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PubMed1997

[Argon laser peripheral iridoplasty and laser iridectomy for plateau iris glaucoma].

OBJECTIVE: To evaluate the therapeutic effects of a combined laser technique for plateau iris glaucoma. METHODS: 20 cases (37 eyes) of early plateau iris glaucoma were treated by a laser technique that included argon laser peripheral iridoplasty and argon + Nd:YAG laser iridectomy. RESULTS: The postoperative follow-up ranged from 8 months to 4 years and 7 months (30 eyes for more than 2 years, mean 2.7 years). 17 cases (32 eyes) obtained satisfactory effects, no acute-attacks were seen in the follow-up, intraocular pressure decreased from 5.8 +/- 1.04 kPa to below 2.74 kPa, peripheral anterior chamber depth increased, angle widened, the iris retracted away from the trabecular meshwork, thus further synechiae of chamber angle were prevented effectively, and the dark room provocative test results turned to negative in 86.7% of cases. CONCLUSION: Argon laser peripheral iridoplasty combined argon + Nd:YAG laser iridectomy may be a safe and effective method for treatment of plateau iris glaucoma.

Adult↗
PubMed1999

[Clinical results of selective laser trabeculoplasty].

PURPOSE: Selective laser trabeculoplasty (SLT) is a new laser procedure using a frequency-doubled Q-switched Nd: YAG laser (wavelength: 532 mm). The laser parameters are set to selectively target pigmented trabecular meshwork (TM) cells without coagulative damage to the TM structure or non-pigmented cells. We investigated the safety and efficacy of SLT in lowering intraocular pressure (IOP). SUBJECTS AND METHOD: Sixty-seven eyes of 67 patients with uncontrolled open angle glaucoma were treated with the Coherent Selecta 7000 (Coherent Inc., Palo Alto, CA). Nineteen of 67 patients had previously received argon laser trabeculoplasty (ALT). A total of approximately 60 non-overlapping spots were placed over 180 degrees of the TM ranging from 0.5 to 1.0 mJ per pulse. The maximum energy level at which no bubble formation was observed determined choice. RESULTS: The average preoperative IOP was 22.4 mmHg. Six months after the operation, mean IOP reduction was 4.4 mmHg, and mean outflow pressure (OP) reduction was 38.1%. One month after the operation 68.7% of patients responded to treatment with an OP reduction of at least 20% ("responders"). Transient IOP elevation of 5 mmHg or greater was seen in 25.4% of patients. The success rate at 6 months after operation was 64.6% for all patients (67 eyes) and 78.2% for the responders (46 eyes). An analysis using a Cox proportional hazard model showed that a low preoperative IOP was the significant determinant for success, and the hazard ratio for the IOP increase of 5 mmHg was 2.12. Other factors such as age, gender, past history of ALT, and goniopigment were not significantly related to success. CONCLUSION: SLT appears to be a safe and effective way to lower IOP.

Adult↗
PubMed1999

Localization of cannabinoid CB1 receptors in the human anterior eye and retina.

PURPOSE: To determine the presence and distribution of CB1 cannabinoid receptors within the human eye. METHODS: A subtype-specific affinity-purified polyclonal antibody to the cannabinoid CB1 receptor was used to determine CB1 localization. Postmortem human eyes were fixed in methacarn and embedded in paraffin. Sagittal sections were mounted on slides and immunostained using antibodies to the CB1 receptor. Antibody binding was detected either by using peroxidase conjugated secondary antibodies and developing with diaminobenzidine or by using fluorescent secondary antibodies. RESULTS: Strong CB1 receptor labeling was detected in the ciliary epithelium, the corneal epithelium, and endothelium of the anterior human eye. Strong-to-moderate levels of CB1 staining were found in the trabecular meshwork and Schlemm's canal. Moderate labeling was detected in the ciliary muscle and in the blood vessels of the ciliary body. Moderate-to-light labeling also was detected in the sphincter papillae of the anterior human eye. Staining for CB1 receptors also was detected in human retina. The two synaptic layers of the retina and the inner and outer plexiform layers, were both moderately stained for CB1. In addition, moderate labeling was detected in the inner nuclear layer, and the ganglion cell layer. Strong labeling was detected in the outer segments of photoreceptors. No staining was observed in the corneal stroma or in the choroid. CONCLUSIONS: The wide distribution of cannabinoid CB1 receptors in both the anterior eye and the retina of humans suggests that cannabinoids influence several different physiological functions in the human eye.

