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Biomedical subjects

L Cheeks

Publications and source records attributed to L Cheeks.

36 records · Page 2Linked to original sources

Ocular blood flow and vascular permeability in endotoxin-induced inflammation.

Blood flow was measured in several tissues of the rabbit eye following intravitreal injection of a dose of endotoxin that induces an inflammatory response. In separate experiments, the vascular permeability of the inflamed eye was estimated by iris fluorescein angiography and by measuring protein influx into the aqueous humor. The effect of topical corticosteroid treatment upon blood flow and vascular permeability was also measured. Following intravitreal endotoxin injection, minor changes in blood flow occurred in retina and optic nerve head. Marked changes were observed in blood flow in iris, ciliary processes, and choroid. Steroid treatment had no effect upon the increased blood flow 24 h after the endotoxin injection, although from a clinical standpoint the steroid-treated eyes appeared less inflamed. Fluorescein angiography demonstrated a massive increase in iris vessel permeability 6 and 24 h following endotoxin injection. Topical steroid treatment reduced fluorescein entry into the anterior chamber at both time periods. On the other hand, the increase in protein influx into the aqueous humor in the endotoxin-inflamed eye was not inhibited by steroid pretreatment. It is suggested that corticosteroids have a selective effect upon the permeability of different components of the blood-aqueous barrier, namely the ciliary processes and the iris vasculature.

Animals

Effects of silicone oils on corneal endothelial permeability.

Silicone oils, varying by viscosity and manufacturer, were infused into rabbit anterior chambers. Polydimethyl-siloxane oil, 5000 cps, increased corneal endothelial permeability to inulin (mw 5000) and dextran (mw 60000) when measured in vitro at 1, 4 and 7 days after ocular infusion. The effects of five other oils were measured at 7 days after infusion. Four of the oils increased endothelial permeability and induced similar morphological changes. Dow Corning Medical Fluid 360 had no effect on either permeability or morphology of the endothelium. These results show that contact of most silicone oils with corneal endothelium rapidly induces physiological and morphological changes. If these oils, when used as a retinal tamponade, gain access to the cornea they should be removed quickly to avoid the rapid initiation of physiologic changes.

Animals

Toxicity of intracameral thymoxamine.

The anterior chamber of adult pigmented rabbits was perfused with 1 ml of either 0.02% or 0.2% thymoxamine hydrochloride in Balanced Salt Solution. Contralateral eyes were either perfused with BSS alone or remained untouched. Measurements were made of corneal thickness and intraocular pressure prior to perfusion and at days 1, 2, 3 and 7 after perfusion. Observations were made of toxic reactions of ocular tissues using slit-lamp biomicroscopy. No effects were noted with 0.02% thymoxamine but 0.2% caused corneal swelling and a reduction in intraocular pressure at day 1. Neither concentration caused any observable toxic responses. Morphologic studies confirm the absence of effects by 0.02% thymoxamine, and that 0.2% causes disturbance of both corneal endothelium and iris-ciliary processes. This data, together with an earlier report on in vitro studies of thymoxamine, allows the conclusion that 0.02% thymoxamine is a safe concentration for use in the anterior chamber and 0.2% yields adverse reactions.

Animals

Morphologic and physiologic effects of thymoxamine on corneal endothelium and ciliary processes.

Either 0.2 or 0.02% thymoxamine hydrochloride was perfused across the endothelium of isolated rabbit corneas in a specular microscope. Treated corneas did not swell, compared to controls, when perfused with 0.02% thymoxamine, but swelled at 34 microns/hr after 0.2% thymoxamine compared to 10 microns/hr of controls. Morphologically, 0.2% thymoxamine caused many intracellular vacuoles, with far fewer changes after 0.02%. Replacement of the aqueous humor with 0.02% thymoxamine caused no effect on either the corneal endothelium or ciliary process, whereas 0.2% caused small, but significant, changes in both tissues.

Animals

Role of eicosanoids in the ocular response to intracameral hydrogen peroxide.

