The pharmacokinetics of a new antiglaucoma drug, latanoprost, in the rabbit

Latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2alpha-1-isopropyl ester) is a unique prostaglandin analogue developed for the treatment of glaucoma. To investigate the pharmacokinetics, tritium-labeled latanoprost was administered topically on the eyes of rabbits and intravenously. About 7.7% of the applied dose was found in the cornea at 15 min after the drug administration. The following Cmax and elimination half-life (interval 1-6 hr) values of the total radioactivity in the eye tissues were found: aqueous humor, 0.09 ng eq/ml and 3.0 hr; anterior sclera, 1.49 ng eq/mg and 1.8 hr; cornea, 1.59 ng eq/mg and 1.8 hr; ciliary body, 0.39 ng eq/mg and 2.8 hr; conjunctiva, 1.41 ng eq/mg and 1.4 hr; and iris, 0.39 ng eq/mg and 2.1 hr. Latanoprost was rapidly hydrolyzed, and most of the radioactivity found in the aqueous humor, anterior eye tissues, and plasma corresponded to the pharmacologically active acid of latanoprost. The initial plasma elimination half-life of the acid of latanoprost was 9.2 +/- 3.2 min after iv and 2.3 +/- 1.9 min after topical administration on the eyes. The plasma clearance of the acid of latanoprost was 1.8 +/- 0.3 liters/hr.kg, and the volume of distribution was 0.4 +/- 0.1 liter/kg after iv administration. Based on the retention times on HPLC and GC-MS, the main metabolite in urine and feces was identified as the 1,2,3,4-tetranor metabolite of acid of latanoprost. This acid existed in equilibration with the corresponding delta-lactone. The AUC of radioactivity in the eye tissues was approximately 1000 times higher than in plasma AUC. The recovery of radioactivity was complete.     

Ocular pharmacokinetics of orally administered azithromycin in rabbits

Azithromycin was orally administered to Dutch-belted rabbits following extracapsular lens extraction in one eye. At various times the animals were sacrificed, and serum and ocular tissues were obtained for drug level determination by HPLC-EC. Following a single dose, peak levels of drug in ocular tissues were measured within 8 hours (cornea > 0.5 micrograms/g [15mg/kg]; > 1.5 micrograms/g [3Omg/kg]). Highest levels were obtained in iris and ciliary body ( > 15 micrograms). Measurable tissue levels persisted for at least 120 hours. Trough levels increased proportionately during drug multiple dose administration. Five days following five daily 15mg/kg doses, corneal levels exceeded 0.5 micrograms/g, and iris and ciliary levels were higher than 15 micrograms/g. Aqueous humor and serum levels were equivalent. Vitreous humor levels, though higher than aqueous humor, were consistently < 1 microgram/ml. Extracapsular cataract extraction did not significantly affect drug uptake.     

Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.     

Absorption of sodium diclofenac after ocular administration in rabbit

Sodium diclofenac (DCF, CAS 1507-79-6) is a non-steroidal anti-inflammatory drug whose activity is mainly due to an inhibitory effect on the synthesis of the prostaglandins. At present, a tendency towards its topical use in the treatment of the inflammatory state of the anterior segment of the eye as an alternative to the steroid drugs is observed. The pharmacokinetics of DCF was studied in rabbits by assessing the ocular and systemic absorption of DCF after administering DCF eye drops. The chromatographic methods available were not sensitive enough to quantify the extremely low drug concentrations which appeared in the biological fluids after ocular treatment. For this reason, the concentrations of DCF in plasma and aqueous humor were evaluated by a coupled liquid chromatography/gas chromatography (LC/GC) method. DCF was absorbed well through the cornea with the aqueous humor concentration peak being 757.8 ng/ml at 120 min. This good ocular absorption of DCF was confirmed by the concentrations observed in plasma. The presence of tramazoline (TMZ, CAS 74195-73-6) in the eye drops increases the levels of DCF in aqueous humor.     