Adult↗
PubMed1976

Iris and anterior chamber involvement in leukemia.

A case of acute lymphocytic leukemia is described with bilateral ocular involvement, including iris, trabecular meshwork, and anterior chamber. Microscopic findings are correlated with clinical findings. All cases reported to date (5) in the American literature with microscopically confirmed leukemic iris infiltrate have been of acute lymphocytic leukemia.

Anterior Chamber↗
PubMed2000

[Familial amyloid polyneuropathy type I complicated by chronic glaucoma: 3 cases].

PURPOSE: We report 3 cases of familial amyloid polyneuropathy type I (FAP) with amyloid infiltration of the vitreum and glaucoma. PATIENTS AND METHODS: We reviewed the records of three patients, 2 females and one male, aged 41, 47 and 83 years respectively. The 3 patients had familial amyloid polyneuropathy type I with vitreous infiltration and open angle glaucoma. The two women underwent a liver graft four years earlier. Vitrectomy allowed confirmation of the diagnosis in the 83-year-old patient. Two patients underwent trabeculectomy, histological analysis of the iris and the trabeculum was obtained for one patient. RESULTS: The tree patients presented a polyneuropathy, vitreous infiltration and open angle glaucoma. Results of light microscopy of the iris and the trabeculum showed amyloid deposits in the iris and the trabecular meshworks. CONCLUSION: Familial amyloid polyneuropathy is a hereditary disease which may have a wide range of ocular manifestations. Glaucoma is among the most serious complications of familial amyloid polyneuropathy.

Adult↗
PubMed2000

Herpes simplex virus-mediated gene delivery to the rodent visual system.

PURPOSE: To determine the types of cells in the visual system of the mouse and rat that can express a transgene delivered by an attenuated replication competent Herpes simplex virus-1 (HSV-1) vector. METHODS: C57/BL6 x BALB/C mice and Albino rats were treated with 1 x 10(7) pfu of the HSV-1 ribonucleotide reductase mutant (hrR3) expressing the Escherichia coli lacZ gene. The hrR3 virus was delivered by topical application to the cornea, intravitreal (IV) injection, intracameral injection (IC), or stereotactic injection into the visual cortex (VC). At specified times postinfection, animals were killed and tissues were removed, fixed, sectioned, and stained with X-gal or hematoxylin and eosin for histochemical and histopathologic examination. RESULTS: Topical delivery after corneal scarification in both mouse and rat resulted in lacZ expression in 25% of the corneal epithelial cells and 25% of the retinal pigment epithelium (RPE) cells. Topical application without concurrent scarification also resulted in transgene delivery to 20% of the RPE cells of the rat but not the mouse. IV injection resulted in expression primarily in RPE cells, with up to 100% of the cells expressing lacZ in the mouse and rat. Other cells expressing the transgene included ciliary body (CB) and optic nerve cells. Up to 25% of the retinal ganglion cells in the rat expressed lacZ, but only rarely in mice. IC delivery in rats resulted in expression in trabecular meshwork, CB cells, RPE, and iris epithelium. Injection into area 17 of the rat VC resulted in efficient labeling of the VC neurons and neurons in the lateral geniculate nucleus without any evident pathology or inflammation. Neither inflammation nor disease pathology was observed in either the mouse or rat after any route of delivery. CONCLUSIONS: It was demonstrated that the hrR3 HSV-1 virus can deliver a functioning gene to several cell types in the eye and neurons in the VC and that the virus can move via retrograde transport to nuclei that project to the VC.

