Anterior Chamber Aqueous Humor Research Articles

The Role of Biochemical Markers in Cataractogenesis. Literature Review

Lens transparency is determined by both cellular and subcellular levels of its organization. Abnormalities of its size, uniformity of shape and correct arrangement of the fibers lead to the scattering of light falling on the lens. At the same time, its normal transparent proteins turn into a cloudy, coagulated, insoluble form, and undergo denaturation. Therefore, the preservation of lens transparency is possible only with a certain chemical composition, achieved by a strict balance of all metabolism links. There are many different hypotheses about the disease etiology. It is known that intraocular fluid has a low content of proteins and an increased concentration of chloride-, lactate-, ascorbatanions in its composition, in contrast to blood plasma. It cannot be ruled out that this is due to the selective permeability of the blood–ocular barrier, which consists of non-pigmented epithelial cells of the ciliary body. In addition, the modification of molecular composition and constitutional imbalance in the intraocular fluid often causes of pathological processes development in the anterior segment of the eye. The blood-ocular barrier makes the eye an immune-privileged organ. However, many diseases, surgical interventions and eye injuries can lead to blood-ocular barrier damage. This causes to inflammatory effector cells and molecules inducing a cascade of reactions, which in turn results in irreversible fibrotic changes in the lens substance. In this regard, it becomes necessary to search for new reliable methods of determining the level of certain biochemical agents in intraocular structures, as well as establishing reference values for strategically important biomarkers of cataract development. This review presents modern views on biochemical markers imbalance in the anterior chamber aqueous humor and the lens, which contributes to its substance opacity.

Hypromellose improves mydriasis dynamics by phenylephrine in a rabbit experimental model

Purpose: to determine the main characteristics of the mydriatic effect of drug formulations of phenylephrine, containing and not containing hypromellose, hyaluronic acid as an auxiliary component, in a comparative in vivo study, as well as to study their local bioavailability and the effect on the mucous membrane of the eye. Materials and methods. The studies were carried out on 40 adult male Soviet Chinchilla rabbits. The research model involved the mydriatic impact and the local irritant effect of the drug when instilled into the awake rabbit’s conjunctival sac. The peak concentration of phenylephrine, which is part of all formulations studied, was determined in the aqueous humor of the anterior chamber of the animal's eye at the 5-minute point by high-performance liquid chromatography with tandem mass spectrometric detection. Results. A single instillation of 1 drop of a 2.5% solution of phenylephrine hydrochloride containing hypromellose as an excipient is superior in depth, rate of reaching the maximum mydriatic effect and its duration to the formulation that does not contain hypromellose as an excipient. Only in a few cases, drug formulations containing hypromellose caused an insignificant weak reaction of eyelid closure, in contrast to a moderate local irritant reaction of the rabbit's eye occurring when phenylephrine solution without hypromellose is instilled. Peak concentrations of phenylephrine in the aqueous humor of the anterior chamber of the eye determined 5 minutes after instillation of 1 drop of 2.5% phenylephrine solutions containing hypromellose significantly exceed those occurring when phenylephrine drugs of the same concentration that do not contain hypromellose are instilled. Conclusion. The inclusion of hypromellose as an auxiliary substance into the formulation of phenylephrine eye drops optimizes the pharmacodynamics and pharmacokinetics of the active substance due to faster penetration into the eye anterior chamber aqueous humor, increasing local bioavailability and prolonging the exposure time. In addition, the absence of a local irritating effect of such forms on the eye tissues may also be explained by the presence of hypromellose.