Experimental and clinical study of antibiotics administered intravitreally in endophthalmitis

The concentrations of gentamicin and cefotaxime (claforan) in the humor of the anterior chamber and vitreous body of the eye were estimated in the study on the pharmacokinetics of the antibiotics in rabbits. The antibiotics were administered intravitreally in single doses. It was shown that the residence time of the antibiotics in the therapeutic concentrations in the eye cavity was 48 hours. Cefotaxime proved to be the most efficient agent in the prevention and treatment of postoperative endophthalmitis.     

Effects of Al3+ and Be2+ ions combined with NaF on ciliary process adenylyl cyclase activity and aqueous humor dynamics in the rabbit eye

PURPOSE: The activity of Al3+, Ga3+, and Be2+ ions in the presence of NaF to directly activate G-proteins was investigated by their potentiative effect on forskolin (FSK)-activated adenylyl cyclase in rabbit ciliary process membranes and their effects on aqueous humor dynamics in vivo. METHODS: Adenylyl cyclase (AC) was determined by radiometric conversion of ATP to cAMP by the particulate fraction of rabbit ciliary processes. Intravitreal injections of sterile solutions of analytical grade salts were made into the center of the vitreous in a volume of 20 microliters. Intraocular pressure, aqueous humor flow, and uveoscleral outflow measurements were made by pneumatonometry, fluorophotometry, and fluorescein-dextran method, respectively. Outflow facility was determined by tonography in the intact eyes and by two-level constant pressure perfusion in cannulated eyes. RESULTS: Both Al3+ (EC50, 40 mumol/l) and Be2+ (EC50, 11 mumol/l) in the presence of 0.5-2 mM NaF activated the stimulatory G-protein Gs. Ga3+ was ineffective and did not antagonize the activation by Al3+. Intravitreal injections of Al3+ (1 mumol/eye) or Be2+ (0.5 or 1 mumol/eye) had no significant intraocular pressure (IOP) effect, nor did 1.5 or 3 mumol/eye of NaF, but when either cation was injected together with NaF, IOP decreased by up to 40% for up to 140 hr. At the time of maximum IOP effect (72 hr) aqueous humor flow determined by fluorophotometry was decreased in BeCl2+ NaF-treated eyes by 40% relative to BeCl2-treated eyes; however, tonographic facility of outflow was unaffected. Uveoscleral flow was also decreased by 38% in BeCl2+ NaF treated eyes. CONCLUSIONS: These findings support the hypothesis that Gs activation of ciliary process adenylyl cyclase decreases aqueous humor formation rate in rabbit eyes, and that activation of G-proteins mediates contraction of ciliary muscles causing a decrease of aqueous humor outflow via the uveoscleral route. The results suggest that G-proteins putatively involved in trabecular facility changes are less sensitive to activation by BeF3- than are other parameters of aqueous humor dynamics.     

Identification of a neuropeptide and neuropeptide-processing enzymes in aqueous humor confers neuroendocrine features to the human ocular ciliary epithelium

The ocular ciliary epithelium, the site of aqueous humor secretion in the mammalian eye, is believed to play a key function in signaling mechanisms that regulate the rate of secretion, and thus intraocular pressure. One possible way of mediating these signaling functions is through neuropeptides and hormones secreted into the aqueous humor and acting on target tissues. We recently identified a cDNA clone sharing 100% identity with carboxypeptidase E (CPE), a neuropeptide-processing enzyme. Utilizing polymerase chain reaction, we further identified and characterized another processing enzyme, the peptidylglycine alpha-amidating monooxygenase (PAM), and the neuropeptide secretogranin II, a molecular marker restricted to neuroendocrine tissues. Using specific probes, we found that the nonpigmented ciliary epithelial cells express CPE, PAM, and secretogranin II mRNA, and protein. We also found that CPE and secretogranin II are abundant in aqueous humor. Treatment of cultured ciliary epithelial cells with veratridine and phorbol ester up-regulates CPE and PAM. Secretogranin II was found to be induced by veratridine, whereas phorbol ester had little effect, suggesting different mechanisms for secretion. The results demonstrate that secretogranin II, CPE, and PAM represent a specialized group of neuropeptide and neuropeptide-processing enzymes secreted by the ciliary epithelial cells which may confer to them neuroendocrine functions in cell-cell communication or cell signaling.     

