular pressure was measured with a Perkins tonometer, before and at the twentieth minute of each dose increment. In seven patients with a mean blood pressure of 232/131 mm Hg treated with fenoldopam, intraocular pressure increased in a dose-dependent fashion, from 16 +/- 1 to 20 +/- 2 mm Hg (p less than 0.005). In contrast, seven patients with a mean blood pressure of 225/134 mm Hg treated with sodium nitroprusside exhibited no change in intraocular pressure (15 +/- 1 versus 14 +/- 1 mm Hg) despite similar blood pressure reduction. Increases in heart rate were not significantly different. Rates of urinary excretion of norepinephrine plus epinephrine increased significantly relative to baseline (p less than 0.05) but were not different between groups. These data suggest that the increase in intraocular pressure with fenoldopam results from specific activation of the dopamine-1 receptor and is not caused by baroreflex sympathetic stimulation. Because dopamine-1 receptors may modulate intraocular pressure, dopamine-1 receptor blockers might be useful therapy for glaucoma.

Tissue plasminogen activator in the lens.

Biochemical analyses of normal lenses from monkey, dog and calf eyes revealed significant levels of tissue plasminogen activator (t-PA). By immunohistochemistry, a positive reaction product for t-PA was seen, in descending order of staining intensity, in the central epithelium, equatorial epithelium, superficial fibers of the anterior cortex, and anterior capsule of both human and monkey lenses. The possible functions of t-PA in the normal 801s include regulation of deformation that occurs in the anterior lens epithelium and fibers during the process of accommodation, and the destructive remodeling of the extracellular matrix including the lens capsule.

Distribution of tissue plasminogen activator in human and monkey eyes. An immunohistochemical study.

The authors examined various structures of human and rhesus monkey eyes for the presence of tissue plasminogen activator (t-PA) by using the peroxidase-antiperoxidase immunohistochemical technique with a monoclonal antibody specific for human t-PA. Positive staining for t-PA was observed both intracellularly and in the extracellular matrix of many tissues in both species. The tissues which stained intensely for t-PA included the corneal endothelium, corneal epithelium, trabecular meshwork, lens epithelium, peripheral vitreous, uveal tract, inner retina, and all vascular endothelia. The apparent minor difference in staining intensity between human and monkey eyes may be related to the time-dependent degradation of t-PA, to variations in the tissue content of t-PA, or to the difference in animal species. The discussion includes a consideration of the fibrinolytic activity of t-PA and of its emerging role in the destructive remodeling of the extracellular matrix in various ocular structures.

Tissue plasminogen activator in avascular tissues of the eye: a quantitative study of its activity in the cornea, lens, and aqueous and vitreous humors of dog, calf, and monkey.

We analysed the tissue plasminogen activator (TPA) content of the corneal epithelium, endothelium, and stroma and of the lens, as well as the aqueous and vitreous humors, in dog, calf, and monkey eyes. A quantitative estimation of the TPA activity in the corneal tissues by the [125I]fibrin-coated well assay showed similar levels of activity in the corneal epithelium, stroma, and endothelium. However, some differences were observed among the three mammalian species analysed. The values, expressed in urokinase (UK) units of activity per mg protein, ranged from 0.8 +/- 0.22 to 1.03 +/- 0.23 for the epithelium, 0.47 +/- 0.13 to 0.98 +/- 0.2 for the stroma, and 0.48 +/- 0.11 to 0.93 +/- 0.22 for the endothelium. The lens, the vitreous and the aqueous humor yielded low to negligible values. However, by using the enzyme-linked immunosorbent assay (ELISA) method, we detected an appreciable amount of TPA in the lens (9.49 +/- 1.5 ng TPA per ml lens), corneal epithelium (1.43 +/- 0.29 ng TPA per mg protein) and vitreous humor of the dog (5.71 +/- 0.61 ng TPA per ml vitreous humor) and of the calf (5.7 +/- 0.44 ng TPA per ml vitreous humor). Such discrepancies may reflect species-specific variation in the TPA content of the tissues and possibly the limitations of the techniques utilized, because of the problem related to cross-reactivity between the TPA of a given species and the antibody used in the assays.(ABSTRACT TRUNCATED AT 250 WORDS)