Ocular Tissue Concentrations Research Articles

Selenium Concentration in Ocular Tissues and Fluids

A simple, precise method for the analysis of selenium (Se) in ocular fluids and tissues using electrothermal atomic absorption spectroscopy is presented. Se concentrations ranged from 0.23 to 0.41 microgram/g wet weight in the cornea, iris, lens, and retina. The Se concentration in aqueous humor was 0.008 microgram/ml, thus much lower than that of plasma (0.21 microgram/ml). The concentration of protein in aqueous humor is about 1.0% of plasma. Since in plasma, Se is entirely bound to proteins, it is likely that the difference in Se concentration between plasma and aqueous humor reflects the relative distribution of protein between these fluids.

Hydrogen Peroxide in Anterior Segment Physiology

The role of hydrogen peroxide when it is physiologically produced or when it is applied externally to the eye is examined in this review. Three enzymes deal with the endogenously produced H2O2. They are catalase, superoxide dismutase, and glutathione peroxidase. These enzymes are present at different concentrations in ocular tissues and function most efficiently at different concentrations of H2O2. For H2O2 which contacts the external surface of the eye, the same enzymes also seem to act to metabolize the H2O2. In general the eye is more sensitive to changes in pH than to low concentrations of topically applied H2O2 at concentrations less than about 400 ppm. So, the small amounts of residual H2O2 which remain on contact lenses after disinfection in H2O2 solutions do not pose a great risk to the eyes.

Ocular biodistribution of clonidine after topical application with ophthalmic rods or solution.

We compared the ocular tissue and systemic blood distribution patterns of clonidine, an alpha 2-adrenergic agonist with ocular hypotensive activity, after topical application with ophthalmic rods or ophthalmic solution (eyedrops) in rabbits. We measured tissue concentrations at 0-240 minutes after administration with rods containing 5 micrograms, 10 micrograms, or 20 micrograms clonidine, or a 0.125% (62.5 micrograms) solution. The delivery efficiency of the rods was 65 - 71%. The rods and eyedrops had similar absorption and distribution patterns intraocularly and in systemic blood. Tissue concentrations of clonidine achieved were proportional to the dose delivered; peak ocular tissue concentrations were reached within 20 minutes (except for the lens). Clonidine concentrations were: tears greater than cornea greater than iris/ciliary body greater than or equal to aqueous humor greater than lens. We concluded that the ophthalmic rod offers a viable alternative to ophthalmic solution for the topical delivery of clonidine.

ARGININE-GLYCINE TRANSAMIDINASE IN BOVINE NEURORETINA AND PIGMENT EPITHELIUM

Gyrate atrophy (GA) patients exhibit chorioretinal degeneration and histologic muscle abnormalities. Due to autosomal recessive deficiency of ornithine aminotransferase they accumulate ornithine to levels, which are 10× normal and well above the K, of arginine-glycine transamidinase of rat kidney. We have previously shown inadequate synthesis of guanidinoacetate and low creatine concentration in plasma, urine, erythrocytes, and muscle tissue of GA patients. Supplementary creatine corrected the atrophic muscle pathology but the chorioretinal atrophy continued. We alleged that this discrepancy was due to ineffective transport of creatine across the blood-eye barrier and sought for synthesis of guanidinoacetate in ocular tissues. We developed a new assay for measuring the arginine-glycine transamidinase activity in bovine eye tissues with a new assay based on the detection of formed guanidinoacetate with alkaline ninhydrin reaction. We found transamidinase activity only in the neuroretina (NR) and retinal pigment epithelium (RPE). The pH optimum was 7.5 in NR and 7.9 in RPE and the apparent Km for arginine was 1.10 in NR and 4.96 mM in RPE, and for glycine 1.03 and 0.95 mM, respectively. Our results indicate that a potential energy-rich phosphagen compound can be formed in eye tissues. Reduction of the ornithine concentration in ocular tissues can possibly enable the transamidination also in gyrate atrophy.