Animals↗
PubMed2000

Direct effects of muscarinic agents on the outflow pathways in human eyes.

PURPOSE: Recent studies demonstrating the presence of muscarinic receptors and contractile-like cells in the trabecular meshwork tissue and/or cell cultures from human eyes suggest the possibility that there may be a direct effect of muscarinic agonists on outflow facility. The present studies were conducted to determine whether muscarinic agonists could change outflow facility in perfused human ocular anterior segments, which lack an intact ciliary muscle. METHODS: Human eyes were dissected and perfused according to previously described methods. A steady state baseline facility was established for 90 minutes, after which up to four sequential concentrations ranging from 10(-9) to 10(-3) M of pilocarpine, aceclidine, or carbachol were added to the perfusion medium. In other studies, 10(-6) M atropine was perfused alone followed by 10(-7) M carbachol with 10(-6) M atropine, whereas fellow control eyes received carbachol alone. Outflow facility was measured for 60 minutes after each drug addition. The outflow facility measurement in each eye after drug administration was compared with the baseline measurement. RESULTS: Outflow facility increased from baseline facility in eyes treated with pilocarpine, aceclidine, or carbachol at lower concentrations (10(-9) to 10(-6) M) but remained unchanged at higher concentrations (10(-4) to 10(-2) M). The effects of carbachol at 10(-7) M were completely blocked by atropine. CONCLUSIONS: Muscarinic agonists increase outflow facility in human eyes by a direct stimulation of the outflow tissues in the absence of an intact ciliary muscle. This effect is biphasic, occurring at concentrations of 10(-6) M and lower with no effect at higher concentrations.

Aged↗
PubMed2000

Latrunculins' effects on intraocular pressure, aqueous humor flow, and corneal endothelium.

PURPOSE: To determine the effects of latrunculin (LAT)-A or -B on intraocular pressure (IOP), aqueous humor flow (AHF), anterior chamber (AC) protein concentration ([protein]AC), corneal endothelial permeability and morphology, and corneal thickness in living cynomolgus monkeys. METHODS: Topical LAT-A or LAT-B was administered to one eye, and vehicle to the other. IOP was measured by Goldmann tonometry, AHF and corneal endothelium transfer coefficient (ka) by fluorophotometry, [protein]Ac by Lowry assay, corneal endothelial cell morphology by specular microphotography, and corneal thickness by ultrasound pachymetry. RESULTS: LAT-A began to lower IOP at 6 hours and maximally reduced IOP by 4.6 mm Hg at 9 hours. LAT-B lowered IOP within 1 hour and maximally reduced IOP by 3.1 mm Hg at 6 hours. LAT-A increased AHF by 87% for 3 hours and increased ka by 94% over 6 hours; LAT-B increased ka by 39% over 6 hours without affecting AHF. LAT-A increased IV fluorescein entry into the cornea approximately 10 fold, but did not affect IV fluorescein entry into the AC. LAT-A increased [protein]AC by 25% at 2 hours but not 5.5 hours. LAT-B variably and insignificantly increased [protein]AC: at 1 hour but not at 6.5 hours. LAT-A induced extensive corneal endothelial pseudoguttata within 1 hour, with normal cell counts by 7 days. LAT-B increased central corneal thickness maximally by 47 microm at 3.5 hours. CONCLUSIONS: LAT-A and -B significantly reduced IOP and were consistent in their facility-increasing effect, indicating that pharmacologic disorganization of the actin cytoskeleton in the trabecular meshwork by latrunculins may be a useful antiglaucoma strategy. However, effects on corneal endothelium or ciliary epithelium are a potential safety issue.

Animals↗
PubMed2000

Localization of thrombomodulin in the anterior segment of the human eye.