The intracameral injection of hydrogen peroxide induces a sequence of responses in the tissues bounding the anterior chamber. These changes include intraocular pressure, corneal thickness, iris hyperemia, increased leakiness of the iris vasculature, and edema of the ciliary processes as judged from microscopic examination. Some of these responses appear to include inflammatory effects that may be the result of the local release of eicosanoids. Several antagonists of the arachidonic acid cascade, indomethacin, aspirin, dexamethasone, and nordihydroguaiaretic acid (NDGA) were used to examine their influence on the sequelae of hydrogen peroxide injection. Indomethacin, and high dose (7.5 mg/kg) NDGA were most effective in reducing the number of parameters that were altered after intracameral hydrogen peroxide. Microscopic observations supported the physiological changes and the responses to antagonists. The data indicate that a portion of the ocular tissue responses to intracameral hydrogen peroxide in the rabbit eye may be the result of eicosanoid production in these tissues.

Animals

Effect of PO2 and metabolic inhibitors on ionic fluxes across the isolated rabbit corneal endothelium.

Bicarbonate and sodium fluxes were measured across the isolated rabbit corneal endothelium under the influence of several inhibitors. Depression of PO2 in the bathing medium decreased net sodium movement but increased bicarbonate movement. Furosemide did not alter bicarbonate fluxes at either 10(-4) or 10(-5) M, but increased passive sodium flux leading to a decrease in net flux. Thiocyanate, at 5 x 10(-3) or 5 x 10(-2) M, decreased active bicarbonate flux and hence net flux, but had no effect on sodium fluxes. Dinitrophenol increased only the passive bicarbonate flux while decreasing both active and passive sodium fluxes, albeit unequally, leading to a decreased net flux. Ethacrynic acid affected only passive bicarbonate flux, while decreasing net sodium flux. The stilbene derivatives, SITS and DIDS caused opposite effects on both sodium and bicarbonate fluxes. SITS decreased net bicarbonate flux by decreasing active and increasing passive flux, yet increased net sodium flux. DIDS, however, increased net bicarbonate flux but decreased net sodium flux. The results may be explained by current models for endothelial ion transport that include a Na+/H+ antiport and a HCO3-/Na+ symport system in parallel with an independent pathway for HCO3- exit from the endothelial cells. When compared with prior corneal swelling data using these same inhibitors, the maintenance of corneal thickness appears to be dependent on the variation of ion fluxes from normal values, and the dissociation of the two active ion fluxes. In addition, there appears to be a significant ability of ion transport systems to compensate for disturbances to other ion exchange or transport mechanisms.

Animals

Interaction between progesterone and mifepristone on intraocular pressure in rabbits.

The interaction between a topically administered progesterone, medrysone, and a steroid antagonist, mifepristone, on rabbit intraocular pressure (IOP) has been determined. Medrysone alone increased IOP significantly above parallel controls over the first three weeks; this increase was not sustained. When medrysone and mifepristone were given simultaneously the IOP increased initially, but then fell after two weeks to control levels. When mifepristone was added 14 days after medrysone, the IOP was again reduced to, or below, control levels by mifepristone. The use of mifepristone alone reduced IOP relative to controls and the further addition of medrysone at 14 days had no effect on IOP. It appears that mifepristone is an effective antagonist against progesterone effects on IOP.

Animals

Comparative effects of pilocarpine in different vehicles on pupil diameter in albino rabbits and squirrel monkeys.

Several commercial pilocarpine preparations have been compared for their efficacy of drug delivery as evaluated by changes in pupil diameter, and return to base-line pupil size, in rabbits and squirrel monkeys. Adsorbocarpine, Isoptocarpine, Pilocar, all at 2%, and Pilopine HS gel, 4%, were used. In albino rabbits the order of efficacy, as judged by area under the curve, or maximal pupil diameter change, was Pilopine greater than Isoptocarpine = Adsorbocarpine greater than Pilocar = saline (prepared in this laboratory). In general, greater areas under the curve were associated with greater changes in pupil diameter. Pupil diameter had returned to normal by a maximum of 5 hours after drop instillation. In squirrel monkeys, the maximum pupillary change was statistically (P greater than 0.05) the same for all preparations, as was the percentage change in pupil diameter at 6 hours since pupils were still somewhat constricted at this time after drop instillation. The differences in area under the curve were minor. The greater response in primates compared to rabbits may be due to differences in pigment, intraocular kinetics and a far more active ciliary muscle in primates. Also studied were newly developed, non-surfactant containing, preservative-free polymer- and microparticle-based vehicles. Some of the vehicles, based on cyanoacrylate, modified hyaluronate, anionic copolymers, polyvinyl-pyrrolidone, cross-linked gelatin and microparticles showed greater pupillary changes and areas under the curve in rabbits compared to saline vehicle. When compared to commercial preparations in the monkey eye cyanoacrylate block copolymer and modified hyaluronate showed an increase in efficacy. Polyvinylpyrrolidone, anionic copolymer and cross-linked gelatin were equal to the commercial preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Influence of hydrogen peroxide on adenine uptake by iris, ciliary epithelium and corneal endothelium.