Aqueous humor dynamics in beagle dogs with caffeine-induced ocular hypertension

In order to investigate the possible mechanisms for caffeine-induced ocular hypertension, the intraocular pressure (IOP) and the outflow through the trabecular meshwork were measured in beagle dog eyes after dosing with intravenous caffeine (30 mg/kg) alone or in combination with the topical beta-blocker befunolol [applied as 100 microliters of a 1% (w/v) solution] which inhibits aqueous humor formation in the ciliary body. Intravenous injections of caffeine significantly increased the IOP at 0.25 and 1 hr after a single dose. The ocular hypertension recovered within 2 hr following dosing. Over time, there were no differences in the outflow between the caffeine and control groups. The instillation of befunolol lowered outflow and produced ocular hypotension. The levels of the IOP and outflow in dogs treated with caffeine and befunolol in combination were almost the same as those in dogs treated with befunolol alone. Single-dose and combination-dose studies demonstrate that intravenous caffeine increases the IOP in normal beagle dogs possibly by increasing aqueous humor formation and not by the inhibition of aqueous humor drainage through the trabecular meshwork.     

The "agnosia" syndrome]

Studies have been made on the activity of glycosidases from eye tissues of developing chick embryos and adult hens. The enzymes of carbohydrates metabolism (hyaluronidase, beta-glycosidase and beta-galactosidase) from the sclera, cornea and ciliary body were examined. It was demonstrated that the distribution of glycosidases in different tissues of the eye is not identical. The activity of beta-glycosidase and beta-galactosidase in all the tissues of 14-day embryos is higher than in adult hens; sharp reduction of the activity was observed at the stage of eye opening. The activity of hyaluronidase in the sclera and cornea of chick embryos is maintained at a low level up to the stage of eye opening, being subjected to minor changes.     

A release mechanism for stored ATP in ocular ciliary epithelial cells

Purines can modify ciliary epithelial secretion of aqueous humor into the eye. The source of the purinergic agonists acting in the ciliary epithelium, as in many epithelial tissues, is unknown. We found that the fluorescent ATP marker quinacrine stained rabbit and bovine ciliary epithelia but not the nerve fibers in the ciliary bodies. Cultured bovine pigmented and nonpigmented ciliary epithelial cells also stained intensely when incubated with quinacrine. Hypotonic stimulation of cultured epithelial cells increased the extracellular ATP concentration by 3-fold; this measurement underestimates actual release as the cells also displayed ecto-ATPase activity. The hypotonically triggered increase in ATP was inhibited by the Cl--channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) in both cell types. In contrast, the P-glycoprotein inhibitors tamoxifen and verapamil and the cystic fibrosis transmembrane conductance regulator (CFTR) blockers glybenclamide and diphenylamine-2-carboxylate did not affect ATP release from either cell type. This pharmacological profile suggests that ATP release is not restricted to P-glycoprotein or the cystic fibrosis transmembrane conductance regulator, but can proceed through a route sensitive to NPPB. ATP release also was triggered by ionomycin through a different NPPB-insensitive mechanism, inhibitable by the calcium/calmodulin-activated kinase II inhibitor KN-62. Thus, both layers of the ciliary epithelium store and release ATP, and purines likely modulate aqueous humor flow by paracrine and/or autocrine mechanisms within the two cell layers of this epithelium.     