PURPOSE: To localize thrombomodulin (TM) in the anterior segment of the human eye. TM is a vascular endothelial cell surface glycoprotein that acts as a cofactor for the thrombin-catalyzed activation of the anticoagulant protease zymogen, protein C. METHODS: Immunohistochemical methods were used to detect TM expression in corneal epithelial cells, the lens epithelial cells, and other cells in the anterior segment of the eye. The expression of TM was also examined in cultured human corneal epithelial cells. RESULTS: TM was expressed in corneal epithelial cells, corneal endothelial cells, and nonpigmented ciliary epithelial cells, which are in direct contact with the aqueous humor. TM was also expressed in cultured corneal epithelial cells and showed cofactor activity. The amount of the antigen in the cultured corneal cells was approximately one tenth of that in human umbilical vein endothelial cells, but its specific cofactor activity (75%) was comparable to that of TM in human umbilical vein endothelial cells. The trabecular meshwork and endothelial cells lining Schlemm's canal also showed positive staining for TM. CONCLUSIONS: The TM in the cells that are in contact with the aqueous humor appears to be involved in maintaining the fluidity of the aqueous humor. In contrast, TM in cells that are not in contact with the aqueous humor may function in regulating cell proliferation and/or differentiation.

Adult↗
PubMed2000

[The mechanisms of neuronal death in glaucoma].

The current therapy of glaucoma (drugs, LASER, surgery) acts mainly on the trabecular meshwork and on the ciliary body. The loss of the visual function in glaucoma is however determined by the disfunction and death of the ganglion cells. The main theories trying to explain the death of the ganglion cells in glaucoma are analyzed. Their practical value is represented by the finding of the ideal neuroprotective drug.

Animals↗
PubMed2001

Inhibition of Na(+)/K(+)-atpase by endothelin-1 in human nonpigmented ciliary epithelial cells.

Endothelin-1 (ET-1), a potent vasoconstrictor, lowers intraocular pressure in mammals, either by enhancing the outflow of aqueous humor (AH) via the trabecular meshwork and Schlemm's canal or by reducing AH formation at the ciliary epithelium. Aqueous humor production occurs by passive diffusion of water coupled with active transport of ions, mainly involving Na(+):K(+):2Cl(-) cotransporter and Na(+)/K(+)-ATPase pump from serosal to aqueous side. Presently, we have evaluated the effects of ET-1 on Na(+):K(+):2Cl(-) cotransport and Na(+)/K(+)-ATPase activity in HNPE cells using (86)Rb(+) uptake. ET-1 (100 pM-100 nM) decreased mean (86)Rb(+) uptake by 15% during a 15-min uptake period. ET-1's effect was not prevented by BQ610, an ET(A) receptor antagonist, but was blocked by BQ788, an ET(B) receptor antagonist. ET-1's effect was mimicked by sarafotoxin, an ET(B) agonist. ET-1-induced reduction in (86)Rb(+) uptake was additive with bumetanide, a selective inhibitor of Na(+):K(+):2Cl(-) cotransporter but not with ouabain, a selective inhibitor of the Na(+)/K(+)-ATPase. ET-1 did not affect iberiotoxin-sensitive maxi K(+) channels. This suggests that ET-1-induced reduction in (86)Rb(+) uptake is mediated through the inhibition of the Na(+)/K(+)-ATPase via an ET(B)-like receptor. These findings are consistent with an ET-1 effect on active ion transport activity in HNPE cells that could explain the reduction in aqueous humor production and the lowering of intraocular pressure.

Antihypertensive Agents↗
PubMed2001

Natural therapies for ocular disorders, part two: cataracts and glaucoma.

