alpha-chymotrypsin and Glaucoma

Topics: Animals; Chymotrypsin; Disease Models, Animal; Glaucoma; Lasers; Light; Ocular Hypertension; Radiation Injuries, Experimental; Steroids

Topics: Animals; Anterior Chamber; Cataract; Chronic Disease; Chymotrypsin; Ciliary Body; Cortisone; Glaucoma; Humans; Intraocular Pressure; Microscopy, Electron; Rats

Topics: Accommodation, Ocular; Animals; Chlorpromazine; Chymotrypsin; Conjunctiva; Conjunctivitis; Cornea; Drug-Related Side Effects and Adverse Reactions; Eye Diseases; Eyelids; Glaucoma; Humans; Iatrogenic Disease; Lens, Crystalline; Phenothiazines; Refractive Errors

To investigate the therapeutic effect of aqueous humor shunt implants with amniotic membrane transplantation on intractable glaucoma.. Glaucoma was induced in rabbits by the injection of alpha-chymotrypsin into the posterior chamber of the eyes. The rabbits were divided into four groups. Group A: control group, Group B: single shunt tube group, Group C: shunt tube with amniotic membrane transplantation group, Group D: shunt tube with amniotic supporter and amniotic membrane transplantation group. The intraocular pressure(IOP), histology and filterable ability of the tissue around the tubes were studied. The therapeutic effect of the three methods for the glaucoma was compared. From 1998 to 1999, 42 eyes of 41 patients with uncontrolled glacoma after penetrating keratoplasty were randomly assigned into two groups. One group (12 eyes) underwent implantation of shunt tube combining transplantation of amniotic membrane. The other group underwent implantation of a single plate Molteno implant. Clinical records were reviewed to ascertain postoperative IOP, visual acuities, number of medications.. The IOP elevated after the operation and reached at the peak on the third day for all groups and then dropped slowly. The IOP was 33.34 +/- 5.54 mmHg (1 mmHg = 0.133 kPa) for Group A and 27.88 +/- 8.86 mmHg for Group B three months after the operation. There was no statistical difference between the two groups (P = 0.274). The IOP was 22.33 +/- 3.73 mmHg for Group C and there was statistical significant difference between Group C and Group A (P = 0.02) and no difference between Group C and Group B (P = 0.113). The IOP was 15.74 +/- 2.94 mmHg for Group D and there was statistical significant difference between Group D and Group A (P = 0.001) and Group B (P = 0.036). There was no difference between Group D and Group C (P = 0.09). The study of horseradish peroxidase penetrability indicated that there was peroxidase in the tissues around the tube with amniotic membrane transplantation and no peroxidase for simple shunt tube. The fibrous tissue near the tube was denser in simple shunt tube group than that in containing amnion groups. In clinic, the basic data existed no statistical difference between the two groups before surgery. The IOP was 54.42 +/- 9.65 mmHg in shunt tube with amnion group and 43.28 +/- 10.57 mmHg in simple plate Molteno implant group (P = 0.535) before operation. There was significant relativity of the visual acuity before and after the operation in two groups (r = 0.916, P = 0.002 and r = 0.962, P = 0.000). Most patients of the two groups had to use one or two anti glaucoma drugs. The overall success rates were 58.3% for shunt tube with amnion group and 66.7% for Molteno implant group (P = 0.73) within the follow-up period. Kaplan-Meier success analysis indicated one year cumulative success rates of 52.25% for shunt tube with amnion group and of 65.3% for Molteno implant group (P = 0.42).. Amniotic membrane can inhibit proliferation of the scar around the shunt tube. Shunt tube implantation conbining amniotic membrane transplantation can significantly lowered the IOP of glaucoma. Combined using amnion supporter can expend shunt area and significantly reduce IOP of glaucoma. The effect of shunt tube implantation combining amniotic membrane transplantation has the similar result of single plate Molteno implant for the glaucoma after penetrating keratoplasty.

Topics: Adult; Amnion; Animals; Chymotrypsin; Female; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Keratoplasty, Penetrating; Male; Middle Aged; Molteno Implants; Rabbits; Random Allocation; Visual Acuity

Elevated intraocular pressure (IOP) early after cataract extraction with alpha-chymotrypsin is a well-described, common occurrence. To study the incidence of pressure increase and the efficacy of medical therapy, IOP was monitored every 12 hours beginning on the first postoperative day in 68 patients after otherwise uncomplicated intracapsular cataract extraction performed with one milliliter of alpha-chymotrypsin and wound closure with multiple sutures. Patients were randomly assigned to one of three groups: treatment with oral acetazolamide, treatment with topical timolol, or no treatment. Without prophylactic treatment, the prevalence of pressure elevation at 24 hours postoperatively was 69% with IOP greater than or equal to 25 mm Hg; 29% with IOP greater than or equal to 40 mm Hg. This was independent of the type of sutures used (10--0 nylon or 9--0 silk). The patients of four different surgeons had similar rates of occurrence of postoperative glaucoma. Both timolol and acetazolamide were essentially equally effective in lowering IOP in these patients. No adverse side effects were observed. With these effective treatments available if needed, we believe that routine monitoring of the IOP by applanation tonometry during the early postoperative course provides a good opportunity for reducing the risk of complications from excessive intraocular pressure.

