Permeability Of Blood-aqueous Barrier Research Articles

A Study on Diurnal Fluctuation of Blood-Aqueous Barrier Permeability to Plasma Proteins

The diurnal change of blood-aqueous barrier permeability to protein molecules was investigated in 20 eyes of 10 normal volunteers. Simultaneous determinations of aqueous flow rate and the coefficient of entry into the anterior chamber (kin) for plasma protein were performed at different times of the day: (a) 0800 to 1100 hr: (b) 1900 to 2200 hr of the same day; (c) 0800 to 1100 hr of the next day; (d) 1400 to 1700 hr 1 week later; and (e) 0200 to 0500 hr of the following morning. Aqueous flow rate was determined by fluorophotometry and kin was calculated for each period from flow rate, plasma protein concentration, anterior chamber volume and aqueous protein concentration measured with a laser flarecell meter. Calculated values for kin did not fluctuate significantly among the periods, and there were no significant changes in anterior chamber volume or plasma protein concentration. Aqueous protein concentration and flow rate showed diurnal fluctuations, the patterns of which inversely corresponded to each other. It was concluded that permeability of the blood-aqueous barrier to protein remains fairly stable over a 24-hr period and the diurnal variation of aqueous protein concentration is mostly attributable to that of aqueous flow rate.

Evaluation of the blood-aqueous barrier permeability and aqueous flow by measurement of aqueous flare

Evaluation of the blood-aqueous barrier permeability and aqueous flow by measurement of aqueous flare

Effect of apraclonidine on blood-aqueous barrier permeability to plasma protein in man

Effect of a single instillation of 30 μl 0·5% apraclonidine on the coefficient of protein entry ( k in), a quantitative index of blood-aqueous barrier permeability, was determined in ten normal volunteers. Before and after administering the drug to one eye and the vehicle to the other eye of a subject, protein concentrations in the anterior chamber were measured using a laser flare-cell meter. One week later, aqueous flow rate was determined by fluorophotometry under the same experimental conditions. The k in was calculated from protein concentrations in the anterior chamber and the plasma and from aqueous flow rate based on a transfer equation formulating the kinetics of protein molecules in the anterior chamber. The k in showed a significant reduction at 3 and 4 hr after drug administration with a maximum decrease of 21 ± 6% (mean ± s.e., n = 10) at 3 hr, while the aqueous flow rate showed a significant reduction from 2 to 6 hr with a maximum decrease of 45 ± 5% at 3 hr. The results indicated that topical apraclonidine reduced both blood-aqueous barrier permeability as well as aqueous flow rate in humans. This dual reduction may relate to the efficacy of this drug in suppressing the post-laser intraocular pressure rises in patients.

Effect of topical phenylephrine on the permeability of the blood-aqueous barrier in man.

The effects of a single instillation of 5% phenylephrine on aqueous flow and the coefficient of protein entry into the anterior chamber, an index of blood-aqueous barrier permeability, were determined in normal human eyes by measuring fluorescein concentrations with a fluorophotometer and aqueous protein concentrations with a laser flare-cell meter. Both parameters showed a concomitant biphasic change. The coefficient of protein entry showed significant increases of 31 and 66% at 1 and 2 h, and a significant decrease of 18% at 3 h. Aqueous flow showed significant increases of 81 and 125% at 1 and 2 h and a significant decrease of 20% at 4 h. It is suggested that a change in the permeability of the blood-aqueous barrier might be related to changes in aqueous flow after topical phenylephrine.