Some aspects of filtering bleb formation in patients with primary open-angle glaucoma after non-penetrating deep sclerectomy

PURPOSE. To determine the role of extracellular matrix (ECM), transforming growth factor β (TGF-β) and matrix metalloproteinase 9 (MMP-9) in the mechanisms of filtering bleb formation after non-penetrating deep sclerectomy (NPDS) in patients with primary open-angle glaucoma (POAG).METHODS. The study consisted of prospective examination of 65 patients with POAG operated by the NPDS method. Three groups were formed: group 1 — optimal hypotensive effect of NPDS (21 patients); group 2 — relative hypotensive effect (23 people); group 3 — absence of hypotensive effect (21 patients). During the postoperative period, the condition of the intraocular fluid outflow pathways was evaluated with ultra biomicroscopy, optical coherence tomography, level of intraocular pressure, as well as the concentrations of TGF-β and MMR-9 in the tear and aqueous humor.RESULTS. The anterior chamber aqueous humor was found to contain TGF-β in all patients with glaucoma. Group 1 was noted to have minimal initial TGF-β concentrations in the tear and aqueous humor, high MMR-9 level in the pre- and postoperative period. Sparse extracellular matrix was the substrate for the filtering blebs. Group 2 was revealed to have elevated initial concentrations of TGF-β in the tear and aqueous humor, extremely high level of MMP-9 in the aqueous humor, accumulation of MMP-9 in the tear after 2 weeks, and inhibition of TGF-β and MMP-9 two months after NPDS. In the early period, loci of rigid ECM were visualized in the filtering blebs, but functional outflow pathways were successfully formed by month two after additional therapy. Group 3 was established to have maximum TGF-β concentrations and low MMP-9 concentrations in the anterior chamber aqueous humor, a decrease in tear MMP-9 after two weeks, and inhibition of TGF-β and MMP-9 two months after NPDS. In the early postoperative period, the filtering blebs were based on rigid ECM, by month two there was scar deformation of the outflow pathways.CONCLUSION. The important conditions for the formation of functional filtering blebs after NPDS are the structural organization of temporary ECM of the filtering blebs in the early postoperative period and the timely degradation of ECM components with predominant concentration of MMR-9 over TGF-β.

Investigation of biomarkers in the anterior chamber aqueous humor and the vitreous body in patients with neovascular glaucoma and diabetes mellitus

PURPOSE. To study possible biomarkers of proliferative diabetic retinopathy complicated by neovascular glaucoma and hemophthalmos located in the aqueous humor of the anterior chamber of the eye and the vitreous body, and to evaluate their role in the pathogenesis of pathological neovascularization in diabetes mellitus.METHODS. Samples were taken from the anterior chamber aqueous humor of 7 patients with type 2 diabetes mellitus and operated neovascular glaucoma (Ahmed valve), as well as from the vitreous body of the same patients who underwent vitrectomy after drainage surgery due to long-term total hemophthalmos. The comparison group consisted of patients without diabetes mellitus, who also had aqueous humor samples taken from the anterior chamber of the eye and vitreous. Concentration of markers was assessed by multiplex immune analysis.RESULTS. A significant increase in the levels of selected markers relative to the control group (patients without diabetes mellitus) was found in the aqueous humor of the anterior chamber and the vitreous body. The concentration of some cytokines differed significantly in the experimental and control groups suggesting the possibility of their evaluation for early detection of a more severe course of diabetic retinopathy.CONCLUSION. The obtained results expand the knowledge about the pathogenesis of neovascular glaucoma and confirm the importance of further study of the immunological aspects of pathological neovascularization in diabetes mellitus. This allows us to take a fresh look at the role of biomarkers in the process and indicates their connection with the activation and support of the pathological chain of the process of new vessels formation.

Hemodialysis Effect on the Composition of the Eye Fluid of Cataract Patients.

Numerous reports have proven that dialysis patients experience disturbances in the levels of elements in biological fluids. Disturbances in the homeostasis of essential elements or the appearance of highly toxic elements are serious problems also in clinical ophthalmology. The purpose of this study was to investigate the influence of hemodialysis (HD) on the elemental composition of anterior chamber aqueous humor (AH) in patients undergoing cataract surgery. The study involved 22 patients. The control group enrolled 16 patients (age 75.68 ± 9.67, female 54.55%, male 45.45%) with cataract and normal kidney function (control), and the second group included six patients (age 70.33 ± 12.74, female 33.33%, male 66.67%) with cataract undergoing HD treatment. The elements quantification was established using an inductively coupled plasma optical emission spectrometer (ICP-MS). In the eye fluid of dialysis patients, there were increased levels of manganese (Mn) and mercury (Hg) and decreased levels of vanadium (V) and zinc (Zn). In addition, a statistically significant increase in the Hg/Zn and Hg/selenium (Se) ratios and a lowering of the iron (Fe)/Mn ratio were observed in the studied group in comparison to the control. The obtained results indicated the need for Zn and Se supplementation in order to eliminate the hazards caused by Hg toxicity. A lower level of V in the eye fluid of dialysis patients may have a positive effect on maintaining a calcium and phosphorus homeostasis. Our study gives a deep insight into changes of elements concentrations in AH induced by HD.

