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Biomedical subjects

H F Edelhauser

Publications and source records attributed to H F Edelhauser.

28 records · Page 2Linked to original sources

The corneal penetration of trifluorothymidine, adenine arabinoside, and idoxuridine: a comparative study.

Trifluorothymidine (F3TdR) and idoxuridine (IDU) were observed to penetrate through the cornea from the epithelial side at a greater rate than adenine arabinoside (ARA-A) during in vitro corneal perfusions. Removal of the epithelium increased the rate of penetration of F3TdR and IDU by about twofold and the rate of ARA-A penetration by fivefold. The kinetics of antiviral penetration did not display saturation points at high antiviral concentrations, thus indicating that these three antiviral drugs penetrate the cornea by nonfacilitated diffusion. The sole breakdown product detected following F3TdR penetration in vitro, in situ, and in controls was 5 carboxy-2'-deoxyuridine (5-COOH-2'-dUd). The sole breakdown product isolated during ARA-A penetration experiments was hypoxanthine arabinoside (ARA-HX), and control experiments indicated that ARA-A was stable at pH 7.6. IDU was degraded to 2'-deoxyuridine (dUd) in control experiments, but during corneal penetration experiments IDU was degraded to a mixture of dUd and iodouracil (IU).

Animals

Oxygen consumption in the developing chick cornea.

Embryonic chick corneas at different stages of development were evaluated for O2 consumption. Some embryos were treated with thyroxine or thiouracil. In untreated animals, corneal QO2 (oxygen consumption/hr./mg. dry weight) decreased from 3.60 at stage 38 to 1.58 after hatching. The temperature coefficient Q10 increased from 1.55 at stage 40 to 2.03 after hatching. If O2 consumption is calculated as microliters of O2 consumed per hour per corneal pair, it increases between stage 38 (3.20) and hatched chicks (6.20) with a plateau between stages 40 and 45. Thiouracil treatment reduced O2 consumption by the cornea at stages 42 and 45, and thyroxine treatment elevated it at stage 40.

Age Factors

The role of thyroid hormone in the development of the chick corneal endothelium and epithelium.

Previous studies have established that thyroxine or thiouracil treatments affect the development of corneal transparency in the chick. The effects of these drugs on chick corneal epithelial and endothelial development were investigated because in the adult the integrity of these cell layers is necessary for the maintenance of corneal transparency. Chick embryos were treated with thiouracil or thyroxine at stage 36 or 38; the corneas were excised 2 to 12 days after treatment (between stages 38 and 45), and prepared for electron microscopy. The colloidal tracer ruthenium red was added during fixation to study epithelial and endothelial permeability and to stain the intercellular endothelial spaces. At all stages studied, the epithelium was impermeable to ruthenium red and this property was not affected by drug treatment. The epithelial barrier to this tracer is located in the outermost cell layer. The ease of penetration of ruthenium red through the endothelial intercellular spaces indicated the lack of zonular tight functions and the presence of gap functions in this cell layer. Thiouracil treatment delayed the development of the corneal epithelium so that at stage 45 it resembled epithelium from a normal embryo 3 stages younger. In normal animals, chick corneal endothelial development is characterized by an increasing degree of interdigitation of the lateral plasma membranes of adjacent endothelial cells with advancing embryonic age. Thiouracil treatment delayed this progressive development of adjacent cell membrane interdigitation. In contrast, thyroxine treatment accelerated the development of the lateral borders of the endothelial cells. It also appears that thyroid hormone can affect the development of the cell membranes of apposed cells in epithelium as well as the endothelium of the embryonic chick cornea.

Animals

Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium.

Widespread use of the mercurial-containing preservative thimerosal as an antibacterial agent in ophthalmic drugs and solutions warranted an investigation into its possible cytotoxic effects on the functional and ultrastructural integrity of the corneal endothelium. No changes in corneal thickness were observed during 5 hours' perfusion of the endothelium of rabbit and human corneas with 0.0001 and 0.0005 percent thimerosal in glutathione bicarbonate Ringer's solution (GBR). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) of the endothelium of the 0.0001 percent group revealed normal ultrastructure. SEM and TEM of the endothelium of corneas perfused with 0.0005 percent thimerosal for 5 hours revealed condensed mitochondria, cytoplasmic vacuoles, and cytoplasmic flaps at the apical end of the cellular junctions. Perfusion of higher concentrations (0.001 and 0.005 perecnt) of thimerosal in GBR resulted in increases in corneal thickness after 2 hours and irreversible ultrastructural damage to the endothelial cells by 5 hours. Corneas perfused with 0.01 and 0.1 percent thimerosal in GBR showed a rapid and immediate increase in corneal thickness and endothelial cell death and necrosis within 1 hour. It is postulated that the mercury in thimerosal becomes bound to the cell membrane protein sulfhydryl groups, causing an increase in cellular permeability; These results suggest that the prolonged exposure of the corneal endothelium to thimerosal in the accepted antimicrobial dosage of 0.005 to 0.001 percent may result in functional and structural damage to the endothelium.