Effect of different ointment bases on ocular disposition of ethylphenylephrine in rabbit eyes

The influence of vehicle composition on the ocular disposition of ethylphenylephrine, a mydriatic drug used for the treatment of wide-angle glaucoma, has been studied. The vehicles investigated consisted of a hydrocarbon base, an absorption base (10% lanolin in a paraffin base) and a water-soluble base (polyvinyl alcohol, PVA, 15% in water). The albino rabbit was chosen as the animal model. The disposition of the drug in conjunctiva, cornea, iris-ciliary body and aqueous humor of the rabbit was monitored at 1, 2 and 4 h post-installation using extraction technique. At the early time period (1 h post-administration) both oleaginous and water-soluble bases were judged to perform adequately in that they provided approximately the same drug concentrations in various ocular tissues at the aqueous vehicle. However, after 4 h, the oleaginous base provided the highest concentrations of drug in the conjunctiva. The water-soluble PVA formulation gave significantly lower levels in the conjunctiva and the cornea. At this same point, the absorption base containing lanolin produced the highest drug concentration in the cornea, iris-ciliary body and aqueous humor. Collectively, these data suggest that of the 3 bases studied, the oleaginous base and the absorption base show most promise as vehicles to extend the residence time of ethylphenylephrine in the eye. Obviously the final choice of vehicle will also be influenced by factors such as the physical and chemical stability of the drug in the formulation chosen and patient acceptance.

Elemental concentrations in ocular tissues of various species

An investigation was undertaken to expand the data base for elemental concentrations within eye tissues of different species. This report provides data on the distribution of calcium, copper, iron and zinc in human, dog, bovine, bird, amphibian and fish ocular tissues. The variation between different eyes of the same individual and different individuals was calculated for each metal. Elemental concentrations between the left and right eyes of an individual were usually closer in value than between two eyes of different individuals.

Intraocular Penetration of Topically Applied Lincomycin Hydrochloride in Rabbits

Ocular penetration of lincomycin hydrochloride in albino rabbits was determined by bioassay. On topical application, the frequency of multiple instillation of drops played an important role in producing therapeutic levels in the anterior chambers. Therapeutic levels were attained in the cornea, aqueous humor, and iris-ciliary body, with peak values occurring at 30 to 45 minutes. Varying the pH of the dosing solution did not change ocular absorption and distribution substantially. Removal of corneal epithelium, however, greatly enhanced absorption. Relative to clindamycin, lincomycin hydrochloride had longer onset of peak values and lower overall concentration in ocular tissues. Intravitreous injection of lincomycin hydrochloride produced therapeutic and steady levels of antibiotic in anterior chambers. Injection produced a concentration in aqueous humor twice that achievable topically. The major route of elimination from the posterior chamber was through retina-choroid.

Retinal toxicity of chlorpromazine in the rat

The retinal toxicity of chlorpromazine was studied in both albino and pigmented rats. In albino rats, the chronic administration of chlorpromazine (10 mg/kg po during 4 months) induced a large decrease in the amplitude of the electroretinogram (ERG) without detectable histological lesions. In pigmented rats (10 or 25 mg/kg for 6 months), despite a high concentration in ocular tissues, chlorpromazine did not induce functional ERG or histologic lesions. These data indicate that the ocular toxicity of chlorpromazine is not due to its affinity for melanin.

Antibiotic concentration in ocular tissues. Penicillin G and dihydrostreptomycin.

The total antibiotic concentration of penicillin G potassium (benzylpenicillin) and dihydrostreptomycin sulfate were determined in the ocular tissues of rabbits by radioactive tracer methods following systemic and subconjunctival administration. Free, unbound active antibiotic concentrations were determined by a modified disk diffusion assay. Both methods correlated well at concentrations greater than 200μg/gm wet tissue, but below this level the free antibiotic concentrations averaged 30% of the total for penicillin G and 75% for dihydrostreptomycin. After both systemic and subconjunctival administration, the free antibiotic levels in all tissues except lens and vitreous exceeded that in aqueous humor. Thus, the use of aqueous humor assays to determine the intraocular penetration of penicillin G and dihydrostreptomycin is not a valid indication of ocular tissue concentration.

Distribution of Sulfanilamide in the Ocular Fluids and Tissues After Local Application

SummarySulfanilamide was found to be present in significant concentrations in ocular tissues and fluids after its local application in powdered form into the conjunctival sacs of rabbits. No appreciable untoward reactions were encountered in the 19 rabbits studied. Local application of the drug for 1 hour did not result in an appreciable systemic absorption, since no sulfanilamide could be detected in blood samples, with two exceptions, or in ocular tissues and fluids of the untreated eyes of test animals.