Glucose biosensors based on oxygen electrode with sandwich-type membranes

Cyclosporine is an important tool for the therapy of immunological diseases of the cornea and conjunctiva, as well as the treatment of patients with high-risk corneal grafts. However, potentially severe systemic side effects are disadvantageous. The purpose of our study was to determine if topical ocular application leads to about the same concentrations in ocular tissues as systemic application. Therefore, the concentration of cyclosporine in conjunctiva, aqueous humor and blood was measured by radioimmunoassay in six patients with systemic administration of cyclosporine and ten patients who received one drop of topical cyclosporine 2% four times prior to cataract surgery. All patients with systemic application showed measurable concentrations of cyclosporine in blood, as did four patients in the group receiving topical cyclosporine. There was no significant difference between both groups concerning cyclosporine concentration in aqueous humor. The level of cyclosporine in the conjunctiva was significantly higher after topical application (P < 0.02). In conclusion, therapy with cyclosporine eye drops results in levels in the conjunctiva and aqueous humor that are comparable to or even higher than those after systemic application if the last application was no more than 18h prior to the measurement. Therefore, topical ocular application of cyclosporine, which reduces or eliminates the drug's systemic side effects, can be used to induce local immunosuppressive activity, particularly in the treatment of superficial immunological diseases and after limbal allograft transplantation.     

Influx of immunoglobulins from the vascular compartment into a grafted cornea

PURPOSE: To determine the effect of a fresh corneal wound or a healed corneal scar on the immunodiffusion of immunoglobulins into the cornea. METHODS: F344 rats were immunized with human serum albumin (HSA) 1 week before an autologous rotational keratoplasty of the right cornea or 1 year after an autograft was performed. One group of rats also was treated with gentamicin-dexamethasone ointment in the grafted eye for 1 week after transplantation to reduce the postsurgical inflammatory signs. A serum sample was drawn every week and booster injections with HSA were given after 2 and 3 weeks. At various times after immunization, groups of rats were killed, blood and aqueous humor samples were taken, and the corneas of both eyes were removed. The corneas were divided into the graft or a 3-mm central button and the peripheral rim and weighed. The anti-HSA titer was determined in serum, aqueous humor, and both parts of the corneas. RESULTS: Up to 5 weeks after transplantation, the grafted cornea contained more anti-HSA immunoglobulins than did the control eye. One year postgrafting, no difference was seen. In the first weeks after keratoplasty, influx of anti-HSA from the peripheral into the central cornea was, however, neither obstructed nor enhanced. CONCLUSIONS: Surgical trauma in itself causes increased influx of anti-HSA immunoglobulins into the cornea. Within the cornea, a wound or a scar does not appear to be a barrier for centripetal immunoglobulin diffusion.     

The immunology of corneal graft rejection

Corneal transplantation is the most successful of organ transplants due to the fact that the eye is an immunologically privileged site, and the cornea is an immunologically privileged tissue. The factors responsible for this include presence of the blood-aqueous barrier, the avascularity of the cornea, the absence of classic antigen-presenting cells (APCs) in the central cornea, inhibitory factors in the aqueous humor, the phenomenon known as anterior chamber-associated immune deviation (ACAID), and the intraocular expression of Fas ligand. Loss of ocular immune privilege can occur with breaching of the blood-ocular barrier, corneal neovascularization, migration of classic APCs to the center of the cornea, loss of inhibitory factors in aqueous humor, abrogation of ACAID, and loss of Fas ligand expression within the anterior chamber. The purpose of this review is to analyze these events and how they relate to corneal graft rejection. A discussion on future research and therapeutic modalities is provided.     

Cytoskeleton and tissue origin in the anterior cynomolgus monkey eye

We studied cytoskeletal proteins and other markers for embryologic origin in the outflow pathways of the aqueous humor, cornea, sclera, and ciliary muscle of the cynomolgus monkey. The corneal endothelium and trabecular cells stained with markers for vimentin, smooth muscle cell alpha-actin, F-actin, spectrin, vinculin, and talin. The endothelium of Schlemm's canal stained with markers for vimentin, spectrin, and F-actin. These results suggest that trabecular cells are a kind of myofibroblast and support the belief that the endothelial cells of Schlemm's canal are vascular in origin. Fibrillary staining with antibodies to vimentin, spectrin, neurofilament protein, and glial acid fibrillary protein was observed along and between the ciliary muscle cells. Cells in the deep sclera adjacent to the supraciliary space stained with antibodies to smooth muscle alpha-actin, alpha-vinculin, talin, and desmin. These cells may anchor ciliary muscle cells into the sclera or may be developmental remnants of ciliary muscle cells. Leu 19 immunoreactivity was found in the corneal endothelium, in all trabecular cells, in ciliary muscle cells, and in keratocytes and fibroblasts in the superficial part of the cornea and sclera. All of these cells are therefore likely to express neural cell adhesion molecules indicating neuroectodermal origin.     