INFLAMMATION MARKERS in CORNEA PENETRATING WOUND

Research purpose was to study the presence and local levels of inflammation markers (cytokines) in the anterior chamber and blood in patients with penetrating corneal wound. Material and methods. Thirty patients aged 24-55 years (mean age 31.2 ± 0.34 years) with penetrating corneal wound for 1-2 days from the moment of trauma were examined. The control group consisted of 30 patients aged 38-55 years (mean age 43.9 ± 0.21 years) hospitalized for surgical treatment - phacoemulsification of cataract without concomitant pathology. Anterior chamber aqueous humor sampling was made in all patients: in the experimental group during the primary surgical debridement of cornea penetrating wound, in the control group - during the phacoemulsification of cataract. Peripheral blood sampling also was made just before the operation. IL-1β, IL-1Ra, IL-4, IL-6, IFN-α, TNF-α levels, measured by EIA, and the expression of the herpes viruses (cytomegalovirus and herpes simplex virus I and II), measured by PCR, were studied. Results and discussion. The study showed that all the investigated cytokines were in the blood and in the AC aqueous humor of examined patients. High concentration of IL-1Ra, IL-1β, TNF-a и IL-4 was in the experimental group, as compared to control group. Systemic innate immunity was activated in the experimental group and was significantly higher in the C-reactive protein index in patients of the experimental group as compared to control group. Conclusion. An acute period of eye injury is accompanied by a local and systemic increase in proinflammatory and anti-inflammatory cytokines, which indicates an imbalance in the regulation of immune inflammation, as the basis for the implementation of immuno-inflammatory complications.

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity.

Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms involved in the etiology of these defects have not been fully characterized. Previously, we observed PCG-like phenotypes in transgenic mice that lack functional angiopoietin-TEK signaling. Herein, we identified rare TEK variants in 10 of 189 unrelated PCG families and demonstrated that each mutation results in haploinsufficiency due to protein loss of function. Multiple cellular mechanisms were responsible for the loss of protein function resulting from individual TEK variants, including an absence of normal protein production, protein aggregate formation, enhanced proteasomal degradation, altered subcellular localization, and reduced responsiveness to ligand stimulation. Further, in mice, hemizygosity for Tek led to the formation of severely hypomorphic Schlemm's canal and trabecular meshwork, as well as elevated IOP, demonstrating that anterior chamber vascular development is sensitive to Tek gene dosage and the resulting decrease in angiopoietin-TEK signaling. Collectively, these results identify TEK mutations in patients with PCG that likely underlie disease and are transmitted in an autosomal dominant pattern with variable expressivity.

DRUG DELIVERY: FROM A CONTACT LENS TO THE ANTERIOR CHAMBER

Mathematical models to describe drug concentration profiles of topi- cally administered drug in the anterior chamber aqueous humor have been proposed by several authors. The aim of this paper is to present a mathematical model to predict the drug concentration in the anterior chamber when a therapeutical contact lens with the drug is entrapped in nanoparticles is used. Diseases of the anterior segment of the eye are mostly treated by topical ocular administration in the inferior fornix of the conjunctiva. Nevertheless the procedure is extremely inefficient because when a drop (50 to 100�l per drop) is instilled in the eye, the ophthalmic drug has a short residence time in the conjunctival sac, less than 5 minutes, and only 1−5% of the applied drug penetrates the cornea reaching the intraocular tissues. The biovailability tends to be low and depends on the precorneal fluids dynamics, drug binding to tear proteins, conjunctival drug absorption, tears turn over, resistance to corneal penetration, nasolachrymal drainage, metabolic degradation and non-productive absorption. The absorption and the efficacy of the instilled drug can be increased by altering its formulation and/or by changing the local conditions. In the last years many researchers have proposed the use of therapeutic contact lenses to increase the ocular bioavailability of ophthalmic drugs. The first attempt to increase the residence time of the ophthalmic drug was the use of soaked contact lenses. The lens is hydrated once placed on to the cornea and releases the drug until an equilibrium is reached between drug concentration in the contact lens and in the conjunctival sac; the maximum