Animals

Comparative toxicity of intraocular irrigating solutions on the corneal endothelium.

Isolated rabbit and human corneas were perfused in vitro with Plasma-lyte 148 solution and with a glutathione bicarbonate Ringer's solution. The corneal swelling rate and ultrastructure were compared to corneas perfused with three commonly used intraocular irrigating solutions. Corneas perfused with Plasma-lyte 148 swelled at a rate of 47 mu/gr and the endothelial cells separated from each other and showed extensive damage after three hours of perfusion. By comparison, corneas perfused with 0.9% NaCl increased in thickness by 98 mu/hr, lactated Ringer's by 39 mu/hr, balanced salt solution by 24 mu/hr, and glutathione bicarbonate Ringer's solution by 4 mu/hr. These results indicate that endothelial cell damage and increased corneal thickness observed during perfusion was related to the incomplete composition of 0.9% NaCl, Plasma-lyte 148, and lactated Ringer's and that endothelial cell damage can be prevented if the intraocular irrigating solution contains concentrations of inorganic and organic constituents that are similar to those in aqueous humor.

Animals

Effect of thiol-oxidation of glutathione with diamide on corneal endothelial function, junctional complexes, and microfilaments.

Intracellular-reduced glutathione (GSH) was removed by thiol-oxidation with diamide during in vitro perfusion of the corneal endothelium. By 15 min the normal mosaic-like pattern of the endothelial cells was disrupted by serpentine-like lines of cell separation at the cell juntions. After 45 min of perfusion, infividual clusters of cells formed cup-shaped islands. The resultant exposure of Descemet's membrane to the perfusion solution resulted in corneal swelling. Transmission electron microscopy revealed that the endothelial cells separated at the apical junctions and that the microfilaments in the apical cytoplasm of cells formed dense bands, whereas the other subcellular organelles were normal in appearance. The change in cellular shape may be due to loss of cellular adhesion which results in the condensation of the microfilaments or contraction of the microfilaments. The addition of glucose to the perfusate prevented the diamide effect, and the diamide effect could be reversed upon removal and perfusion of a glutathione bicarbonate Ringer's solution. These results suggest that the ratio of reduced to oxidized glutathione in the endothelial cells plays a role in the maintenance of the endothelial cell barrier function.

Animals

Intraocular irrigating solutions. Their effect on the corneal endothelium.

The effects of several intraocular irrigating solutions on the corneal endothelium of rabbit and monkey corneas were evaluated, utilizing a specular microscope perfusion system with both scanning and transmission electron microscopy. Corneas perfused with 0.9% sterile isotonic physiological saline swell at a rate of 60mum to 90mum/hr; endothelial cells separate from each other and show extensive degenerative changes. Corneas perfused with lactated Ringer solution swell at a rate of 37mum to 40mum/hr, and the endothelial cells show slower, but progressive degeneration. Corneas perfused with balanced salt solution swell at 24mum to 31mum/hr, and degenerative changes become severe only after two hours. Corneas perfused with Ringer solution containing bicarbonate, reduced glutathione, and adenosine do not increase in thickness, and there is minimal deterioration of endothelial ultrastructure for periods of up to six hours.

Animals

Effect of epinephrine on the corneal edothelium.

Intracameral epinephrine has been advocated for treatment of iris bleeding and inadequate pupillary dilatation during intraocular surgery. Commercial epinephrine 1:1000 with its preservative sodium bisulfite damaged corneal endothelial function and ultrastructure in rabbit and monkey eyes with sodium bisulfite the source of the damage. Endothelial damage can be prevented with a 1:5000 dilution of commercially available epinephrine in 0.1% sodium bisulfite or freshly prepared epinephrine bitartrate 1:1000 with a bicarbonate Ringers.

Animals

A comparison of corneal stromal edema induced from the anterior or the posterior surface.

BACKGROUND: Many differences between the anterior and posterior corneal stroma have been reported. The physiological and mechanical properties of the cornea are a summation of these properties across each of the corneal regions. This article investigates corneal stromal swelling that is experimentally induced through each surface. METHODS: Corneal stromal swelling was induced in human and rabbit corneas through either the anterior or posterior surface. The rate of stromal swelling was analyzed with a linear regression model. RESULTS: Swelling in the rabbit stroma was 3.65 x faster when induced through the posterior surface than through the anterior surface (p less than .0001), while the human stroma swelled 13.1 x faster through the posterior surface (p less than .0001). The hydration of the stroma increased during swelling through the posterior surface, but paradoxically decreased during swelling through the anterior surface. CONCLUSIONS: These experiments showed that stromal swelling occurs more rapidly through the posterior corneal surface than through the anterior surface. These results may have implications for the refractive surgeon performing laser ablative procedures on the anterior surface of the cornea.

Animals