Biomedical subjects

D L Epstein

Publications and source records attributed to D L Epstein.

At least 109 records · Page 6Linked to original sources

PubMed1986

The flow of aqueous humor through micro-porous filters.

Flow resistance was measured as bovine and primate aqueous humor was passed through Nuclepore polycarbonate filters having flow dimensions similar to those found within the juxtacanalicular meshwork of the aqueous outflow network. The results indicate that aqueous humor has a greater flow resistance than isotonic saline; this greater resistance is attributable to proteins or glycoproteins in aqueous humor that obstruct the filters. If the same phenomenon is operative in the aqueous outflow network, it would help to explain discrepancies between calculated and measured aqueous outflow resistance.

Animals↗

PubMed1986

Experimental obstruction to aqueous outflow by pigment particles in living monkeys.

Pigment particles (1 X 10(6)/microliters) isolated from the iris and ciliary body of enucleated cynomolgus monkey eyes were infused into the anterior chamber of seven living cynomolgus monkeys and aqueous humor outflow facility determined by the two-step constant-pressure perfusion technique. Outflow facility acutely decreased 64% in the experimental pigment perfused eyes compared to a 76% increase in the sham-manipulated fellow eyes (P less than 0.001). However, when next measured 1 wk later, facility in the pigment perfused eyes had returned to baseline levels. Repetitive pigment perfusions similarly failed to produce any long-term abnormality in outflow facility. Gonioscopically, a well-defined band of pigment was observed in the trabecular meshwork, which decreased in density with time. Scanning and transmission electron microscopy documented pigment particle phagocytosis by trabecular endothelial cells and macrophages. Forty-two and 105 days after pigment infusion the trabecular meshwork was normal morphologically, and, despite an observed decrease in trabecular pigmentation, morphometry failed to reveal a decrease in trabecular meshwork cellularity in experimental compared to control eyes. These results suggest that factors other than, or in addition to, pigment particle accumulation in the trabecular meshwork must be involved in the mechanism of human pigmentary glaucoma.

Animals↗

PubMed1985

Topical indomethacin therapy before argon laser trabeculoplasty.

Fifty treatment sessions for 43 eyes (35 patients) receiving argon laser trabeculoplasty to one-half the angle were randomly assigned in a double-masked fashion to pretreatment with either topical indomethacin 1% or placebo. In 25 treatments intraocular pressure increased 3 mm Hg or more within four hours. Topical indomethacin pretreatment had no effect on the incidence, magnitude, or time course of this acute increase. It also did not alter the long-term effectiveness of the laser treatment (-3.8 mm Hg in the indomethacin-treated group vs -4.3 mm Hg in the placebo-treated group). The overall incidence of new peripheral anterior synechiae found on gonioscopy at one month was 32% (16 of 50 treatments). Synechiae formation was much higher in blacks (ten of 11 eyes or 91%) than in whites (five of 38 eyes or 13%). Although there was an association between acute anterior chamber inflammation after laser treatment and ultimate synechia formation (P less than .05), indomethacin pretreatment did not alter its occurrence.

Aged↗

PubMed1985

Q-switched neodymium-YAG laser trabeculopuncture in monkeys.

In nine cynomolgus monkeys, trabeculopuncture was performed with a Q-switched neodymium-YAG laser, using a pulse energy of 5 to 7 millijoules and an exposure time of 14 nanoseconds. A penetration into Schlemm's canal was successfully achieved with two to four pulses; this penetration was accompanied by intraocular pressure (IOP) reduction and blood reflux into the anterior chamber. However, after eight days, IOP returned to baseline level, while white tissue was observed gonioscopically to fill in the puncture sites. Histologically, one hour after laser treatment, a blasting effect on the trabecular meshwork was observed with no signs of necrosis. Ater eight days, a hypertrophic scar formed, with the corneal endothelium extending over the scarred surface. At eight weeks and at six months after laser treatment, further shrinkage of the scar and the formation of a membrane over it was evident. Attempts to control scar formation by preventing blood reflux or injecting fluorouracil subconjunctivally for two weeks were unsuccessful. Scar formation at the trabecular puncture site severely limits the applicability of this potentially simple glaucoma treatment.

Animals↗

PubMed1985

Short-term effect of argon laser trabeculoplasty in monkeys.

We performed argon laser trabeculoplasty (ALT) in four cynomolgus monkeys and evaluated the morphologic changes in the trabecular meshwork one hour and 14 hours following the laser treatment. One hour after ALT, disruption of the trabecular beams and coagulative necrosis of the tissue were evident. Fragmented cells and fibrillar tissue debris were found in the trabecular spaces, accumulating in the juxtacanalicular region. This might explain the elevation of intraocular pressure seen immediately following ALT in some glaucomatous patients. Also, many trabecular endothelial cells were rounded up, displaying different stages of leaving the beams; these cells were actively phagocytic. Such stimulation of trabecular meshwork cells with subsequent removal of tissue debris might explain the temporary nature of elevation of intraocular pressure following ALT.