Measurement of AQCmax of Five Different Ophthalmic Solutions and Discussion of Its New Application

After measuring the pharmacokinetic parameters of five fluoroquinolone ophthalmic solutions, we utilized the obtained indices to try to predict the clinical effects of antimicrobial ophthalmic solutions and apply the characteristics to the index for inhibition of resistant bacteria. Each ophthalmic solution was instilled in white rabbit eyes 3 times every 15 min and the anterior chamber aqueous humor was collected 10, 30, 60, 120, and 240 min after instillation. Drug concentrations were measured by high-performance liquid chromatography (HPLC) to determine the maximum aqueous concentration (AQCmax) of each drug by using a 1-compartment model. Moxifloxacin (MFLX) had the highest AQCmax, 9.04 microg/mL, among the five drugs, followed by levofloxacin (LVFX, 2.65 microg/mL), gatifloxacin (GFLX, 1.26 microg/mL), ofloxacin (OFLX, 0.89 microg/mL), and tosufloxacin (TFLX, 0.42 microg/mL) in descending order of AQCmax. Furthermore, the AQCmax/MPC (mutant prevention concentration) against Staphylococcus aureus was 15.07 and 1.06 for MFLX and LVFX, respectively. The AQCmax/MPC against Streptococcus pneumoniae was 18.08 and 1.15 for MFLX and LVFX, respectively. From these results, we can expect that the MFLX ophthalmic solution will be a sufficiently effective therapeutic agent in the treatment of eye infection, prevention of postoperative endophthalmitis, and prevention of drug resistance.

Modeling the drug transport in the anterior segment of the eye

Purpose The aim of the present work is the development of a simple mathematical model for the time course concentration profile of topically administered drugs in the anterior chamber aqueous humor and investigation of the effects of various model parameters on the aqueous humor concentration of lipophilic and hydrophilic drugs. Method A simple pharmacokinetic model for the transient drug transport in the anterior segment has been developed by using the conservation of mass in the precorneal tear film, Fick's law of diffusion and Michaelis–Menten kinetics of drug metabolism in cornea, and the conservation of mass in the anterior chamber. An analytical solution describing the drug concentration in the anterior chamber has been obtained. Result The model predicts that an increase in the drug metabolic (consumption) rate in the corneal epithelium reduces the drug concentration in the anterior chamber for both lipophilic and hydrophilic molecules. A decrease in the clearance rate and distribution volume of the drug in the anterior chamber raises the aqueous humor concentration significantly. It is also observed that decay rate of drug concentration in the anterior chamber is higher for lipophilic molecules than that for hydrophilic molecules. Conclusion The bioavailability of drugs applied topically to the eye may be improved by a rise in the precorneal tear volume, diffusion coefficient in corneal epithelium and distribution coefficient across the endothelium anterior chamber interface, and by reducing the drug metabolism, drug clearance rate and distribution volume in anterior chamber.

Reversible visual disturbance due to cryptococcal uveitis in a non-HIV individual

A 52-year-old man without underlying diseases visited a local hospital with symptoms of memory deficit and mild headache. Radiological examination of the brain with computed tomography (CT) revealed hydrocephalus. Etiology was not revealed by cerebrospinal fluid (CSF) analysis and a ventricular-atrial (V-A) shunt was installed. The patient had congestion and dacryorrhea of the right eye and uveitis was diagnosed three months after placement of the V-A shunt. The serum cryptococcal antigen (CrAg) tested positive at a titration of 64 times. Additionally, samples of the right eye anterior chamber aqueous humor (ACAH), cerebrospinal fluid (CSF) and prostate fluid were positive for Cryptococcus antigen at a titration of 128 times. In addition, Cryptococcus neoformans var. grubii was isolated from the peripheral blood, CSF and ACAH, resulting in a diagnosis of disseminated cryptococcosis. Fluconazole (FLCZ) at 800 mg/day was administered for the first two days, followed by a 400 mg/day maintenance dose. After six months of treatment, his visual power recovered. This is a rare case of disseminated cryptococcosis involving uveitis, which was successfully treated by FLCZ. Disseminated cryptococcosis should be considered in cases with mild symptoms and V-A shunt installation for hydrocephalus.