Topics: Acetazolamide; Administration, Oral; Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Intraocular Pressure; Ophthalmic Solutions; Postoperative Complications; Propanolamines; Timolol

to compare two models of experimental glaucoma by induction of ocular hypertension in rabbits.. Sixteen New Zealand female rabbits, 2-3 kg were used. Model A (n=6): cauterization of episcleral and perilimbar veins of the right eye (RE) with surgical electrocautery. Model B (n=10): Injection of ?-chymotrypsin in posterior chamber of RE. Intraocular pressure (IOP) was measured before and after the induction of ocular hypertension (OHT), once a week at the same time of day for 40 days, with a manual tonometer. The animals were euthanized by CO2 inhalation. In both models the control was the IOP of the left eye (LE). The mean and standard error (SE) values of IOP, expressed in mmHg, were compared statistically by applying Student's t-test with a significance level of p<0.05.. The IOP in LE (control) of model A: was 12.9±1.05 and in model B: 12.9±1.09. There were no significant differences between the models. Model A: The IOP increase in RE was 14.7% (14.8±1.4) with respect to LE. A significant increase in IOP was observed within the first 24 hours: 23.5±1.9 (p<0.05) compared to the control eye. There were no significant differences with subsequent controls. Model B: The increase in IOP in RE was 129.1% (29.6±3.4) with respect to LE. In all cases an increase was observed from Day 1 (p<0.05). The IOP peak in RE was evidenced on Day 25: 35±3.4 (p<0.05). The increase in IOP induced by model B was significantly higher (p<0.01) than in model A. There was loss of ganglion cells of the retina in both models, but the following anatomo-pathological changes were observed only in model B: buphthalmos, subluxation of the lens and increased excavation of the papilla.. This study indicates that model B is the most appropriate method to induce a rapid, controlled increase of IOP in rabbits and, more importantly, that this increase may be sustained over extended periods of time. This model could be useful for evaluating the efficacy of new ocular drug delivery systems and for further studies of the physiopathology of glaucoma.. comparar dos modelos de glaucoma experimental por inducción de hipertensión ocular en conejos y describir cambios anatomo-patológicos.. Se utilizaron 16 conejos New Zealand, hembras, de 2-3 kg. Modelo A (n=6): cauterización de venas epiesclerales y perilimbares en ojo derecho (OD) con cauterio eléctrico quirúrgico. Modelo B (n=10): inyección intracamerular en OD de ?-quimotripsina. Se midió la presión intraocular (PIO) antes y después de la inducción de la hipertensión ocular (HTO), una vez por semana, a la misma hora del día, durante 40 días, con tonómetro manual. Los animales fueron sacrificados por inhalación de CO2. En ambos modelos la PIO del ojo izquierdo (OI).fue tomado como valor control. La media y error estándar (EE) de los valores de la PIO, expresada en mmHg, fueron evaluadas y comparadas estadísticamente aplicando Test T de Student considerando un nivel de significación de p < 0.05.. La PIO en OI (control) del modelo A: fue 12,9±1,05 y en el modelo B: 12,9±1,09. No se observaron diferencias significativas entre ambas. Modelo A: el aumento de la PIO en OD fue 14,7% (14,8±1,4) con respecto a OI. Se observó un incremento significativo de la PIO dentro de las primeras 24 hs: 23,5±1,9 (p<0,05) comparado con el valor del ojo control. No hubo diferencias significativas con los controles posteriores. Modelo B: el aumento de la PIO en OD fue 129,1% (29,6±3,4) con respecto al OI. En todos los casos se observó un incremento desde el día 1 (p<0,05). El pico de PIO en OD se evidenció el día 25: 35±3,4 (p<0,05). El incremento de la PIO inducida en el modelo B fue significativamente mayor (p<0,01) que en el modelo A. En ambos modelos hubo pérdida de células ganglionares de la retina, pero sólo en el modelo B se observaron los siguientes cambios anatomo-patológicos: buftalmus, subluxación del cristalino y aumento de la excavación de la papila. Conclusión: De acuerdo a este estudio, el modelo B aparece como el método más apropiado a los fines de inducir un incremento rápido y controlado de la IOP en conejos y más importante, este incremento sería capaz de mantenerse alto a lo largo de periodos de tiempos extendidos. Este modelo podría ser de gran utilidad para evaluar la eficacia de nuevos sistemas oculares de liberación de fármacos y realizar futuros estudios de la fisiopatología del glaucoma. De acuerdo a este estudio, el modelo B aparece como el método más apropiado a los fines de inducir un incremento rápido y controlado de la IOP en conejos y más importante, este incremento sería capaz de mantenerse alto a lo largo de periodos de tiempos extendidos. Este modelo podría ser de gran utilidad para evaluar la eficacia de nuevos sistemas oculares de liberación de fármacos y realizar futuros estudios de la fisiopatología del glaucoma

Topics: Animals; Chymotrypsin; Disease Models, Animal; Electrocoagulation; Female; Glaucoma; Intraocular Pressure; Rabbits; Reproducibility of Results; Time Factors; Tonometry, Ocular

To assess the intraoperative and postoperative clinical effects and histologic effects of intracameral administration of α-chymotrypsin in clinically normal dogs undergoing standard intracapsular lens extraction (ICLE).. 6 young adult male dogs without evidence of systemic or ocular disease.. All dogs underwent bilateral ICLE 7 minutes following injection of 75 U of α-chymotrypsin or an identical volume (0.5 mL) of a commercially available balanced saline solution (BSS) into the posterior chamber of the eye. Ease of lens extraction was subjectively assessed and intraoperative intraocular hemorrhage and fibrin accumulation scored. For 27 days after surgery, ocular hyperemia and discharge, chemosis, corneal edema, hyphema, and aqueous flare were scored, and intraocular pressure (IOP) was measured. Thirty days after surgery, histologic evidence of anterior synechia, collapse of and inflammation within the iridocorneal angle, and iritis were scored.. In 5 of 6 dogs, the surgeon was able to correctly identify the eye treated with α-chymotrypsin on the basis of ease of lens extraction. Mean intraoperative intraocular hemorrhage and fibrin scores for BSS-treated eyes were significantly higher than for α-chymotrypsin-treated eyes. Postoperatively, there were no significant differences between treatments for any clinical variables, including IOP Histologic scores were not significantly different between treatments for any variable. Vision was lost as a result of glaucoma in 1 α-chymotrypsin-treated eye and 1 BSS-treated eye.. Intracameral administration of 75 U of α-chymotrypsin 7 minutes before ICLE facilitated lensectomy without apparent adverse effects in clinically normal dogs.