Hydrogen peroxide injected into the anterior chamber of adult rabbits causes a sequence of events that is not seen in young normal rabbits, yet is replicated in young rabbits receiving a catalase inhibitor. The uptake of radiolabeled adenine was measured in corneal endothelial, ciliary epithelial, and iris cells of either normal eyes, eyes injected with hydrogen peroxide or inhibitors of glutathione metabolism. Cellular adenine uptake did not exceed that of the bathing solution, except in corneal endothelia and ciliary epithelium of young animals. Under different experimental conditions intracameral hydrogen peroxide decreased adenine uptake into cells of various tissues compared the same experimental condition where only water injections was made. This occurred even with suppression of catalase activity using 3-aminotriazole. Intravitreal glutathione inhibitors had no effect on adenine uptake. The effects of intracameral hydrogen peroxide seen previously might be explained on the basis of alterations in cellular plasma membrane permeability.

Adenine

Preservative effects on the healing rate of rabbit corneal epithelium.

Benzalkonium chloride (BAK), sodium lauryl sulfate (SLS), chlorhexidine digluconate, thimerosal and polyaminopropyl biguanide were tested for their effects on the rate of corneal epithelial regrowth after mechanical lesions, and BAK and SLS after heptanol-generated lesions in rabbit corneas. Only 1.3% SLS reduced the rate of epithelial healing after three times a day drop application as determined using planar measures of epithelial regrowth. SLS, a common ingredient in soups and shampoos, should be used carefully where a lesion or wound is present in the corneal epithelium.

Animals

Aqueous humor flow rate and intraocular pressure during and after pregnancy.

Intraocular pressure and aqueous humor formation rate have been determined from the first trimester of pregnancy through term, with further determinations 3 months postpartum, in 7 patients. The intraocular pressure showed a consistent, statistically significant fall during pregnancy, returning to values seen in early pregnancy after delivery. Aqueous humor formation rate showed no change during pregnancy. The data indicate that the sustained elevated hormonal levels during pregnancy, either directly or indirectly, cause an increase in fluid outflow conductance from the eye without altering the rate of fluid entry.

Adult

Topical indomethacin and prostaglandins in normal and aphakic rabbit eyes.

Lenses were removed from rabbit eyes using an extracapsular technique. Animals were in three groups; no treatment (NT), post-treatment (PT) and pre- and post-treatment (PPT). Treatment consisted of 2% topical indomethacin given three times a day after surgery, except for the PPT group that received 3 drops on the day prior to surgery and drops at 3 hours and 1 hour before surgery. Prostaglandin levels in ocular tissues and fluids were determined at 7, 14 and 21 days post-surgery. Indomethacin decreased prostaglandin formation in most ocular tissues, and was more effective in the PPT group than in the PT group. The data indicate that topical indomethacin suppresses prostaglandin formation from ocular tissues, and that local prostaglandin release from retina and choroid can provide locally high prostaglandin concentrations, regardless of their source, after lensectomy.

Administration, Topical

Centripetal movement of fluorescein dextrans in the cornea: relevance to arcus.

The centripetal movement of fluorescein and fluorescein-labelled dextrans (4 to 150 kD) from sclera or cut edge of the cornea was determined in isolated rabbit corneas at 4 and 24 h. Corneas were divided into 5.5 mm diameter central core, inner 5.5 to 8 mm donut, 8 to 12 mm peripheral donut and, where applicable, scleral rim. For all molecules greater than sodium fluorescein (376 D) tracer concentrations in the 5.5 mm core and the 5.5 to 8 mm donut were equal. Without sclera rim, the more central portions of the cornea (5.5 mm core and 5.5 to 8 mm donut) had tracer concentrations equal to those of corneas-with-sclera for all tracers greater than 10 kD. The tracer concentrations in the central cornea were the same in the presence or absence of sclera. The data indicate a physiological barrier to the lateral diffusion of molecules greater than 10 kD between the peripheral and more central cornea.