Concentration of Transforming Growth Factor β2 in Aqueous Humor

The total transforming growth factor (TGF) β₂ concentration in the anterior chamber aqueous humor of 96 cataract patients with ages ranging from 17 to 88 years was measured using ELISA to investigate the changes that occur with age, difference of axial length, difference of localization of opacification of the cataractous lens and complications with other eye diseases. It was found that the total TGF-β₂ concentration (1) decreases with age, (2) shows slight changes with axial length, (3) has slight changes with difference of localization of opacification, (4) is significantly high in patients with concurrent open-angle glaucoma (p < 0.05), (5) is high in patients with complicating diabetes who have undergone panretinal photocoagulation for diabetic retinopathy (p < 0.05) and (6) is low in patients with atopic cataracts. There have been several reports on point 4 above, but none to date of the other points. These findings provide useful information on the intraocular activity of TGF-β₂.

Disorders of the blood-aqueous barrier after phacoemulsification

To determine the status of blood-aqueous barrier after small incision phacoemulsification with implantation of foldable intraocular lens. The blood-aqueous barrier status in 64 eyes of 60 patients who underwent cataract surgery was examined using a laser flare cell meter. The protein level of anterior chamber aqueous humor was evaluated by measurement of the flare value preoperatively and postoperatively. The mean preoperative flare intensity was (6.94 +/- 0.34) photon counts/ms, which increased to (26.27 +/- 1.37), (13.96 +/- 1.05), (9.07 +/- 0.43) and (7.16 +/- 0.27) photon counts/ms on days 1, 7, 30 and 90 after the surgery, respectively. Significantly statistical differences on flare values were found between preoperative data and those on days 1, 7 and 30 after surgery. The blood-aqueous barrier was recovered on day 90 postoperatively. The variables such as age, gender, eye (left/right) had no influence on the flare value. Patients with iris prolapse had a higher flare value at day 1 and day 7 after the surgery. Blood-aqueous barrier after phacoemulsification with implantation of intraocular lens can be measured quantitatively by the laser flare cell meter. The blood-aqueous barrier disorders can be recovered shortly after phacoemulsification.

Studies on the mechanism of action of timolol and on the effects of suppression and redirection of aqueous flow on outflow facility