Animals↗

PubMed1985

Neodymium: YAG laser trabeculopuncture in open-angle glaucoma.

Ten eyes of eight patients with open-angle glaucoma (OAG) had neodymium (Nd):YAG trabeculopuncture performed in an investigational protocol as an alternative to surgical intervention. In each, at four to six sites in the mid-trabecular meshwork, three to six superimposed applications were made (2 to 6 mJ). In four of six patients with adult OAG, a small decrease in intraocular pressure (IOP) was noted (from a mean of 25.5 to 20.0 mmHg after 3-4 weeks in the treated eyes, compared to no change at 21 mmHg in the fellow eyes). There appeared to be further attenuation of this IOP effect over the subsequent 2 to 11 months, and all patients demonstrated gonioscopic closure of all the puncture sites with time. One patient demonstrated an acute IOP elevation to 58 mmHg after the procedure, necessitating emergency filtration surgery. In contrast, in four eyes of two patients with juvenile open angle glaucoma, a dramatic lowering of IOP and improvement in tonographic outflow facility was demonstrated, although the effects were only temporary in one patient. YAG laser treatment to the trabecular meshwork may have its greatest potential usefulness when abnormalities in the uveal meshwork are involved, such as in certain cases of juvenile or congenital glaucoma, and may help identify the need for a surgical goniotomy. With more usual forms of OAG, however, widespread use of this technique should be avoided until greater efficacy can be achieved.

Adolescent↗

PubMed1985

Intraocular pressure elevation following Nd:YAG laser posterior capsulotomy.

Intraocular pressures (IOP) and tonographic outflow facilities were measured following neodymium (Nd): YAG laser posterior capsulotomy in 13 pseudophakic and 8 aphakic eyes. Mean intraocular pressure (IOP) peaked by three hours with a mean increase of 13 mmHg, remained elevated by 5 mmHg at 24 hours but returned to baseline by one week. Fourteen eyes (67%) had greater than or equal to 10 mmHg elevation and eight (38%) had greater than or equal to 40 mmHg maximum IOP. All the patients who eventually demonstrated a greater than or equal to 10 mmHg elevation within six hours of the capsulotomy initially had an IOP elevation greater than or equal to 5 mmHg at one hour. The mean outflow facility was reduced from 0.18 microl/min/mmHg before capsulotomy to 0.08 microl/min/mmHg (55%, P less than 0.0001) at four hours and was still decreased at 0.13 microl/min/mmHg (27%, P less than 0.05) at one week. Seventy-five percent of aphakic and 15% of pseudophakic patients had maximum IOP greater than or equal to 40 mmHg (P less than 0.01). Measurements should be performed one hour postlaser in all patients for IOP and three to four hours in aphakic patients, glaucomatous patients, patients receiving greater than or equal to 200 mjoules total laser energy, and patients with greater than or equal to 5 mmHg elevation at one hour in order to detect and treat significant IOP elevations.

Cataract Extraction↗

PubMed1985

Glutathione reductase of calf trabecular meshwork.

Hydrogen peroxide has been found in both calf and human aqueous humor at a level of 25 microM. It is likely, therefore, that trabecular meshwork possesses mechanisms for detoxifying H2O2, both to protect itself and other more distal structures of the outflow pathway from oxidative damage. We have recently demonstrated an active glutathione peroxidase in calf trabecular meshwork. In this study, we have characterized the complementary enzyme, glutathione reductase. The activity was present at a level of 0.120 units/min/g wet of tissue (0.005 units/min/mg soluble protein). The enzyme quickly lost activity in crude extracts but could be stabilized by heating at 60 degrees C for 30 min. Denatured protein was removed by centrifuging at 43,000 X g. Heating at 80 degrees C for 10 min destroyed all enzyme activity. Addition of 1 mM GSSG protected the enzyme completely from heat denaturation; NADP+ and GSH offered some protection but NADPH provided none. The supernatant from the 60 degrees C heat treatment was further purified by affinity chromatography on 2',5'-ADP-agarose. Overall purification was 200-fold with a yield of 80%. The pH optimum of the purified enzyme was 7.0. The KmS for NADPH and GSSG were 19 microM and 78 microM, respectively. The heat inactivation properties of the purified enzyme were identical to those in the crude extract. An enzyme activity stain on disc gel electrophoresis showed that the enzyme exists in only one form.