Topics: Animals; Anterior Chamber; Cataract Extraction; Chymotrypsin; Corneal Edema; Dog Diseases; Dogs; Euthanasia; Eye; Eye Diseases; Glaucoma; Hyperemia; Hyphema; Intraocular Pressure; Lens Capsule, Crystalline; Male

The role of nitric oxide (NO) in neuronal degeneration of glaucoma is well established, and drugs to inhibit NO production have been introduced in preclinical studies. The present experiments were made to investigate the pharmacological efficacy of a topical formulation of the nonselective nitric oxide synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME), in an experimental model of glaucoma in rabbits. L-NAME was dissolved in an isotonic, mucoadhesive, viscosized, buffered solution in concentrations of 0.1%, 0.5%, or 1% (w/v). Ocular hypertension (of at least 15 mmHg compared to basal values) was induced by intra-ocular injection of alpha-chymotrypsin. The instillation of L-NAME topical formulations lowered the IOP of hypertensive rabbits in a dose-related manner, with a maximum drop of 12.0 mmHg 60 minutes after administration of the highest concentration. The area under the curve (AUC) of the DeltaIOP (mmHg) versus time (minutes) was 1050.3 +/- 141.7 and 15.1 +/- 2.5 for the 1% L-NAME-treated group and vehicle-treated group, respectively. No change was found in IOP or pupil diameter after instillation of L-NAME eye drops in normotensive rabbits. This study provides the first evidence that topical L-NAME significantly reduces the IOP in a model of ocular hypertension.

Topics: Administration, Topical; Animals; Anterior Chamber; Area Under Curve; Chemistry, Pharmaceutical; Chymotrypsin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Enzyme Inhibitors; Glaucoma; Injections; Intraocular Pressure; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Ophthalmic Solutions; Rabbits; Solvents

We have studied the effects of various angiotensin-converting enzyme (ACE) inhibitors on intraocular pressure (IOP) of rabbits with experimentally induced ocular hypertension and their mechanism of action. Acute ocular hypertension was induced by infusion of 5% glucose (15 ml/kg) through marginal ear vein, whereas chronic glaucoma was induced by injection of alpha-chymotrypsin into the posterior chamber of the eye. IOP was measured by tonometer. All ACE inhibitors were instilled topically in the eye in a sterile solution. The effect of ACE inhibitors also was studied on serum cholinesterase (true and pseudo) and the enzyme ACE in vitro. Enalaprilat, ramiprilat, and fosinopril produced a time-dependent decrease of IOP in both acute and chronic models of ocular hypertension in rabbits. The decrease in IOP was observed for >4 h, and the extent of decrease was comparable to that with both pilocarpine and betaxolol. Prodrugs enalapril and ramipril failed to produced any change in IOP. Losartan also produced a significant decrease in IOP in the chronic model of ocular hypertension in rabbits. All the three ACE inhibitors were found to inhibit ACE activity in aqueous humor. The enzyme cholinesterase was found to be inhibited by enalaprilat, ramiprilat, and fosinopril. However, atropine did not alter the IOP-lowering effect of enalaprilat in rabbits. Indomethacin pretreatment produced slight but significant inhibition of the IOP-lowering effect of enalaprilat in rabbits. Our data suggest that ACE inhibitors enalaprilat, ramiprilat, and fosinopril produce a significant ocular hypotensive effect in acute and chronic models of ocular hypertension in rabbits. Inhibition of ACE in aqueous humor, and in ocular tissues, resulting in reduced angiotensin II formation, could be one of the major mechanisms responsible for the IOP reduction by ACE inhibitors in rabbits.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Animals; Aqueous Humor; Cholinesterases; Chronic Disease; Chymotrypsin; Glaucoma; Intraocular Pressure; Ocular Hypertension; Peptidyl-Dipeptidase A; Rabbits

Important physiological and physio-pathological functions are played by several carbonic anhydrase (CA, EC 4.2.1.1) isozymes, which are strongly inhibited by aromatic and heterocyclic sulfonamides. Here we report several new types of such sulfonamides, incorporating furan-, thiophene- and pyrrole-carboxamide moieties in their molecules. Some of these compounds showed very good CA II and CA IV inhibitory properties. with affinities for the enzymes in the low nanomolar range. Due to their relatively low water solubility, some of the most active CA II inhibitors reported here have been formulated as aqueous suspension for topical administration as antiglaucoma agents. in normotensive and glaucomatous rabbits. The derivatives incorporating furan- and pyrrole-carboxamide moieties (but not the corresponding thiophene-substituted derivatives), showed effective and long-lasting intraocular pressure (IOP) lowering both in normotensive as well as glaucomatous animals, with potencies superior to dorzolamide and brinzolamide, the two available topically acting sulfonamide drugs. This is the first example of non-water soluble sulfonamides that significantly lower IOP, being thus similar with the recently introduced drug brinzolamide, which belongs to a completely different chemical family of antiglaucoma sulfonamides.