Long-term use of drugs that suppress aqueous humor formation, such as timolol and dorzolamide, or that redirect aqueous humor outflow from the trabecular meshwork, such as prostaglandin F 2α analogues, could cause underperfusion of the trabecular meshwork and a secondary decrease in outflow facility. We investigated the mechanism of suppression of aqueous humor formation by timolol in monkey eyes by measuring aqueous humor ascorbate levels. We also determined whether suppression of aqueous humor formation with and without redirection of aqueous humor away from the trabecular meshwork could lead to a subsequent reduction in outflow facility, and whether this reduction was correlated with increased fibronectin levels in anterior chamber aqueous humor. In cynomolgus monkeys, unilateral dose/aqueous humor formation response curves were generated for timolol, dorzolamide, and a combination of timolol+dorzolamide. Aqueous humor formation and/or outflow facility were measured in both eyes after approximately four days, four weeks and seven weeks of twice daily treatment with 3·5 μg timolol+1·0 mg dorzolamide to one eye and 30% DMSO to the other. In some monkeys, 5 μg prostaglandin F 2α-isopropyl ester (PG) was added to timolol+dorzolamide for 4-week treatments. Intraocular pressure and corneal endothelial transfer coefficients ( k a) were also measured at four weeks. Aqueous humor fibronectin levels were determined in four monkeys after approximately 9·5 weeks of timolol+dorzolamide treatment. Aqueous humor formation, intraocular pressure, and aqueous humor ascorbate levels were also determined in rhesus monkeys at baseline and after a single unilateral topical administration of 25 μg timolol. Compared to baseline for the same eye, aqueous humor formation was significantly decreased in treated eyes at all doses of timolol and at 1·8 and 4 mg dorzolamide. Compared to the opposite control eye, aqueous humor formation was lower in treated eyes after 3·5 and 5 μg timolol and after all doses of dorzolamide. Aqueous humor formation after treatment with 3·5 μg timolol+1·0 mg dorzolamide was decreased in treated vs. control eyes, after four days and was suppressed in both treated and control eyes after four weeks of treatment, but not when PG was added. There was no difference in k a values with or without the addition of PG. Intraocular pressure was significantly lower in both treated and control eyes vs. baseline after ∼6·5 weeks treatment with timolol+dorzolamide when taken 2 hr after the last dose and after ∼3·5 weeks treatment with timolol+dorzolamide+PG when measured 6 hr after the last dose. Outflow facility after treatment with timolol+dorzolamide was unchanged after four days, tended to be lower in the treated vs. control eyes after four and seven weeks, and was significantly lower in treated vs. control eyes after four weeks treatment with timolol+dorzolamide+PG (0·352±0·052 vs. 0·515±0·096 μl min −1 mmHg −1, p≤0·02). Both treated vs. control eye aqueous humor fibronectin levels were below the level of detection for our assay (0·01 μg ml −1). The 25 μg timolol dose decreased ipsilateral, but not contralateral intraocular pressure (12·6±1·7 vs. 15·2±0·9; p<0·05) and aqueous humor formation (1·40±0·08 vs. 2·03±0·09 μg ml −1, p≤0·01). There was no difference in anterior chamber ascorbate levels in treated vs. control eyes or compared to their respective baselines. Our findings indicate that timolol affects neither ciliary epithelial transport of ascorbate nor aqueous fibronectin levels. Our data also indicate that decreasing aqueous humor formation over a period of time can lead to reduction in outflow facility, particularly when combined with therapy that redirects aqueous from the trabecular meshwork. Future intraocular pressure-lowering therapies for glaucoma may better be directed at enhancing flow through the trabecular pathway as opposed to decreasing aqueous humor formation or rerouting aqueous humor away from the trabecular meshwork.

Vacuoles in the AcrysofTM Intraocular Lens as Factor of the Presence of Serum in Aqueous Humor

Objective: Acrysof™ (Alcon) foldable lenses (IOLs) have been shown to be highly biocompatible and exhibit a low incidence of posterior capsular opacification. However, minute vacuoles or ‘glistenings’ have been observed in some Acrysof IOLs. The clinical relevance of vacuole formation is presently unclear. To help clarify the influence of factors present under in vivo conditions on vacuole formation, the present experimental study examines the influence of aqueous humor components on the occurrence of vacuoles in Acrysof IOLs. Methods: A total of 12 sterile Acrysof IOLs (Alcon, MA60BM) were incubated at body temperature (37°C) for 3 or 6 months in anterior-chamber aqueous humor with or without human serum. The center portion was cut from two unconditioned, unhydrated, sterile control IOLs and the 12 conditioned IOLs and examined using light microscopy for vacuole formation. A third unconditioned, hydrated control IOL was examined using light and scanning electron microscopy. Measures: The incidence of vacuoles was quantified by two independent investigators using light microscopy. After hydration with balanced salt solution, the surface quality of a control IOL was examined using scanning electron microscopy. Results: The control IOLs exhibited no or very few vacuoles. Scanning electron microscopy revealed that the control IOLs had normal surface texture without any surface vacuoles. IOLs that had been conditioned in aqueous humor without serum exhibited no great increase in the number of vacuoles, whereas IOLs conditioned in aqueous humor with serum exhibited a greater number of vacuoles that increased over time. Conclusions: The number of vacuoles increases with incubation time in aqueous humor containing serum. The addition of serum increased the proportion of lipids and proteins in the solution, which also occurs with a breakdown in the blood-aqueous barrier. The results of the present study point to a physiological factor that may lead to vacuole formation in IOLs and may aid clinicians in identifying risk factors involved in the formation of vacuoles.