Limiting life support. Experiences with a special protocol

PURPOSE: This study aimed to quantitate and compare the concentration of vascular endothelial growth factor (VEGF) in aqueous humor samples from patients with neovascular glaucoma (NVG), primary open-angle glaucoma (POAG), and cataract, as well as in serum samples of healthy human subjects. METHODS: The authors collected aqueous humor samples by using their previously published technique of limbal paracentesis. The authors determined the concentration of VEGF by using a competitive enzyme immunoassay system and four-parameter logistic curve fitting and performed statistical analysis by using the Mann-Whitney-Wilcoxon test. RESULTS: The authors detected VEGF in 12 of 12 samples from patients with NVG (mean +/- standard error of the mean, 29.267 +/- 7.350 ng/ml), 15 of 28 samples from patients with POAG (0.726 +/- 0.204 ng/ml), 4 of 20 aqueous humor samples from patients with cataract (0.257 +/- 0.043 ng/ml), and 16 of 16 human serum samples (20.246 +/- 1.568 ng/ml). The mean concentration of VEGF in aqueous humor of patients with NVG was 40- and 113-fold higher than that in patients with POAG and cataract, respectively, and the difference was statistically significant (P < 0.01). The VEGF level in patients with POAG was elevated compared with that in patients with cataract (P < 0.05). Although the mean concentration of VEGF in aqueous humor of patients with NVG was approximately 1.45-fold higher than that in serum, the difference was not significant (P > 0.05). CONCLUSION: The authors' findings show that patients with NVG had a significantly increased level of VEGF in the aqueous humor and implicate VEGF as an important factor in the pathogenesis of intraocular neovascularization in these patients. The authors discuss the possible role of the ciliary epithelium, in addition to retina, in the production of VEGF and the complementary function of basic fibroblast growth factor and other growth factors.     

Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas

PURPOSE: To determine the distribution of matrix metalloproteinase-1 (MMP-1) in the uveoscleral outflow pathway and other anterior segment tissues of normal human eyes. METHODS: Normal human eyes were fixed in methacarn and sectioned and immunostained using a specific polyclonal antibody to MMP-1. Immunoreactivity was visualized using diaminobenzidine. To compare the staining intensity in various tissues, the mean optical density within the ciliary body, mid-iris stroma, iris root, uveal trabecular meshwork, cornea, and sclera was determined using imaging densitometry. To determine the cellular distribution of MMP-1 in ciliary muscle, additional sections were double-immunostained using antibodies to MMP-1 and calponin. These sections were examined by confocal laser scanning microscopy. Specificity of the antibody to MMP-1 in ocular tissues was confirmed by western blot analysis with uveal tract homogenates. RESULTS: Moderate-to-strong MMP-1 immunoreactivity was observed in ciliary muscle, iris, sclera, corneal endothelium, and ciliary nonpigmented epithelium. Lighter immunoreactivity was observed in corneal epithelium, blood vessels, trabecular meshwork, Schlemm's canal, and associated collector channels. Confocal microscopy showed that ciliary muscle MMP-1 was primarily inside ciliary muscle cells. Densitometry showed that net optical density was approximately fivefold greater in ciliary muscle, iris root, and sclera than in trabecular meshwork. CONCLUSIONS: MMP-1 was prominently identified in regions of the anterior segment of normal human eyes associated with the uveoscleral outflow pathway and in the iris, corneal endothelium, and ciliary nonpigmented epithelium. These data support the hypothesis that MMP-1 activity is involved in regulating uveoscleral outflow facility.     