Topics: Animals; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Chymotrypsin; Cornea; Glaucoma; Humans; Isoenzymes; Male; Molecular Structure; Ocular Hypertension; Rabbits; Sulfonamides

Increased intraperitoneal pressure in the head-down position is associated with a significant increase in intraocular pressure (IOP) in rabbits with alpha-chymotrypsin-induced glaucoma. Also, the retinal cells are weakened by the induction of increased IOP, and/or glaucoma, even when IOP is controlled by adequate therapy; therefore, these cells need to be protected from any additional aggression. Actin and vimentin are proteins of the retinal cell cytoskeleton that react readily in response to retinal injuries, including ischemia and glaucoma. Early changes in these cytoskeleton proteins determine the morphological changes observed after retinal damage. Therefore, we set out to investigate intracytoplasmic changes in vimentin and actin after a 4-h CO(2) pneumoperitoneum in the head-down position in rabbits with alpha-chymotrypsin-induced glaucoma.. Twenty-one rabbits with alpha-chymotrypsin-induced glaucoma in one eye received general anesthesia for 4 h in the head-down position and were randomly allocated to have (a) no pneumoperitoneum, (b) a 10 mmHg CO(2) pneumoperitoneum, or (c) a 20 mmHg CO(2) pneumoperitoneum. At the end of the trial, both the right glaucomatous and the left control eyes were enucleated and investigated immunocytochemically for alterations in vimentin and actin, and morphologically for retinal layer disorganization.. Except for the preexisting morphological changes induced by glaucoma, both the control and the glaucomatous eyes in all rabbits appeared normal in terms of retinal layer organization and the distribution of intracellular vimentin and actin whatever the intraperitoneal pressure level applied.. In rabbits with alpha-chymotrypsin-induced glaucoma, a 4-h CO(2) pneumoperitoneum of

Topics: Actins; Analysis of Variance; Animals; Biomarkers; Carbon Dioxide; Chymotrypsin; Glaucoma; Head-Down Tilt; Immunohistochemistry; Intraocular Pressure; Ischemia; Pneumoperitoneum, Artificial; Rabbits; Random Allocation; Retina; Retinal Vessels; Time Factors; Vimentin

Increased intraperitoneal pressure is associated with physiological changes including alterations of intraocular pressure (IOP). We have previously shown that IOP is not adversely affected by increased intraperitoneal pressure up to 15 mm Hg in women with no preexisting eye disease. The aim of this study was to measure IOP changes associated with increased intraperitoneal pressure (up to 15 mm Hg) of 2 h duration in 12 rabbits with alpha-chymotrypsin-induced glaucoma. A reliable model of glaucoma was created by injecting alpha-chymotrypsin into the posterior chamber of the right eye in 12 rabbits. Thereafter, 5 of the 12 rabbits with glaucomatous eyes were treated with topical timolol. The left eye was used as a control. During pentobarbital general anesthesia, increased intraperitoneal pressure up to 15 mm Hg was created by intraperitoneal CO2 insufflation. Body temperature and expired CO2 were kept constant throughout the study. IOP measurements were made using an electronic pneumotonometer. IOP, mean arterial pressure, heart rate, and central venous pressure were recorded in head-up and head-down positions before, during, and after increased intraperitoneal pressure. The IOP of both eyes, in both treated and untreated rabbits, increased significantly from baseline only when increased intraperitoneal pressure associated with the head-down position resulted in a significant increase in central venous pressure. However, the IOP increase remained within the diurnal range. The major finding of this study is that, in a reliable model of glaucoma, CO2 pneumoperitoneum was associated with an increase in IOP when a head-down position was combined with pneumoperitoneum.. In rabbits with alpha-chymotrypsin-induced glaucoma, increased intraperitoneal pressure (up to 15 mm Hg) resulted in a significant intraocular pressure increase when pneumoperitoneum was associated with the head-down position. However, the intraocular pressure increase remained within the diurnal range.

Topics: Adjuvants, Anesthesia; Administration, Topical; Anesthesia, General; Animals; Antihypertensive Agents; Blood Pressure; Body Temperature; Carbon Dioxide; Central Venous Pressure; Chymotrypsin; Disease Models, Animal; Glaucoma; Head-Down Tilt; Heart Rate; Insufflation; Intraocular Pressure; Male; Ocular Hypertension; Pentobarbital; Pneumoperitoneum, Artificial; Posture; Pressure; Rabbits; Reproducibility of Results; Time Factors; Timolol; Tonometry, Ocular

Arylpiperazine derivatives were synthesized and investigated in this study. Two animal models, including an intraocular pressure (IOP) recovery method and an alpha-chymotrypsin-induced glaucoma model, were used to determine the ocular pharmacological effects of the arylpiperazine derivatives. In the IOP recovery method, New Zealand rabbits with normal IOP were instilled with 50 microliters of 0.5% eye drops, then 10% sodium chloride solution was infused through the ear marginal vein. The relative percent of IOPs were calculated, then delta IOPt% was obtained from the difference of IOPt% between the treated and controlled eye. In the alpha-chymotrypsin-induced glaucoma model, the induced glaucoma rabbits were topically instilled with 0.5% arylpiperazines onto the eyes, and then the IOP changes were calculated to evaluate the effect of eye drops. Our results showed that in the IOP recovery method, BG31 and YCT2-2 demonstrated a very significant effect for reducing IOP; delta IOPt% were -27.6 and -25.5 for BG31 and YCT2-2, respectively. Two other compounds, C219 and C220 also lowered IOP, but the effects were less significant. In alpha-chymotrypsin-induced glaucoma, the maximum effect of YCT2-2 on the IOP was found at 5 hrs. The delta IOP and delta delta IOP were -12.5 +/- 1.7 and -5.8 +/- 1.1 mmHg (p < 0.01), respectively. For BG-31 and C220, there existed a trend to increase IOP with time. In the study, we found that YCT2-2 with higher solubility in the acidic condition was correlated to the significant IOP lowering effect.