Effects of serotonergic compounds on aqueous humor dynamics in monkeys

Purpose. The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. Methods. We determined the effect of a single topical unilateral 300 µg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 µg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). Results. Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of ~70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. Conclusion. The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.

Effects of topical PGF2 alpha on aqueous humor dynamics in cynomolgus monkeys.

Single topical applications of prostaglandin F2 alpha (PGF2 alpha) tromethamine salt to living cynomolgus monkey eyes reduced intraocular pressure (IOP). Twice daily topical application was far more effective, so that after the 7th 50 micrograms or 100 micrograms dose on day 4, IOP fell 40-50%, to 8-10 mm Hg. Following twice daily application of 50 or 100 micrograms for greater than 3 days: (1) no increase in total outflow facility could be demonstrated by 2-level constant pressure perfusion or Schiotz tonography; (2) no decrease in aqueous humor formation rate could be demonstrated by fluorophotometry--rather, aqueous flow may have increased; (3) anterior chamber aqueous humor protein concentration was unaltered, but entry of intravenously injected fluorescein into the cornea and anterior chamber tended to increase; (4) there was a weak but sometimes statistically significant miosis of up to approximately 0.5 mm. We conclude that in the cynomolgus monkey: (1) PGF2 alpha is a potent ocular hypotensive agent with only very weak miotic and blood-aqueous barrier-disrupting effects; (2) the ocular hypotensive action of PGF2 alpha is definitely not due to increased conventional outflow facility or decreased aqueous production, but probably to increased uveoscleral drainage of aqueous humor.

Source of subretinal fluid on the basis of ascorbate analyses.

Biochemical analyses of subretinal fluid revealed a consistently high ascorbate level in the subretinal fluid of patients with rhegmatogenous retinal detachment. The average values and SDs of ascorbate in anterior chamber aqueous humor, subretinal fluid, and blood were 14.7 +/- 1.8, 27.4 +/- 2.1, and 1.8 +/- 0.2 mg/dL, respectively. The ascorbate concentration in subretinal fluid was always higher than that in aqueous humor. The high ascorbate level in subretinal fluid led to the hypothesis that aqueous humor contributes to the formation of subretinal fluid. Presumably and constant absorption of subretinal fluid by the choroid directs a portion of the aqueous humor from the posterior chamber into the subretinal space. The posterior movement of aqueous humor causes reduced ascorbate concentration in the anterior chamber and relative hypotony of eyes with rhegmatogenous retinal detachment. Closing the retinal break results in an interruption of the posterior movement of aqueous humor and rapid absorption of the remaining subretinal fluid by the choroid.

Osmotic relations between the fluids of the rabbit eye.

SummaryThe osmotic activity of serum and the fluids and humors of the eye was measured (37°) using a vapor pressure osmometer. Vitreous humor was found to be isosmotic to serum. Aqueous humor obtained immediately postmortem was approximately 11 mOsmolal hyperosmotic to serum. On comparison of anterior chamber aqueous humor and vitreous humor obtained from the same eyes, the mean difference was 10.6 ± 8.8 mOsmolal (p < 0.001) aqueous hyperosmotic.The fluid secreted from the anterior surface of rabbit lenses incubated in silicone oil was collected by low speed centrifugal separation. The osmolality of this fluid from 24 lenses was 262.4 ± 16.5 mOsmolal. The fluid secreted by the lens is significantly hyposmotic to each of the other fluids (p < 0.005).The author is very grateful to Carolyn McDonald and Jacqueline Wright for their technical assistance. This work was supported by NIH grant NINDB#1979 (EY00202-13).

The biological activity of catecholamines in rabbits at various intervals after irradiation

The biological activity of catecholamines isolated from the anterior chamber's aqueous humor at various periods of radiation sickness was assessed. For this purpose a study was made of the disturbances in the work of the isolated frog heart and the changes occurring in desympathized pupil diameters in response to catecholamine administration. On the basis of the data obtained it is shown that catecholamines are biologically active during the whole period of radiation sickness.