Pharmacokinetics of sparfloxacin in the serum and vitreous humor of rabbits: physicochemical properties that regulate penetration of quinolone antimicrobials

We have used a recently described animal model to characterize the ocular pharmacokinetics of sparfloxacin in vitreous humor of uninfected albino rabbits following systemic administration and direct intraocular injection. The relationships of lipophilicity, protein binding, and molecular weight to the penetration and elimination of sparfloxacin were compared to those of ciprofloxacin, fleroxacin, and ofloxacin. To determine whether elimination was active, elimination rates following direct injection with and without probenecid or heat-killed bacteria were compared. Sparfloxacin concentrations were measured in the serum and vitreous humor by a biological assay. Protein binding and lipophilicity were determined, respectively, by ultrafiltration and oil-water partitioning. Pharmacokinetic parameters were characterized with RSTRIP, an iterative, nonlinear, weighted, least-squares-regression program. The relationship between each independent variable and mean quinolone concentration or elimination rate in the vitreous humor was determined by multiple linear regression. The mean concentration of sparfloxacin in the vitreous humor was 59.4% +/- 12.2% of that in serum. Penetration of sparfloxacin, ciprofloxacin, fleroxacin, and ofloxacin into, and elimination from, the vitreous humor correlated with lipophilicity (r2 > 0.999). The linear-regression equation describing this relationship was not improved by including the inverse of the square root of the molecular weight and/or the degree of protein binding. Elimination rates for each quinolone were decreased by the intraocular administration of probenecid. Heat-killed Staphylococcus epidermidis decreased the rate of elimination of fleroxacin. Penetration of sparfloxacin into the noninflamed vitreous humor was greater than that of any quinolone previously examined. There was an excellent correlation between lipophilicity and vitreous entry or elimination for sparfloxacin as well as ciprofloxacin, fleroxacin, and ofloxacin. There are two modes of quinolone translocation into and out of the vitreous humor: diffusion into the eye and both diffusion and carrier-mediated elimination out of the vitreous humor.     

Toxic shock syndrome after mastoidectomy

PURPOSE: To evaluate the effect of topical aqueous humor suppressants on the absorption of intravitreal perfluorocarbon gases. METHODS: Sulfur hexafluoride or perfluoropropane was injected intravitreally in five rabbits. Time to gas disappearance was measured in eyes treated with topical aqueous humor suppressants and in those not treated. RESULTS: The mean time (+/- SD) to disappearance of 0.4 cc of sulfur hexafluoride was 5.6 +/- 0.9 days, which was prolonged by 43% to 8.0 +/- 0.7 days with topical aqueous humor suppressants (P = .009). The mean time (+/- SD) to disappearance of 0.2 cc of perfluoropropane was 18.4 +/- 1.9 days, which was prolonged by 55% to 28.6 +/- 2.7 days with topical aqueous humor suppressants (P = .009). CONCLUSION: Aqueous suppressants prolong sulfur hexafluoride and perfluoropropane intravitreal gas bubble duration in rabbits.     

Changes of some physicochemical parameters of gas exchange in aqueous humor of rabbits during treatment of experimental uveitis

PURPOSE: To evaluate the usefulness of some parameters of the aqueous humor: pH, pO2 (oxygen pressure), pCO2 (carbon dioxide pressure) and HCO3- concentration in the diagnosis of uveitis. Changes of these parameters following conventional treatment and cryotherapy have also been investigated. MATERIAL AND METHOD: We used 40 grey rabbits (weighing 2.5-3.0 kg). Uveitis was evoked by intravitreal injection of 5 mg of animal albumin. Cryotherapy was performed by transconjunctival, quintuple cryoapplication (30 s) over ciliary body. Samples of aqueous humor were collected 6, 12, 24 and 48 hours after albumin injection. pH, pO2, pCO2 values and HCO3- concentration were determined using Astrup microanalyser. RESULTS: Parameters of aqueous humor, especially pH, pCO2 and HCO3- turned out to be fairly sensitive indicators reflecting the natural history of experimental uveitis. Cryotherapy characteristically modulates the pH, pCO2 and HCO3- values in the anterior chamber. CONCLUSIONS: We came to the conclusion that monitoring of these parameters may give some important information about the intensity of the course of uveitis and the influence of the treatment. Normalisation of the values usually parallels clinical improvement.