PhXA34, a New Potent Ocular Hypotensive Drug

The prostaglandin analogue PhXA34 was tested in two studies in normal human eyes; 1, 3, and 10 micrograms of PhXA34 reduced the intraocular pressure by about 2, 3, and 4 mm Hg, respectively, 6 to 10 hours after a single topical dose. The only side effect observed was a slight conjunctival hyperemia after 10 micrograms of PhXA34. In a second study we determined the effect of 10 micrograms of PhXA34 once daily for 7 days on intraocular pressure, outflow facility, aqueous flow, blood-aqueous barrier permeability, ocular discomfort, and hyperemia. The mean intraocular pressure was below 9 mm Hg 12 hours post dose. About one third of the intraocular pressure reduction could be explained by increased outflow facility. Aqueous flow was unaffected. Treatment caused a 21% increase in aqueous fluorescence 1 hour after an oral dose of fluorescein. Mild ocular discomfort and some hyperemia were initially observed in half of the subjects, but frequency and magnitude of these side effects declined during the study.

Effect of Bunazosin Hydrochloride on Intraocular Pressure and Aqueous Humor Dynamics in Normotensive Human Eyes

We investigated the effects of topical administration of bunazosin hydrochloride, a new selective alpha 1-adrenergic antagonist, on intraocular pressure and aqueous humor dynamics in normal human eyes. In the single-dose study, all concentrations of bunazosin (0.025%, 0.05%, 0.1%, and 0.2%) significantly lowered intraocular pressure in a concentration-dependent manner. Administration of multiple doses of 0.1% bunazosin revealed no occurrence of tachyphylaxis after 1 week. Single application of 0.1% bunazosin had no significant influence on aqueous flow rate, tonographic outflow facility, or episcleral venous pressure, suggesting that bunazosin reduces intraocular pressure by increasing uveoscleral outflow. Aqueous protein concentration was found to be unaltered by bunazosin, indicating that blood-aqueous barrier permeability to protein molecules remained unchanged. We conclude that bunazosin may be a possible new antiglaucoma agent with a mechanism of action different from those currently in use for treating ocular hypertension.

Blood—Aqueous barrier breakdown associated with rhegmatogenous retinal detachment

We compared the integrity of the blood-aqueous barrier (BAB) between normal eyes and those with first-time rhegmatogenous retinal detachment (RRD) using the technique of anterior segment fluorophotometry. We found significantly greater anterior segment fluorescence in eyes with retinal detachment (p = less than .001) thereby demonstrating quantitatively for the first time that there is significant damage to the BAB associated with RRD. We have also shown that the BAB permeability returns to normal within two months of successful reattachment of the retina. The origin of this transient increase in BAB permeability is unknown but its severity and duration may well be of significance in the pathogenesis of complications associated with RRD such as uveitis, rubeosis and proliferative vitreoretinopathy.

Absence of Drug Effects on Rabbit Blood-Aqueous Barrier Permeability to Non-Electrolytes

The effects of either topical epinephrine, norepinephrine or pilocarpine upon the entry of non-transported radioactive solutes into the anterior or posterior chamber of pigmented rabbit eyes was examined after intravenous solute perfusion. Solutes employed were urea, thiourea, sucrose and inulin. They were infused at a rate that maintained constant plasma levels from 1 minute through 5 hours of intravenous perfusion. Anterior and posterior chamber samples were taken at either 5 minutes or 5 hours after infusion of solutes, but in either case at 1 hour after drug administration. Differences between the 5 minute and 5 hour data showed more solute entry with the passage of time, and differences were found between the rate of solute entry at both times based upon molecular size. However, while occasional statistically significant differences were found between certain drug treatments, no drug effects were noted on solute entry into the treated eye either when compared to the contralateral untreated eye or to a separate untreated control group.

Intraocular Irrigating Solutions and Permeability of the Blood-Aqueous Barrier

The effects of intraocular irrigating solutions on the blood-aqueous barrier were studied using rabbits injected with fluorescein isothiocyanate-labeled rabbit albumin. Two days after the injection, the anterior chamber was perfused for 121 minutes with one of the following solutions: normal saline, a commercially available citrate-acetate bicarbonate solution, or a glucose glutathione bicarbonate solution; the amount of fluorescein isothiocyanate-labeled rabbit albumin collected in the outflowing perfusate standardized to its plasma concentration was adopted as a blood-aqueous barrier permeability index. Of the three solutions, normal saline showed the highest permeability index and glucose glutathione bicarbonate solution showed the lowest. The effects of oxidized glutathione on the blood-aqueous barrier were also studied, using solutions containing various concentrations of oxidized glutathione. The permeability index for the solution containing 0.3 mmol/L of oxidized glutathione was significantly smaller than that for the solution without oxidized glutathione, suggesting that oxidized glutathione has a beneficial effect on the integrity of the blood-aqueous barrier.

