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PubMed2002

Laser-grid trabeculectomy in rabbits: an experimental in-vivo study.

BACKGROUND: Laser-grid trabeculectomy (TE) is a modification of micro-TE designed to enhance the intra- and postoperative safety of filtering surgery by creating several small oval fistulas (max. diameter <200 microm) beneath a scleral flap without peripheral iridectomy. METHODS: After dissecting the conjunctiva and a conventional scleral flap, 10 small perforating fistulas were created in five pigmented rabbits in the region of the gray-white border using an erbium:YAG laser with a beveled side-firing 200 microm endoprobe; conventional TE with iridectomy was performed in another five animals. Anterior chamber inspection and IOP measurements of both eyes were conducted on days 1, 4, and 14 after operation. After the last inspection eyes were saved for morphological analysis. RESULTS: Both procedures (laser-grid and conventional TE) led to a reduction of intraocular pressure in the treated eye compared to the control eye. Differences between the outcomes for the two procedures were not statistically significant. Morphology of the eyes treated by laser-grid TE revealed dense scarring of perforations around the center of the ligamenta pectinata and loose tissue refilling of the more peripheral openings. CONCLUSIONS: The functional outcome of laser-grid TE in rabbits was similar to that of conventional TE in the short term. Histological examination of microperforations in the area of the trabecular meshwork after 2 weeks indicated that tissue repair was less pronounced than in the more anterior perforations. This morphologic finding may be of importance for non-penetrating glaucoma surgery.

Animals↗
PubMed1984

Argon laser trabeculoplasty following failed trabeculectomy.

Twenty-five patients (30 eyes) with primary open-angle glaucoma post-trabeculectomy with failing blebs and progressive visual field loss were treated with argon laser trabeculoplasty. The average time from filtration surgery to trabeculoplasty was 25.5 +/- 12.0 months. Following trabeculoplasty the mean intraocular pressure dropped significantly from 20.0 +/- 3.7 to 17.2 +/- 4.3 (p less than .005) at a mean follow-up of 14.3 +/- 7.6 months. Sixty-seven percent of eyes had stabilization of visual function. Thirty-three percent were considered treatment failures secondary to progressive visual field loss, sustained rise in intraocular pressure, or further glaucoma surgery. Alteration of the trabecular meshwork resulting from trabeculectomy does not appear to have an adverse effect on laser trabeculoplasty.

Aged↗
PubMed2000

Effect of latrunculin-B on outflow facility in monkeys.

Latrunculin-B (LAT-B), a macrolide derived from the marine sponge Latrunculia magnifica, sequesters monomeric G-actin, leading to the disassembly of actin filaments in cultured cells. In this study, we determined the effect of LAT-B on outflow facility in living monkeys. Total outflow facility was measured by 2-level constant pressure perfusion of the anterior chamber (AC) before and immediately after AC exchange infusion or 2 hr after topical application of LAT-B or vehicle. Both AC exchange infusion and topical application of LAT-B dose- and time-dependently increased outflow facility by two- to four-fold. Those findings suggest that pharmacological disorganization of the actin cytoskeleton in the trabecular meshwork by specific actin inhibitors such as LAT-B may be a useful anti-glaucoma strategy.

Animals↗
PubMed1989

Fibronectin detection in drainage outflow system of human eyes in ageing and progression of open-angle glaucoma.

The content of the fibronectin, an extracellular glycoprotein in the drainage outflow system of human eyes was determined by the indirect immunoperoxidase staining technique. The degree of fibronectin accumulation in ocular tissues was evaluated by quantitative morphometric analysis. It was shown that the fibronectin level was elevated in the ocular drainage outflow system of humans in ageing and was rapidly increased at different stages of primary open-angle glaucoma development. Increased deposit of fibronectin in trabecular tissues, mainly, in the inner wall of Schlemm's canal and juxtacanalicular, or cribriform part of trabecular meshwork, was demonstrated along with ageing and glaucoma disease progression. A hypothesis underlying the glaucomatous process as an adhesive impairment was proposed.

Aged↗
PubMedDate not supplied

Bovine trabecular cells produce TIMP-1 and MMP-2 in response to mechanical stretching.