Animals↗

PubMed1985

Superoxide dismutase and catalase of calf trabecular meshwork.

Superoxide dismutase and catalase activities have been measured in cell-free extracts of calf trabecular meshwork, and for comparison, in calf iris, retina, lens, liver, and erythrocytes. Gel electrophoresis has been used to identify isozymes of each enzyme. The superoxide dismutase and catalase activities per milligram wet weight of calf trabecular meshwork, 0.184 and 0.884 U/mg wet wt, respectively, were comparable to those found in iris and retina, and much higher than those found in lens. Three isozymes of superoxide dismutase were identified in trabecular meshwork. Two of these presumably correspond to cytoplasmic superoxide dismutase, while the third corresponds to a mitochondrial isozyme. A presumably mitochondrial superoxide dismutase activity was also observed in iris and retina, but not in lens. A single catalase isozyme was found in all tissues examined. At physiologic H2O2 concentrations, catalase may have similar levels of activity to glutathione peroxidase. Superoxide dismutase, catalase, and glutathione peroxidase may constitute an important defense mechanism of trabecular meshwork against the toxic O2-. and H2O2 to which it must be continuously exposed from endogenous production as well as from the aqueous humor.

Animals↗

PubMed1984

Neodymium-YAG laser therapy to the anterior hyaloid in aphakic malignant (ciliovitreal block) glaucoma.

In three aphakic eyes and two eyes with intraocular lens implants (five patients, four women and one man, ranging in age from 65 to 76 years) persistent shallow or flat anterior chamber was observed despite multiple patent laser or surgical iridectomies. In each case direct application of the neodymium-YAG laser (3 to 11 mJ) to the anterior hyaloid face resulted in immediate deepening of the anterior chamber. This deepening was sustained in four of the cases. These results confirm previous observations suggesting that the anterior hyaloid can be the locus of abnormality in aphakic malignant (ciliovitreal block) glaucoma. Neodymium-YAG "hyaloidotomy" may be better than penetrating surgery in such cases.

Aged↗

PubMed1984

Experimental iridotomy with the Q-switched neodymium-YAG laser.

Iridotomies were performed on pigmented rabbits with a Q-switched ophthalmic neodymium-YAG (Nd-YAG) laser and an argon laser. Because short-pulsed Nd-YAG lasers are effective in performing capsulotomies of the crystalline lens, injury to the underlying lens was evaluated by slit-lamp biomicroscopy at various intervals following the iridotomy, and then lenses were examined in vitro with the use of procion yellow, an extracellular dye. Patent iridotomies were produced with one to two pulse applications of the Nd-YAG laser. Focal areas of pigment deposition on the lens capsule and focal lens capsule opacities underlying the iridotomy site were observed, but no inadvertent capsulotomies occurred. Lens injury could be minimized through optimal focusing and energy selection. Minimal hemorrhage occurred with Nd-YAG laser iridotomy; prior treatment with the argon laser was not necessary to achieve hemostasis.

Animals↗

PubMed1984

Carbonic anhydrase inhibitors induce elevations in human whole-blood zinc levels.

The use of carbonic anhydrase inhibitors (CAIs) was associated with mean increases in whole-blood zinc levels of 82 micrograms/dL and 70 micrograms/dL, respectively, in a cross-sectional survey and in a prospective study of patients with glaucoma. The time course of the increase suggests that CAIs induce reticulocyte synthesis of carbonic anhydrase.

Carbonic Anhydrase Inhibitors↗

PubMed1984

A one-year multicenter clinical trial of pilocarpine gel.

In a one-year clinical trial of pilocarpine gel, a form designed for once-a-day administration, in 83 patients with glaucoma, average intraocular pressures during gel therapy were equal to or slightly lower than previous values during pilocarpine eyedrop therapy (morning values, 18.7 mm Hg vs 19.7 mm Hg; afternoon values, 20.9 mm Hg vs 20.2 mm Hg). Monitoring of diurnal intraocular pressure showed that 33 of 77 patients (43%) using the gel and 25 of 77 (33%) using eyedrops had afternoon values more than 2 mm Hg higher than their morning values. This difference was not statistically significant. Fifteen of 76 patients (20%) who used the gel for more than eight weeks developed a diffuse superficial corneal haze with gel treatment. The haze persisted 12 months after the gel was discontinued. Although the haze produced no symptoms, its long-term consequences are unknown.

Adult↗

PubMed1984

Treatment of glaucoma.

In the past five years, new therapeutic modalities have been discovered that have revolutionized the medical and surgical management of glaucoma. New methods of drug delivery have been developed for pilocarpine and epinephrine. Timolol maleate has become the most widely used drug in the treatment of glaucoma since it was approved for general use in 1978. This chapter reviews the pharmacology of the newer antiglaucoma medications and gives a perspective on the role of laser surgery in open-angle glaucoma.