Evaluation of Quality of Cataract Surgery. II. Inflammatory Response

Recent developments and refinements of surgical techniques of cataract extraction have established implantation of modern intraocular lenses (IOLs) as a safe effective procedure. The incidence of complications has decreased steadily and there is now a need to evaluate the quality of surgery. An important objective must be the prevention and control of the inflammatory response after IOL surgery. To evaluate and quantitate this inflammatory response we have performed anterior segment fluorphotometry in a series of sixteen patients submitted for intraocular implant surgery (eleven ordinary PMMA and five heparin-coated PMMA). Two methods for calculating blood-aqueous barrier permeability are compared, median percent difference and blood-aqueous barrier penetration ratio (30′). Our results show increased inflammatory response with increased duration of surgery ( P

Effects of subconjunctival 5-fluorouracil injections on the corneal endothelium and ciliary epithelium

The effects of 14 successive daily subconjunctival 5-fluorouracil (5-FU) injections on corneal endothelial and ciliary epithelial cells were studied in pigmented rabbits. A total of 100 microliters 5% or 1.25% 5-FU was injected subconjunctivally in one eye and vehicle solution was injected in the other eye. At 12 h or 14 days after the 14th and last injection, both eyes were processed for observation with scanning or transmission electron microscopy. In other groups of rabbits injected with 5% 5-FU, effects on the corneal thickness, corneal endothelial permeability, blood-aqueous barrier permeability, intraocular pressure and aqueous flow rate were also studied. In the fellow eyes and treated eyes examined 14 days after the last injection, no significant morphological changes were seen. In eyes examined 12 h after the last injection, the following findings were obtained. The corneal endothelial cells showed moderate cytoplasmic swelling and mitochondrial swelling and vacuolation. The changes were dose-dependent and most marked in the area near the injection site, whereas they were minimal in the area apposing it. In the ciliary body adjacent to the injection site, disarrangement of the basal infoldings of non-pigmented epithelial cells was seen in eyes injected with 5% 5-FU, whereas no significant change was observed in those injected with 1.25% 5-FU. However, the physiological parameters examined remained unaltered.

Quantitative assessment of the permeability of the rat blood‐retinal barrier to small water‐soluble non‐electrolytes.

1. The passive permeability of the blood-retinal barrier (b.r.b.) to the water-soluble non-electrolytes, sucrose and mannitol, was determined using a multiple time point-graphical approach as has been used in the assessment of blood-brain barrier (b.b.b.) permeability. 2. The calculated permeability surface area product for the b.r.b. for sucrose was 0.44 (+/- 0.081 S.E. of mean) X 10(-5) ml g-1 s-1 (n = 20) and for mannitol was 1.25 (+/- 0.30) X 10(-5) ml g-1 s-1 (n = 18). These values are similar and comparable to those found for the capillaries in the brain (P greater than 0.05) and significantly different from zero (P less than 0.01). 3. Data on the concentrations of sucrose in different parts of the eye show that the permeability of the blood-retinal barrier, rather than the more permeable blood-aqueous barrier permeability, was being measured by our technique.

Blood aqueous barrier permeability versus age by fluorophotometry.