Topics: Administration, Topical; Animals; Chymotrypsin; Disease Models, Animal; Female; Glaucoma; Intraocular Pressure; Male; Ophthalmic Solutions; Piperazines; Rabbits; Tonometry, Ocular

The aim of this study was to set-up and validate the use of a radio-telemetry system in order to record IOP in chronic ocular hypertensive animals. The transmitter of a miniaturized radio-telemetry system was implanted in rabbits, and its catheter was tunnelled subcutaneously to the superior conjunctival sac and inserted into the midvitreous. Implantation was performed in chronic ocular hypertensive rabbits induced by an injection of alpha-chymotrypsin into the posterior chamber of the eye. The effects of 0.5% timolol maleate, 2% dorzolamide hydrochloride and 1% epinephrine were assessed and compared after topical administration in this model. Implanted radio-telemetric system into the vitreous allowed IOP measurement for more than 6 months. In this study, circadian IOP kinetic profiles were monitored in all animals over 24 h for 3 weeks. Timolol maleate was found significantly potent in reducing IOP, while changes depended on the nyctemeral period. Dorzolamide hydrochloride induced a very large IOP reduction and was found to be also well effective at night. We evidenced a biphasic time-dependent effect after topical epinephrine, with a long lasting IOP increase occurring after the administration. This change was found to be related to side effects resulting from a poor ocular tolerance of this drug in the rabbit, leading to either a complete eye closure or a higher blinking rate. By using our method, we confirmed the pressure pulses and undershoots occurring during blinking. Radio-telemetry in chronic glaucoma rabbits appears as a refined method to assess anti-glaucoma drug activity, 24 hours a day, for long-term periods in unrestrained animals, while also providing information on the ocular side effects of eye drops.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Carbonic Anhydrase Inhibitors; Chymotrypsin; Circadian Rhythm; Disease Models, Animal; Epinephrine; Female; Glaucoma; Intraocular Pressure; Ophthalmic Solutions; Rabbits; Sulfonamides; Telemetry; Thiophenes; Timolol

ANF binding sites were analysed in the ciliary processes of rabbits with unilateral experimental glaucoma which had been induced by injecting alpha-chymotrypsin into the posterior chamber of the right eyes. The intraocular pressure (IOP) of glaucomatous eyes was significantly greater (28.4 +/- 4 mmHg) than that of normotensive control eyes (13.1 +/- 1.4 mmHg, mean +/- S.E.M., n = 23, P less than 0.05). ANF concentrations in aqueous humour and the ciliary processes were significantly higher in glaucomatous eyes (91 +/- 2 pg ml-1 and 30.4 +/- 4.2 pg g-1 wet weight) than in normal eyes (3.1 +/- 2.2 pg ml-1 and 10.2 +/- 2.7 pg g-1 wet weight, respectively, n = 6, P less than 0.01). The number of ANF-binding sites (Bmax) in the ciliary processes of glaucomatous rabbit eyes was significantly decreased in comparison to the controls (24 +/- 4 vs. 13 +/- 3 fmol mg-1 protein, n = 10, P less than 0.05). These data suggest that ANF receptors in the ciliary processes are down-regulated and that ANF may play an important role in the pathophysiology of experimental glaucoma.

Topics: Animals; Aqueous Humor; Atrial Natriuretic Factor; Binding Sites; Chymotrypsin; Ciliary Body; Glaucoma; Intraocular Pressure; Rabbits; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

A newly synthesized topical carbonic anhydrase inhibitor, 6-hydroxyethoxy-2-benzothiazole sulfonamide (6-HS), was administered systemically and topically to alpha-chymotrypsin-induced glaucoma rabbits to evaluate its ocular hypotensive effect. A significant IOP lowering effect was observed after topical application of 50 microL of 3% 6-HS gel, but a dose of 50 microL of 3% 6-HS suspension failed to reduce IOP. The maximal magnitude of reduced IOP after topical gel instillation was 24.4%, very close to the result obtained following intravenous injection of 6 mg/kg of 6-HS (23.3%). However, the blood levels of 6-HS after topical instillation with 3% 6-HS gel was much lower than that following 6 mg/kg of 6-HS injected intravenously (less than 5%). Since a lower dose of 6-HS (1 mg/Kg) administered intravenously did not cause a significant drop in IOP, it is reasonable to deduct that the ocular hypotensive effect of 6-HS applied topically can then be attributed to the inhibition of intraocular carbonic anhydrase activity. It was also noted that a larger dose of intravenous administration of 6-HS (20 mg/Kg) had a more profound IOP and blood pressure reducing effect with moderate metabolic acidosis.

Topics: Animals; Benzothiazoles; Carbonic Anhydrase Inhibitors; Chymotrypsin; Disease Models, Animal; Ethoxzolamide; Female; Glaucoma; Intraocular Pressure; Male; Rabbits

A newly synthesized topical carbonic anhydrase inhibitor, 6-hydroxyethoxy-2-benzothiazole sulfonamide (6-HS), was used as a model drug to determine its corneal and scleral permeabilities in rabbit eyes. The corneal permeability coefficient of 6-HS for short duration glaucoma and normal rabbit eye was not significantly different (its mean value was around 2.9 x 10(-6) cm/sec), while the corneal permeability coefficient for long duration glaucoma rabbit eye was 1.8 times greater than that for the normal eye. The sclera was found to have a higher permeability than the cornea in that after four hours perfusion the amount of drug which passed through the sclera was 11 times greater than that of the cornea. In addition, it was also noted that after topical instillation of 50 microL of 3% 6-HS gel the aqueous humor concentrations of 6-HS in short duration glaucoma eye and normal eye were not statistically different.

Topics: Administration, Topical; Animals; Aqueous Humor; Benzothiazoles; Carbonic Anhydrase Inhibitors; Chymotrypsin; Cornea; Ethoxzolamide; Female; Gels; Glaucoma; Male; Permeability; Rabbits; Sclera; Time Factors

Atrial natriuretic factor (ANF) concentration in the aqueous humor (AH) was studied in rabbits with experimental glaucoma induced by injecting alpha-chymotrypsin into the posterior chamber. In normal rabbit eyes, the ANF concentration in AH was 3.1 +/- 1.2 pg/ml (mean +/- SEM; n = 12), ranging from 0 to 5.8 pg/ml, whereas it was significantly higher in AH from glaucomatous rabbit eyes, being 81.0 +/- 9.8 pg/ml (n = 12). These findings were correlated with intraocular pressure (IOP), which was 13.0 +/- 2.4 mmHg (n = 12) in normal rabbit eyes and significantly greater in glaucomatous eyes: 24.4 +/- 3.0 mmHg (n = 12). Our data indicate that enhanced ANF release in AH during experimental glaucoma may play an important physiological role in modulating IOP.