Bovine trabecular cells in growth phase were exposed to cyclic mechanical stretching of the bottom of a culture dish at a cycle of 30 seconds for 72 hours. The stretched cells produced significantly larger amounts of metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) after 72 hours, compared with cells in nonstretched control. In contrast, TIMP-2 and MMP-9 levels were not influenced by mechanical stretching. Trabecular cells would modify extracellular matrix in response to such mechanical stimuli as bending of trabecular meshwork or aqueous flow by the production of TIMP-1 and MMP-2.

Animals↗
PubMed1999

Advances in glaucoma diagnosis and therapy for the next millennium: new drugs for trabecular and uveoscleral outflow.

Advances in our understanding of the physiology and molecular biology of the trabecular and uveoscleral outflow pathways of the eye will lead to the development of new approaches for glaucoma therapy. Therapies of the future will target the structures and enzymes involved in maintaining cell shape and cell-cell and cell-extracellular matrix interactions. Altering the extracellular matrix in the ciliary muscle has been important in the intraocular pressure lowering effects of prostaglandins and will be developed further as an approach to enhancing outflow through the trabecular meshwork. Gene therapy may be used to enhance or suppress the endogenous targets that are ultimately responsible for the outflow enhancement triggered by these agents.

Animals↗
PubMed1991

Cytochalasin B potentiates epinephrine's outflow facility-increasing effect.

Total outflow facility was determined in both eyes of cynomolgus monkeys by two-level constant pressure perfusion. After a baseline measurement, one eye of the experimental animal received intracameral cytochalasin B (CB); the other eye received vehicle without CB. Twenty minutes later both eyes received intracameral epinephrine (EPI), and 30 min later the outflow facility was again determined. Doses of CB and EPI which were subthreshold when given singly produced significant facility increases when given concurrently. Subthreshold doses of CB given concurrently with a maximal dose of EPI produced significantly larger facility increases than a maximal dose of EPI given alone. A maximal dose of CB produced a larger facility increase than a maximal dose of EPI. Maximal doses of CB and EPI given concurrently produced a larger facility increase than did a maximal dose of EPI alone and had about the same effect as a maximal CB dose given alone. Since CB's facility-increasing effect is likely due to "disruption" of actin filaments in the endothelial cells of the trabecular meshwork and Schlemm's canal and since CB potentiates the facility-increasing effect of EPI, EPI may also act by "disrupting" actin filaments and consequently altering endothelial cell shape.

Actins↗
PubMed1990

Localization of smooth muscle myosin-containing cells in the aqueous outflow pathway.

Cells containing smooth muscle myosin were localized in the human aqueous outflow pathway by immunohistochemical techniques. In the majority of eyes, immunoreactive cells were observed adjacent to the collector channels and slightly distal to the outer wall of Schlemm's canal. In a few eyes, smooth muscle myosin was localized to cells in the juxtacanalicular tissue and the trabecular meshwork. The immunoreactive cells from these regions may be true smooth muscle cells or pericytes, which can contain smooth muscle myosin. No obvious differences were observed in the pattern of distribution of smooth muscle myosin-containing cells in a comparison of age groups. In the majority of eyes, we observed an apparent direct insertion of the longitudinal portion of the ciliary muscle in the corneoscleral meshwork far internal to the scleral spur.

Adolescent↗
PubMed1987

Fibronectin distribution in the rat eye. An immunohistochemical study.

Previous studies of fibronectin (FN) distribution in eye tissue have relied on immunofluorescence (IF) techniques on frozen sections, and have not included the rat. Using rat eyes, a technique was developed for immunoperoxidase (IP) staining of formalin fixed paraffin embedded material, and the results were compared to those obtained by IF. IP was technically more difficult, and required pepsinization of tissue after formalin fixation to obtain consistent results. The optimum pepsin time varied for different structures in the eye. IP offers better tissue preservation and stain resolution. Results with IF were consistent with those observed with the newly applied IP. The distribution of FN in rat eyes was similar though not identical to that reported in other species. Prominent stain was observed in the conjunctiva, basement membrane of the corneal epithelium, corneal stroma, anterior aspect of Descemet's membrane, trabecular meshwork, perivascular stroma of the ciliary body, choroid and retinal blood vessels. Lens structures, vitreous, and internal limiting membrane of the retina were negative.