Values of the diffusion coefficient into the anterior chamber and the blood aqueous barrier permeability as a function of age were determined by fluorophotometry in 58 healthy volunteers. The diffusion coefficient was calculated from aqueous fluorescein concentration and the time integral of non-protein bound fluorescein concentration in plasma. Blood-aqueous barrier permeability was calculated using diffusion coefficient values, the area of fluorescein inflow into the anterior chamber and anterior chamber volume. Values for diffusion coefficient as well as permeability were found to be independent of age between 13 y and 72 y (lin. corr. coeff. 0.2, p = 0.11) mean values were 4.7 .10(-4) min-1 +/- 1.5. 10(-4) SD and 15.4 nm/s +/- 4.8 SD, respectively. The difference between permeability values calculated from fluorophotometric scans at 30, 55 and 65 mins. after fluorescein injection was less than 5% and the 7 months reproducibility was within 15%. There was no significant correlation between simultaneously measured values of blood-retinal and blood-aqueous barrier permeability (lin. corr. coeff. 0.13, p = 0.4).

Effect of oxygen free radical products on rabbit iris vascular permeability.

Oxygen free radicals and their products are known to be elaborated by inflammatory cells during the 'respiratory burst'. Xanthine oxidase combined with hypoxanthine was injected into the anterior chamber of rabbit eyes. This combination is known to result in the production of oxygen free radicals. Iris fluorescein angiography performed 2 h and 24 h following injection of xanthine oxidase and hypoxanthine into the anterior chamber resulted in increased iris vascular permeability. The increased permeability was not modified by either of the prostaglandin inhibitors naproxen or aspirin nor by the free radical scavenger D-penicillamine. This study demonstrates that iris vascular permeability, and possibly blood-aqueous barrier permeability is increased following exposure to chemically generated oxygen free radicals. It is possible that the increased iris vascular permeability that occurs during ocular inflammatory processes may in part be mediated by oxygen free radical products. This model may be useful in developing therapeutic modalities directed at preventing the damaging effect of oxygen free radical products, and this may be of benefit in reducing the untoward effects of ocular inflammatory disorders.

The release of prostaglandins in human aqueous humour following intraocular surgery. Effect of indomethacin

Inflammatory reaction to ocular trauma is known to be related to prostaglandins. To further evaluate this phenomenon in human, PGE 1 and E 2 were measured by R.I.A. after silicic acid chromatography in aqueous humour of 26 patients before and 3 days after surgery for unilateral senile cataract (posterior chamber implant after extracapsular surgery). 13 out of these patients were treated with indomethacin by enteral route and 13 were not treated. PGE 2 levels increased in all non-treated patients from : m < 214 pg/ml before surgery, to 2666 ± 869 pg/ml (range : 257 - 8728) p < 0.001 after surgery. PGE 2 levels did not increase in indomethacin-treated patients. PGE 1 levels did not increase significantly in non-treated as in treated patients. 1) Intra-ocular surgery is followed in human by a constant increase of the only PGE 2 in the aqueous humour. 2) Indomethacin inhibits this increase. 3) The post-surgical increase in the permeability of blood-aqueous barrier appears to be related to a release of PGE 2 .

Immediate changes in protein-concentration in aqueous humor induced by intracapsular lens extraction in human eyes

In 71 patients that underwent intracapsular extraction of the cataract it was possible to collect aqueous humor (a.h.) in sufficient quantities at the beginning and at the end of the operation. Using radial immunodiffusion albumin, IgG and alpha-1-antitrypsin were measured in the samples. In secondary a.h. huge variations in the concentrations were apparent. The primary permeability of the blood-aqueous barrier and the time between sampling had no influence on the relative increase of the proteins. No statistically significant difference was found between normotensives and hypertensives and patients with or without myopia of higher degree (over 6 diopters). The relative increase of proteins according to their difference in molecular weight followed the same pattern as described for anterior uveitis. In patients for whom an enzymatic zonulolysis with trypsin was used for the extraction, the relative increase of IgG was significantly smaller than in those that did not receive this treatment (P less than 0.005). The possible sources contributing to the formation of secondary a.h. are discussed.