Animals

Sodium and bicarbonate fluxes in regenerating rabbit corneal endothelium.

Rabbit corneal endothelia were subjected to a cryoinjury (-70 degrees C for 15 sec) and sodium and bicarbonate fluxes were determined at various times after induction of the endothelial destruction. A complete monolayer of cells was present by 4 days that consisted of large cells that underwent division over the next 16 days. Unidirectional sodium fluxes were unaltered by the transformation from large to normal sized hexagonal cells. Unidirectional bicarbonate fluxes showed an increase in Jendostr coupled with a decrease in the net Jstrendo flux. As the cells became smaller these bicarbonate fluxes returned to normal values. The data indicate that the cell margin/cell size ratio is not related to the flux rates, thus the paracellular pathway increase with healing is not related to the passage of either sodium or bicarbonate. Secondly, the data indicate separate effects on both sodium and bicarbonate, suggesting that transendothelial movement of the ions can be separated and that they are not necessarily linked in passage across the endothelium.

Animals

Mussel adhesive protein: permeability characteristics when used as a basement membrane.

Mussel Adhesive Protein (MAP) was applied to either denuded rabbit cornea, or dialysis membrane with a 50,000 dalton molecular weight cut-off. The permeability of corneal endothelium or bare stroma was compared with demambranized stroma coated on one surface with MAP. The permeability of dialysis membrane, both in the presence and absence of MAP, was also determined to inulin (5,000 daltons) and dextran (40,000 daltons). Corneal endothelial permeability was much less than that of bare stroma, and coating denuded stroma with MAP on one surface had no effect on stromal permeability. Dialysis membrane permeability was not reduced after coating with different thickness of MAP, indicating that MAP offers little resistance to the passage of even large non-electrolytes and can serve as a basement membrane for cellular or tissue attachment without impairment of nutritional supply to the overlying cells.

Animals

The interrelationship between intraocular pressure and Honan Intraocular Pressure Reducer pressure.

The relationship between the pressure applied to the enucleated human eye using the Honan Intraocular Pressure Reducer (HIPR) and the peak intraocular pressure as a function of initial intraocular pressure has been examined. The peak intraocular pressure is linearly related to the applied HIPR pressure whether the latter is 30, 50, or 75 mm Hg. The slopes relating peak intraocular pressure to initial intraocular pressure at different HIPR settings are parallel. Use of the HIPR at settings greater than 30 mm Hg and an initial IOP of greater than 30 mm Hg could compromise ocular vascular perfusion.

Humans

Distribution of a steroid antagonist in the eye following topical administration.

The distribution of a steroid antagonist, RU486, that is known to reduce rabbit intraocular pressure has been examined in the eye. On an equal tissue weight basis, the corneal epithelium is the site of maximal absorption followed by conjunctival tissues (bulbar and palpebral) and the rest of the cornea. Aqueous humor concentrations of drug vary between 5 X 10(-6) and 5 X 10(-8) at 1 and 24 hours, respectively: these concentrations have been shown by others to inhibit dexamethasone binding to rat thymocytes, and are sufficient to act as an antagonist at steroid receptors in the eye. Multiple drop administration for 10 days (3 drops per day) revealed no accumulation in the treated eye, but did show the presence of drug in the untreated contralateral eye that could explain the contralateral pharmacological effect seen on intraocular pressure after several days of treatment.

Administration, Topical

Effect of ambient pH on corneal endothelial sodium fluxes.

Sodium fluxes across the isolated rabbit corneal endothelium were measured as a function of ambient pH and bicarbonate concentrations. At pH 7, the net sodium flux (J endo str net) was effectively obliterated at all bicarbonate concentrations, relative to controls at pH 7.5. At pH 8, the net sodium flux was obliterated at 5 mM bicarbonate, was unchanged at 25 mM bicarbonate, and was enhanced at 40 mM bicarbonate, relative to controls at pH 7.5. The decrease in net sodium flux under these conditions relative to previously demonstrated maintenance of bicarbonate fluxes under almost identical conditions suggest that sodium and bicarbonate transverse the endothelium by different routes. In addition, changes in unidirectional fluxes, when ambient pH is decreased from 7.5 to 7, are not equal, illustrating that the fluxes probably occur via different pathways. A complex interrelationship exists between sodium, bicarbonate, and proton movement.

Animals