Betaxolol↗

PubMed1984

Phosphofructokinase of calf trabecular meshwork.

The activity of phosphofructokinase (PFK), a key regulatory enzyme of glycolysis, has been measured in the 27,000 X g supernatant of homogenates prepared from excised calf trabecular meshwork. The enzyme required NH4+, both at pH 8.5 and pH 7.2. This requirement was not relieved by K+ or AMP. At pH 7.2 and ATP levels of 0.1 to 2.5 mM, PFK was completely inactive in the absence of added AMP or NH4+. PFK was only weakly activated by 0.5 mM AMP or by 5 mM NH4+, but in the presence of both AMP and NH4+, PFK was highly active up to 1 mM ATP. At pH 8.5 and ATP levels of 0.1-12.5 mM, PFK was weakly active in the absence of added NH4+, with or without AMP. With the addition of 5 mM NH4+, PFK was highly active up to 2.5 mM ATP, while AMP was largely without effect. Concentrations of NH4+ as low as 0.03 mM stimulated PFK activity to 20% of maximal, yet the maximum was not reached until NH4+ levels were 10-30 mM. The activation of PFK by AMP and its inhibition by ATP is profoundly modified by pH. In contrast, the requirement for NH4+ is unaffected. This requirement suggests a regulatory role for ammonium ion in controlling the rate of glycolysis in trabecular meshwork. The concentration of ammonium in calf aqueous humor was found to be 0.18 mM, which is in the right range to have an effect.

Animals↗

PubMed1984

Influence of mercurial sulfhydryl agents on aqueous outflow pathways in enucleated eyes.

Enucleated calf and primate eyes were perfused with either p-chloromercuribenzene sulfonate (PCMBS) or p-chloromercuribenzene (PCMB). Both caused a decrease in aqueous outflow that did not result from inhibition of glycolysis in trabecular cells. Morphologic studies of PCMBS-treated primate eyes suggested that the reduction in aqueous outflow occurred as the result of cellular swelling in the trabecular meshwork and, particularly, in the juxtacanalicular connective tissue. These findings suggest that changes in cell volume may influence trabecular outflow resistance and that mercurial-sensitive membrane sulfhydryl groups could participate in the regulation of aqueous outflow.

4-Chloromercuribenzenesulfonate↗

PubMed1984

Hexokinase of calf trabecular meshwork.

Although aqueous outflow is most likely a passive, nonenergy-dependent process, alterations in cellular function in the trabecular meshwork presumably are involved in the development of some types of glaucoma. Accordingly, it seems important to define both the normal and abnormal biochemistry of this tissue. The authors have chosen glycolysis as their starting point, concentrating on the regulatory enzymes, hexokinase, and, in a companion paper, phosphofructokinase. Hexokinase activity has been measured in the 100,000 X g supernatant of homogenates prepared from excised calf trabecular meshwork. Treatment of the homogenate with Triton X-100 before centrifuging caused a twofold increase in measurable activity. Electrophoresis on cellulose acetate revealed types I and II isoenzymes. Electrophoresis on starch gel further resolved type 1 into the adult and fetal subtypes. The principal isoenzyme type released into solution by Triton X-100 was type 1. The kinetic behavior of hexokinase was measured by varying the concentrations of glucose at saturating levels of ATP. Kms calculated from these plots were 7.15 X 10(-2) M, 1.78 X 10(-3) M, and 1.19 X 10(-4) M. Apart from the fetal form of type I hexokinase, the isoenzymes from trabecular meshwork resemble those of other ocular tissues and most extraocular tissues. The special role, if any, of the fetal isoenzyme in regulating glycolysis is not known. Possibly, it is a "kinetically adaptable" isoenzyme.

Animals↗

PubMed1984

Glutathione peroxidase of calf trabecular meshwork.

Glutathione peroxidase was extracted from calf trabecular meshwork. The kinetics of this enzyme were examined, varying the substrates hydrogen peroxide (H2O2), tert- butylhydroperoxide ( tBHP ), and glutathione. The activity of the enzyme in nonpurified homogenates was 596 nmole H2O2 reduced/min/gm wet weight and 680 nmole tBHP reduced/min/gm wet weight (27-28 nmole peroxide reduced/min/mg protein). The apparent Michaelis--Menten constants for H2O2, tBHP , and GSH were 0.012, 0.102, and 2.89 mM, respectively. These data, together with published levels of glutathione in trabecular meshwork, suggest that the trabecular endothelial cell actively detoxifies H2O2.

Animals↗