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The aqueous humor is secreted by the ciliary epithelium, a bilayered syncytial epithelium comprising a pigmented (PE) cell layer abutting the stroma and a nonpigmented (NPE) cell layer facing the aqueous phase. As in other epithelia, secretion depends on the transfer of solute, with water passively following. Na+, K+, and Cl- enter the syncytium principally through a Na(+)-K(+)-2Cl- symport, diffusing to the aqueous surface of the NPE cells. The Na+, K+, and Cl- are secreted into the aqueous humor through the Na+/K+ exchange pump, K+ channels, and Cl- channels, respectively. Na+ is also secreted between the cells in response to a small transepithelial potential. The K+ channels are critical not only for K+ release but also for hyperpolarizing the membrane, providing an electrical driving force for Cl- secretion. Some of the K+ channels are Ca2+ sensitive and can be activated by Ca2+ entry through T- and L-type Ca2+ channels. The roles of the ciliary epithelial nonselective and Na+ channels are less clear. This review describes the ion channels thus far identified in the ciliary epithelium in terms of the activation and inactivation of their macroscopic currents, the open probabilities and conductances of the single channels, and their locations and regulation. The review relates each class of channel to known families of channels and indicates how those channels can contribute to the secretion of the aqueous humor.
In vivo perfusion of the anterior chamber of normal rhesus monkeys with pooled rhesus aqueous humor gives an initial total facility of 0.48 +/- 0.08 (+/-S.E.) microliter/min/mm Hg. With continued intermittent perfusion for 2 hr this value increased only slightly to 0.57 +/- 0.10 microliter/min/mm Hg. Perfusion of the paired eyes of the same monkeys with glutathionebicarbonate Ringer's solution gives an initial total facility of 0.55 +/- 0.08 microliter/min/mm Hg. This value increased to 1.21 +/- 0.15 microliter/min/mm Hg with continued intermittent perfusion. Thus aqueous is a satisfactory perfusate for experiments requiring prolonged stability of the eye, but glutathione-bicarbonate Ringer's solution is not a satisfactory substitute perfusate. Neither addition of physiologic amounts of ascorbic acid to the buffered salt solution nor careful modification of the pH of the solution to the physiologic level prevented the increase of total facility it produces when used as a perfusate. A reversible, fast-phased small-magnitude increase in total facility was noted in eyes perfused with either perfusate. It is speculated this is caused by neural mechanisms for intraocular pressure control.
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The aqueous humor and serum of patients with various ocular diseases were analyzed for the occurrence of rheumatoid factor or immune complexes. Rheumatoid factor was detected by its direct agglutinating activity on IgG-coated particles (latex) and immune complexes were detected by their ability to inhibit exogenous rheumatoid factor or the subunit q of the first component of complement (Clq). Rheumatoid factor or inhibitory activity were found in the aqueous humor of nine of 11 patients with Fuchs' syndrome. In some patients who were examined two or three times, agglutination alternated with inhibition. Among 13 patients with endogeous uveitis, five had either agglutinating or inhibitory activities in their aqueous humor. The tests were also positive in the aqueous humor of three of seven patients with choroidal melanoma. A high titer of rheumatoid factor was found in the aqueous humor in an accidentally perforated eye that resulted in sympathetic ophthalmitis. No inhibitory or agglutinating activity was detected in the aqueous humor of 20 patients with senile immature cataract.
The aqueous humor supplies nutrients to the nonvascularized cornea, lens, and trabecular meshwork. A number of tissue growth factors have been detected in this fluid. The composition of these proteins changes dramatically with different ocular conditions, such as inflammation and glaucoma. In this review, an overview of new findings regarding effects of aqueous humor growth factors is given. Our main emphasis is on the regulation of the avascular anterior eye compartment, the possible role of growth factors in the pathogenesis of glaucoma, and the importance of growth factors for the special immunosuppressive status of the anterior chamber.