Animals↗
PubMed1990

Clinical and pathological features of chronic glaucoma in north-east Ghana.

Of 34 consecutive patients with chronic glaucoma seen in north-east Ghana, 22 (65%) were male and seven (21%) were aged under 40 years. Only 17% of eyes had a visual acuity better than 6/18 at presentation. Sixteen of 23 patients who underwent gonioscopy had PAS of which 13 had positive skin snips for onchocerciasis, compared with two out of seven patients with positive skin snips who had open angle glaucoma (p = 0.003). Of 22 trabecular meshworks examined by light microscopy ten (45%) showed marked melanin pigmentation which was more common in younger patients but did not correlate with onchocerciasis infection.

Adolescent↗
PubMed2000

The genetics of open-angle glaucoma: the story of GLC1A and myocilin.

A linkage analysis study was performed on a single large family with juvenile-onset primary open-angle glaucoma (POAG). This led to the recognition that there was a region of chromosome 1q that harboured a gene for juvenile-onset POAG. This chromosomal site was called GLC1A. It was discovered that a gene that produces the protein myocilin resides within this interval and that mutations in myocilin caused most cases of autosomal dominant juvenile-onset POAG. More importantly myocilin mutations also cause up to 4.6% of cases of adult-onset POAG. The prevalence of myocilin mutations is similar regardless of race or geographic location. There are widely variable glaucoma phenotypes depending on the specific mutation in myocilin. Myocilin is expressed in multiple tissues throughout the eye and in many other organs. In the trabecular meshwork the production of myocilin can be induced by the application of topical corticosteroids. The exact function of myocilin in health and disease remains a mystery.

Adult↗
PubMed1991

Suppression of VIP- and terbutaline stimulated aqueous humor flow by increased intraocular pressure in the cynomolgus monkey.

The effect of increased intraocular pressure (IOP) on stimulated aqueous humor flow (AHF) was studied in cynomolgus monkeys. Two experimental series were performed, one with unilateral VIP-treatment (60 micrograms intracamerally) and one with unilateral terbutaline-treatment (10 micrograms.ml-1 perfusion fluid). The AHF was determined with a labelled albumin dilution method, and an artificial increase in IOP was produced by clamping the outlet of the perfusion system, thus causing a net inflow of perfusion fluid. The initial AHF was significantly higher in the VIP-treated eye than in the control eye - 1.568 +/- 0.095 as compared to 1.112 +/- 0.103 microliters.min-1 (P less than or equal to 0.01). The spontaneous IOP was 5.8 +/- 0.4 mmHg (P less than or equal to 0.001) higher in the VIP-treated eye. There was no difference in pseudofacility between the VIP-treated eye (0.063 +/- 0.016 microliter.min-1.mmHg-1) and the control eye (0.065 +/- 0.022 microliter.min-1.mmHg-1), but the total and true outflow facilities were higher in the VIP-treated eye. In the experiments with terbutaline, the initial AHF was 1.729 +/- 0.114 for the experimental eye and 1.262 +/- 0.104 microliters.min-1 for the control eye (P less than or equal to 0.01). The pseudofacility tended to be higher in the terbutaline-treated eye (0.072 +/- 0.026 microliters.min-1.mmHg-1) than in the control eye (0.048 +/- 0.012 microliters.min-1.mmHg-1), but the difference was not statistically significant. There was no difference in total and true outflow facility between the experimental and control eye. The results indicate that the pressure sensitivity of the AHF is independent of the initial level of the AHF. VIP increases true outflow facility, possibly via a direct effect on the trabecular meshwork. VIP also appears to rise the IOP due to an increase in episcleral venous pressure, which could be secondary to vasodilatation in the anterior segment.

Animals↗
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↗
PubMed1990

Retinitis pigmentosa associated with glaucoma--clinical analysis.