Topics: Animals; Aqueous Humor; Atrial Natriuretic Factor; Chymotrypsin; Eye; Glaucoma; Male; Rabbits

Topics: Animals; Chymotrypsin; Colforsin; Glaucoma; Intraocular Pressure; Rabbits

Various studies were conducted to evaluate the effects of timolol, an S-enantiomer, relative to its R-enantiomer upon intraocular pressure and related ocular systems in the rabbit. The R-enantiomer was about one-third as potent as timolol in displacing 3H-dihydroalprenolol binding to iris-ciliary body tissue, reducing aqueous humor formation, and lowering intraocular pressure of alpha-chymotrypsin hypertensive eyes. In contrast, the R-enantiomer was 50 to 90 times less potent than timolol in antagonizing the effects of isoproterenol on pulmonary and atrial beta-adrenergic receptors. The data indicate that the R-enantiomer may lower intraocular pressure in man at concentrations less likely than timolol to block extraocular beta-adrenergic receptors. Finally, to account for the differential effect of the R-enantiomer upon ocular as opposed to extraocular beta-adrenergic receptors, it is tentatively suggested that this agent may also act upon a population of ocular beta-adrenergic receptors showing relatively poor stereoselectively.

Topics: Animals; Aqueous Humor; Binding Sites; Bronchi; Chymotrypsin; Ciliary Body; Dihydroalprenolol; Dose-Response Relationship, Drug; Female; Glaucoma; Guinea Pigs; Humans; Intraocular Pressure; Iris; Male; Ocular Hypertension; Rabbits; Receptors, Adrenergic, beta; Time Factors; Timolol; Trachea

An analogue of ethoxzolamide, 6-hydroxyethoxzolamide, was synthesized to enhance corneal permeability yet retain carbonic anhydrase inhibitory activity for use in lowering intraocular pressure. In a 1% suspension, the analogue caused a small but statistically significant unilateral reduction of IOP when applied to one eye of normal rabbits. When formulated in a gel vehicle, 6-hydroxyethoxzolamide caused a more prolonged and larger reduction in IOP in normal and ocular hypertensive rabbits compared with its effect in suspension or with the parent compound.

Topics: Animals; Benzothiazoles; Carbonic Anhydrase Inhibitors; Chymotrypsin; Ethoxzolamide; Gels; Glaucoma; Intraocular Pressure; Ophthalmic Solutions; Rabbits; Suspensions; Thiazoles

The antiglaucomatous effects of Glauplex 2 and pilocarpine nitrate on alpha-chymotrypsine-induced experimental glaucoma were studied in 8 rabbits. Changes in intraocular pressure were measured over a period of 12 hours after a single instillation of Glauplex 2 or two instillations of 2.6 p. cent pilocarpine nitrate at t = 0 and t = 6 hours. The antihypertensive effect of a single instillation of Glauplex 2 was shown to be approximately equivalent to that of two instillations of 2.6 p. cent pilocarpine nitrate.

Topics: Animals; Chymotrypsin; Delayed-Action Preparations; Disease Models, Animal; Glaucoma; Ophthalmic Solutions; Pilocarpine; Rabbits; Tonometry, Ocular

A non-existent or extremely flat anterior chamber following cataract extraction is now very rare due to the fact that waterproof wound closure has become standard practice. Among 1,051 cataract operations carried out in our clinic during the past three years this complication was observed only 13 times, i.e. in 1,2 percent of the cases. The complication occurred slightly more frequently in diabetics and patients with glaucoma. Methods of preventing the complication and both drug and surgical treatment are discussed. In our cases surgical intervention was never necessary.

Topics: Anterior Chamber; Cataract Extraction; Chymotrypsin; Diabetes Complications; Glaucoma; Humans; Surgical Wound Dehiscence

After intracapsular lens extraction with alpha-chymotrypsin three groups of 14 patients were formed. The first group was given Timolol 0.25% 2 x 1 drops, the second acetazolamide in sustained release form 1 x 500 mg and the third served as control. In all three groups the postoperatively elevated pressure diminished significantly in the first five postoperative days. The pressure diminution on the fourth and fifth postoperative day was accelerated by Timolol but not by acetazolamide.

Topics: Acetazolamide; Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Postoperative Complications; Propanolamines; Timolol

The injection of alpha-chymotrypsin into the posterior chamber of the eye is known to produce an experimental ocular hypertension of long duration in animals. The present study reports the pathological changes which occur in the eye during the first nine months after the ocular injection of alpha-chymotrypsin in rabbits. Six weeks after treatment most of the eyes showed a buphthalmia and an intraocular pressure elevation which varied greatly from animal to animal. The anterior chamber angle of the treated eyes showed a progressive enlargement. Several days after the enzyme injection a transient increase in thickness of the cornea and Descemet membrane was noted. Cupping of the optic disc, characterized by a total disappearance of the optic nerve head fibers and an excavation beginning at margins of the retina appeared after four months and in most cases were present seven months after the treatment. More or less prominent retinal degeneration was also evidenced three months after enzyme injection. The results indicate alpha-chymotrypsin-induced occular hypertension in the rabbit leads after several months to pathological change in the eye analogous to that observed in human glaucoma.