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PURPOSE: To assess aqueous humor dynamics in mouse eyes. METHODS: Aqueous humor dynamics of NIH Swiss White mouse were assessed with an injection and aspiration system, using fine glass microneedles. Intraocular pressure (IOP) was measured by a microneedle connected to a pressure transducer. Episcleral venous pressure (EVP) was measured by gradually lowering intracameral pressure until blood reflux into Schlemm's canal was observed. Outflow facility (C) was determined based on constant pressure perfusion measurements obtained at two different IOPs. Aqueous volume (V(a)) was determined by direct measurement of aspirated aqueous humor. Aqueous humor production (F(a)) was measured by the dilution method with rhodamine-dextran. Conventional and uveoscleral outflow (F(c) and F(u), respectively), as well as the turnover rate of aqueous humor, were also calculated. RESULTS: IOP and EVP were 15.7 +/- 2.0 and 9.5 +/- 1.2 mm Hg, respectively (n = 20). F(a) was 0.18 +/- 0.05 microL/min (mean +/- SD; n = 8). C was 0.0051 +/- 0.0006 microL/min per mm Hg (n = 8). Estimated F(c) and F(u) were 0.032 and 0.148 microL/min, respectively. F(c) was 18% of F(a). F(u) was 82% of F(a). V(a) was 5.9 +/- 0.5 microL (n = 8). The calculated turnover rate of aqueous humor was 2.5%. CONCLUSIONS: The mouse eye has similar aqueous production and aqueous humor turnover rate as the human eye. The presence of both conventional and uveoscleral outflow suggests that the mouse is a useful model system for further investigations of the biology of aqueous dynamics.
The purpose of this study was to validate an analytical method for the determination of bendazac and its main metabolite 5-hydroxybendazac in aqueous humor. The method was validated with rabbit aqueous but it can be used also for human aqueous since no differences between the two matrices were observed. The results obtained indicate that the method is reproducible, accurate, precise, sensitive and specific for the measurement of bendazac and 5-hydroxybendazac in the aqueous humor. Therefore it can be considered suitable for experimental purposes, drug monitoring and adequate for regulatory requirements.
Topical prostaglandins (PGs) are very effective at reducing intraocular pressure (IOP) in a variety of animals and in humans with relatively few side effects. The mechanisms of action of several PGs, their prodrugs and analogues have been studied in rabbits, cats, monkeys and humans. PGF2 alpha and its analogues evaluated in monkeys include PGF2 alpha-tromethamine salt, PGF2 alpha -isopropylester (-IE), S-1033, PhXA34, PhDH100A and latanoprost (PhXA41). Aqueous flow and outflow facility are either increased or remain unchanged by these agents. PGF2 alpha-IE, PHXA34, PhDH100A and latanoprost increase uveoscleral outflow, accounting for most of the IOP reduction. PGA2 in cats increases aqueous flow and outflow facility, but it reduces IOP primarily by stimulating uveoscleral outflow. The PGD2 analogue BW245C is unique in that it is the only PG that decreases aqueous flow. Mechanistic studies in humans have been performed with PGF2 alpha -IE, unoprostone, PhXA34 and latanoprost. In two clinical studies with latanoprost, a significant increase in uveoscleral outflow was found which, as in animals, accounts for most of the IOP reduction. A slight but inconsistent increase in outflow facility may also be involved. The doses tested had minimal effects on the permeability of the blood-aqueous barrier (BAB). In vitro studies of human tissue have been conducted to elucidate the PG effect on outflow facility and uveoscleral outflow. Studies of isolated human anterior segment preparations show that PGE2 increases outflow facility whereas PGF2 alpha has no measurable effect on this parameter. Studies of human ciliary muscle cells in tissue culture indicate that PGs may directly modulate extracellular matrix metabolism, which may be related to the increased uveoscleral drainage. This review summarizes in vitro and in vivo studies of the effects of PGs on aqueous humor dynamics and BAB integrity in humans, cats and monkeys.
Blood, aqueous humor and cataracts obtained from an Indian population were analyzed for ascorbic acid content. While the concentrations of ascorbic acid in the blood and cataracts were similar in patients with cortical and nuclear cataracts, the level of this nutrient was lower in the aqueous humor of patients with cortical cataracts. This suggests a sluggish transport of ascorbate from the blood to the aqueous humor in the latter group. It is possible that this lower level of ascorbate might be one of the factors participating in cataractogenesis. The lower aqueous ascorbate in the group with the cortical cataracts could not be accounted for by any dietary deficiency of this nutrient. Hence, it appears metabolically related.
An aqueous humor draining device, with size comparable to that of the Krupin tube, was constructed by using poly-HEMA material. Deposits were found on the surface of poly-HEMA when contacted in vitro with the aqueous humor of the rabbit's eye. A fibrous structure, probably composed of proteins and other macromolecules, developed on poly-HEMA surface in 15 days after the draining device was implanted into the rabbit's eye. The draining device was still in function 250 days after its implantation. SEM analysis of the retrieved poly-HEMA draining device indicated that the poly-HEMA tube opening was not blocked by any substance. These results suggest that poly-HEMA could be used as a biomaterial for construction of the aqueous humor draining device to relieve the intraocular pressure of glaucoma patients. Its long-term application awaits further investigation.
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