A clinical analysis of Retinitis Pigmentosa (RP) was made in 2,789 eyes of 1,400 patients seen over a 5 year period (1983-1987), 64 eyes of 32 cases (2.3%) of RP associated with glaucoma were investigated. Of these 32 cases, the angle closure glaucoma was much more than the open angle glaucoma (30/2). More than half of the 32 cases were without cupping of disk, 5 cases did not have the glaucomatous damage to disk in spite of persistent elevated intraocular pressure for 0.5-5 yrs under the maximum medical therapy. 31 cases (97%) had subnormal blood pressure compared with the normal blood pressure value in different age groups. Histopathologic changes of the trabecular meshwork (TM) of 14 eyes showed a little bit more pigment cells in the TM than normal subjects, no typical features that would obstruct the outflow channels.

Adolescent↗
PubMed1996

Distribution of proteoglycans in the trabecular tissue of eyes with neovascular glaucoma.

We investigated histo-chemically the composition and distribution of proteoglycans in the trabecular tissue of eyes with neovascular glaucoma. Cupromeronic blue in combination with a series of enzyme digestions and nitrous acid treatment were used. The spaces between the trabecular beams were lined by a single layer of vascular endothelium and were filled with red blood cells. A basal lamina and microfibrils were detected just beneath the newly formed vascular endothelial cells. Chondroitin-sulfate- and dermatan-sulfate-type proteoglycans were present in association with collagen fibrils in the extracellular matrix. Heparan-sulfate-type proteoglycans were present in association with the basal lamina of both the vascular endothelial cells and the trabecular cells. It is unlikely that these abnormalities in the type or distribution of proteoglycans in the trabecular meshwork have a major role in the pathogenesis of glaucoma.

Adult↗
PubMed1999

H-7 increases trabecular facility and facility after ciliary muscle disinsertion in monkeys.

PURPOSE: To determine the effects of the serine-threonine kinase inhibitor H-7 on total outflow facility in iridectomized + ciliary muscle (CM)- disinserted, and on trabecular facility in normal, monkey eyes. METHODS: Total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber. Trabecular outflow facility was determined from accumulation in blood of intracamerally infused radioiodinated albumin at two intraocular pressure levels. RESULTS: Three-hundred micromoles of intracameral H-7 doubled facility in iridectomized + CM- disinserted monkey eyes and contralateral iridectomized-only eyes. Four 5-microl drops of 400 mM H-7 applied topically followed 2 hours later by anterior chamber exchange for 10 minutes and intracameral infusion for 90 minutes with 100 microM H-7 increased trabecular and total outflow facility by 135%+/-29% and 105%+/-35% (n 5, P < 0.01, P < 0.05), respectively, compared with contralateral vehicle-treated eyes. CONCLUSIONS: H-7 increases trabecular outflow facility in monkeys by a mechanism independent of the CM, presumably acting directly on the trabecular meshwork.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

Ultrastructural pathology of melanomalytic glaucoma.

A patient presented with a heavily pigmented ciliary body tumour accompanied by diffuse pigmentation of the iris and chamber angle and secondary open angle glaucoma. The case was diagnosed clinically as malignant melanoma and melanomalytic glaucoma, and the eye was enucleated. Routine histopathology, immunohistochemistry, and ultrastructural studies revealed the tumour as being of the spindle cell type with extensive necrosis accompanied by a massive macrophagic response. The iridocorneal angle was heavily infiltrated by large pigmented cells, which were identified as being predominantly melanomacrophages. This is consistent with the few previous descriptions of this condition and confirms the view that the aqueous outflow obstruction is simply a mechanical process. Most of the native trabecular endothelial cells, which had also phagocytosed large quantities of melanin, still maintained their normal relationship to the trabeculae, though there were signs of activation. Immunohistochemistry and electron microscopy revealed the presence of moderate numbers of tumour cells on the iris surface and in the trabecular meshwork distant from the primary tumour site. The importance of these findings to the management of anterior uveal melanomas with secondary open angle glaucoma is discussed.

Ciliary Body↗
PubMed1985

Complications of Nd:YAG laser posterior capsulotomy.

A number of ocular complications are seen to be associated with the use of Nd:YAG laser for posterior capsulotomy after cataract surgery. We have outlined possible hazards to the cornea, trabecular meshwork, vitreous and intraocular lenses and have discussed their consequences. It would appear that the degree of severity of complications is related to the pulse energy used upon the capsule.

Adult↗