Topics: Animals; Anterior Chamber; Chymotrypsin; Cornea; Descemet Membrane; Disease Models, Animal; Eye; Glaucoma; Intraocular Pressure; Male; Optic Disk; Rabbits; Retina; Tonometry, Ocular

The authors have carried out a statistical study on two large groups of patients operated on for cataract and in whom the enzyme alph-chymotrypsin has been used, and the occurrence of ocular hypertension has been examined. One group, which contained 1,003 operations most of which were under the microscope using a firm closure technique, was compared with another group of 324 cases operated under the same conditions but without using the enzyme. In all cases the intraocular pressure was measured 24-48 hours after the operation. The rise in pressure, the rapidity of its development were studied together with its duration and the concentration of the enzyme. In addition these findings were compared with another group of 2,334 eyes operated on several years previously with standard techniques using a less hermetic wound suture, without a microscope, with alpha-chymotrypsin, but whose tensions were controlled from the third week. The results show conclusively that there is a greater frequency of the occurrence of raised intra-ocular pressure when the enzyme is used (40,3%) than when it is not used (25,3%). This ocular hypertension persists in all cases to the end of three weeks. The time of the appearance of the hypertension, the numbers affected and the duration of the intraocular pressure were not significantly meaningful in the statistical analysis.

Topics: Cataract Extraction; Chymotrypsin; Drug Evaluation; Glaucoma; Humans

Increased intraocular pressure in the immediate postoperative period commonly occurs after cataract extraction. We compared a series of patients operated on through a limbal section to a series operated on through a corneal section. The incidence of increased IOP was significantly lower in the corneal section group. This supports the theory that trabecular damage is a major factor in causing early increased IOP after cataract extraction.

Topics: Cataract Extraction; Chymotrypsin; Conjunctiva; Cornea; Glaucoma; Humans; Intraocular Pressure; Postoperative Complications; Trabecular Meshwork

Topics: Animals; Cats; Cattle; Chickens; Chymotrypsin; Disease Models, Animal; Dogs; Glaucoma; Haplorhini; Humans; Hydrophthalmos; Light; Primates; Rabbits; Rats; Swine

D-isoproterenol d-bitartrate applied topically lowers intraocular pressure (IOP) in normal albino rabbits and rabbits with alpha-chymotrypsin-induced glaucoma. This effect is independent of any effect on systemic blood pressure or pulse rate. A similar response could not be obtained in monkey or human eyes. Subconjunctival injection of d-isoproterenol d-bitartrate to monkey eyes did not alter IOP.

Topics: Administration, Topical; Animals; Chymotrypsin; Glaucoma; Haplorhini; Humans; Intraocular Pressure; Isoproterenol; Pulse; Rabbits; Tachycardia

Topics: Adult; Aged; Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Middle Aged

The postoperative course of 141 eyes in 115 patients undergoing uncomplicated intracapsular cataract extraction was reviewed. Alpha-chymotrypsin as used in our institution did not increase the percentage of eyes developing significant postoperative ocular hypertension. Smaller amounts of enzyme and a shorter waiting period than have heretofore been advocated are adequate for clinically effective zonulysis and appear to be protective against "enzyme glaucoma." Indeed, we found that among non-diabetics, those receiving enzyme experienced a lower incidence of postoperative ocular hypertension than did those not receiving enzyme. The one factor in our series related to an increased percentage of postoperative hypertensive responses was diabetes mellitus.

Topics: Adult; Age Factors; Aged; Cataract Extraction; Chymotrypsin; Diabetes Complications; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged

Experimental glaucoma was produced in 50% of rabbit eyes by injecting 75 units of alphachymotrypsin into the posterior chamber. The elevation of intraocular pressure was stable, rarely exceeded 50 mm Hg, and lasted one year or longer. Progressive buphthalmos first appeared 2 to 3 weeks following injection of the enzyme. Ocular histologic changes included bullous keratopathy, iris and ciliary body atrophy, and cupping of the optic disc. The optic nerve became atrophic but no cavernous degeneration occurred. In the retina there was thinning of the nerve fiber layer and loss of ganglion cells with preservation of the other retinal elements. The mechanism leading to glaucoma following alphachymotrypsin injection is unclear. This study demonstrated formation of peripheral anterior synechiae and reduction of outflow facility within 2 weeks following injection and these factors may play a role.

Topics: Animals; Chymotrypsin; Cornea; Descemet Membrane; Fundus Oculi; Glaucoma; Hydrophthalmos; Intraocular Pressure; Optic Atrophy; Optic Nerve; Rabbits; Retina

Topics: Adult; Age Factors; Aged; Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Middle Aged

Topics: Aged; Aqueous Humor; Cataract Extraction; Chymotrypsin; Cornea; Edema; Eye Movements; Glaucoma; Humans; Intraocular Pressure; Lenses; Middle Aged; Pain, Postoperative; Prostheses and Implants; Time Factors; Tonometry, Ocular

Topics: Animals; Aqueous Humor; Biological Transport; Blood; Chymotrypsin; Drug Antagonism; Glaucoma; Indomethacin; Injections; Intraocular Pressure; Male; Premedication; Rabbits; Time Factors; Tonometry, Ocular

Topics: Animals; Anterior Chamber; Cataract; Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Keratitis; Rabbits; Retinal Diseases

Topics: Acetazolamide; Aged; Cataract; Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Intraocular Pressure; Mannitol; Middle Aged; Postoperative Complications; Time Factors; Tonometry, Ocular

Topics: Aldehydes; Animals; Anterior Chamber; Basement Membrane; Chymotrypsin; Ciliary Body; Collagen; Connective Tissue Cells; Cornea; Epithelial Cells; Eye; Glaucoma; Glutarates; Haplorhini; Intraocular Pressure; Macaca; Macrophages; Manometry; Microscopy, Electron; Optic Nerve; Perfusion; Pinocytosis; Rats; Sclera; Tonometry, Ocular

Topics: Animals; Cataract Extraction; Chymotrypsin; Cornea; Glaucoma; Intraocular Pressure; Rabbits; Wound Healing

Topics: Cadaver; Cataract Extraction; Chymotrypsin; Ciliary Body; Glaucoma; Humans; In Vitro Techniques; Intraocular Pressure; Lens, Crystalline; Microscopy, Electron, Scanning; Ophthalmic Solutions; Perfusion; Time Factors

Topics: Anterior Chamber; Chymotrypsin; Ciliary Body; Cornea; Diabetes Complications; Eye Diseases; Eye Injuries; Eye Neoplasms; Glaucoma; Humans; Intraocular Pressure; Iris; Lens, Crystalline; Microscopy, Electron, Scanning; Ophthalmologic Surgical Procedures; Optic Nerve; Sclera; Uvea

Topics: Adult; Aged; Animals; Anterior Chamber; Chymotrypsin; Cornea; Drainage; Eye; Female; Follow-Up Studies; Foreign-Body Reaction; Glaucoma; Gold; Hemorrhage; Humans; Injections; Intraocular Pressure; Iris; Male; Middle Aged; Postoperative Complications; Rabbits; Sclera; Tonometry, Ocular

Topics: Cataract; Cataract Extraction; Chymotrypsin; Conjunctiva; Glaucoma; Humans; Intraocular Pressure; Methods; Postoperative Complications; Suture Techniques; Sutures

Topics: Animals; Chymotrypsin; Ciliary Body; Glaucoma; Haplorhini; Intraocular Pressure

Topics: Animals; Cataract Extraction; Chymotrypsin; Ciliary Body; Erythrocytes; Glaucoma; Haplorhini; Injections; Leukocytes; Microscopy, Electron; Microscopy, Electron, Scanning

Topics: Cataract Extraction; Chymotrypsin; Diabetes Mellitus; Eye Injuries; Glaucoma; Humans; Intraocular Pressure; Methods; Middle Aged; Rupture; Visual Acuity

Topics: Animals; Anterior Chamber; Aqueous Humor; Chymotrypsin; Glaucoma; Intraocular Pressure; Rabbits

Topics: Animals; Chymotrypsin; Glaucoma; Intraocular Pressure; Rabbits

Topics: Anesthesia, Spinal; Anti-Bacterial Agents; Antineoplastic Agents; Antiviral Agents; Argyria; Blindness; Chymotrypsin; Conjunctivitis; Cortisone; Drug Eruptions; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Epinephrine; Eye Diseases; Glaucoma; Humans; Intraocular Pressure; Lacrimal Duct Obstruction; Miotics; Mydriatics; Ophthalmic Solutions; Optic Neuritis; Retinal Detachment; Vasoconstrictor Agents

Topics: Acetazolamide; Adolescent; Adult; Aged; Cataract Extraction; Chymotrypsin; Corneal Injuries; Corneal Transplantation; Dexamethasone; Electronics, Medical; Eye Burns; Glaucoma; Humans; Intraocular Pressure; Iritis; Keratoconus; Middle Aged; Pilocarpine; Postoperative Complications; Pupil; Tonometry, Ocular

Topics: Animals; Anterior Chamber; Chymotrypsin; Ciliary Body; Cornea; Glaucoma; Haplorhini; Injections; Intraocular Pressure; Iris; Lens, Crystalline; Microscopy, Electron; Optic Atrophy; Optic Nerve; Retina

Topics: Aged; Cataract Extraction; Chloramphenicol; Choroid; Chymotrypsin; Eye Diseases; Female; Glaucoma; Humans; Male; Middle Aged; Postoperative Complications

Topics: Acetazolamide; Cataract Extraction; Chymotrypsin; Female; Glaucoma; Humans; Intraocular Pressure; Male; Methylprednisolone; Pilocarpine; Scopolamine

Topics: Black or African American; Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Intraocular Pressure

Topics: Aged; Anterior Chamber; Aqueous Humor; Cataract Extraction; Chymotrypsin; Corneal Dystrophies, Hereditary; Eye Diseases; Female; Glaucoma; Humans; Hyphema; Iris; Keratitis; Penicillin G; Postoperative Complications; Retinal Detachment; Therapeutic Irrigation

Topics: Aged; Cataract Extraction; Chymotrypsin; Female; Glaucoma; Humans; Intraocular Pressure; Male; Time Factors; Trypsin

Topics: Animals; Chymotrypsin; Electroretinography; Glaucoma; Haplorhini; In Vitro Techniques; Intraocular Pressure; Optic Nerve; Photomicrography

Topics: Adolescent; Adult; Aged; Cataract; Cataract Extraction; Child; Chymotrypsin; Corneal Dystrophies, Hereditary; Corneal Opacity; Cryosurgery; Glaucoma; Humans; Middle Aged; Myopia; Surgical Instruments; Uveitis

Topics: Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Intraocular Pressure

Topics: Acetazolamide; Cataract Extraction; Chymotrypsin; Geriatrics; Glaucoma; Humans; Manometry; Postoperative Care; Postoperative Complications

Topics: Aqueous Humor; Cataract Extraction; Chymotrypsin; Glaucoma; Gonioscopy; Manometry; Pharmacology; Tonometry, Ocular; Toxicology

Topics: Atropine; Cataract Extraction; Chymotrypsin; Geriatrics; Glaucoma; Humans; Lidocaine; Ophthalmology; Postoperative Care; Retinal Detachment; Toxicology

Topics: Cataract; Cataract Extraction; Chymotrypsin; Corneal Dystrophies, Hereditary; Corneal Transplantation; Fuchs' Endothelial Dystrophy; Geriatrics; Glaucoma; Humans; Postoperative Complications

Topics: Cataract Extraction; Chymotrypsin; Geriatrics; Glaucoma; Manometry; Middle Aged; Statistics as Topic; Toxicology

Topics: Biometry; Cataract Extraction; Chymotrypsin; Geriatrics; Glaucoma; Statistics as Topic

Topics: Cataract Extraction; Chymotrypsin; Glaucoma; Gonioscopy; Humans; Manometry; Postoperative Complications; Statistics as Topic; Toxicology

Topics: Cataract Extraction; Chymotrypsin; Glaucoma; Humans; Postoperative Complications