Pathophysiological mechanisms of cataract formation include deficient glutathione levels contributing to a faulty antioxidant defense system within the lens of the eye. Nutrients to increase glutathione levels and activity include lipoic acid, vitamins E and C, and selenium. Cataract patients also tend to be deficient in vitamin A and the carotenes, lutein and zeaxanthin. The B vitamin riboflavin appears to play an essential role as a precursor to flavin adenine dinucleotide (FAD), a co-factor for glutathione reductase activity. Other nutrients and botanicals, which may benefit cataract patients or help prevent cataracts, include pantethine, folic acid, melatonin, and bilberry. Diabetic cataracts are caused by an elevation of polyols within the lens of the eye catalyzed by the enzyme aldose reductase. Flavonoids, particularly quercetin and its derivatives, are potent inhibitors of aldose reductase. Glaucoma is characterized by increased intraocular pressure (IOP) in some but not all cases. Some patients with glaucoma have normal IOP but poor circulation, resulting in damage to the optic nerve. Faulty glycosaminoglycan (GAG) synthesis or breakdown in the trabecular meshwork associated with aqueous outflow has also been implicated. Similar to patients with cataracts, those with glaucoma typically have compromised antioxidant defense systems as well. Nutrients that can impact GAGs such as vitamin C and glucosamine sulfate may hold promise for glaucoma treatment. Vitamin C in high doses has been found to lower IOP via its osmotic effect. Other nutrients holding some potential benefit for glaucoma include lipoic acid, vitamin B12, magnesium, and melatonin. Botanicals may offer some therapeutic potential. Ginkgo biloba increases circulation to the optic nerve; forskolin (an extract from Coleus forskohlii) has been used successfully as a topical agent to lower IOP; and intramuscular injections of Salvia miltiorrhiza have shown benefit in improving visual acuity and peripheral vision in people with glaucoma.

Cataract↗
PubMed2001

Optimal procedure for extracting RNA from human ocular tissues and expression profiling of the congenital glaucoma gene FOXC1 using quantitative RT-PCR.

PURPOSE: To develop methods for obtaining high quality RNA from human donor eyes and to determine the expression profile of the congenital glaucoma gene FOXC1 in human ocular tissues. METHODS: To obtain high quality RNA from donor eyes, several different preservation methods were tested including storing eyes on ice, freezing eyes, and placing eyes in the commercial fixative RNAlaterTM prior to dissection and RNA extraction. Nine different ocular tissues from human donors were dissected and examined. Pigment-free total RNA was isolated and used for quantitative real-time RT-PCR using FOXC1 and GAPDH (internal standard) primers to assess the quality and expression of FOXC1. RESULTS: An expression profile of FOXC1 in human ocular tissues was determined using quantitative PCR of RNA isolated using a simple and effective procedure for ocular tissue preservation and pigment-free RNA isolation. Higher quality RNA was obtained from human donor eyes preserved in RNAlaterTM compared to RNA extracted from eyes stored on ice or frozen at -80 degrees C. RNA extraction techniques that removed interfering pigment from ocular tissues produced RNA that could be easily amplified by PCR. In the adult human eye, expression of FOXC1 was greatest in the trabecular meshwork (TM) followed by the optic nerve head, choroid/RPE, ciliary body, cornea, and iris. FOXC1 expression levels were much lower in other non-ocular human tissues, such as liver, muscle, lung, heart, and kidney. CONCLUSIONS: Using an optimized donor eye preservation method and tissue RNA isolation procedure, we show that the FOXC1 transcription factor gene, which is known to be associated with developmental glaucoma, also may have an important role in the adult eye.

Aged↗
PubMed2000

[Laser trabeculoplasty--present and future perspectives].

Laser trabeculoplasty has been used in the treatment of various types of glaucoma for nearly 20 years. It's intraocular pressure lowering effect through enhancement of aqueous outflow is well documented. In spite of this, the precise effect of laser trabeculoplasty in the trabecular meshwork is only partially understood. It is related to laser wave length, laser power, burns location, number of shots etc. The effectiveness of laser trabeculoplasty diminishes over time, but can be renewed with re-treatment. Laser trabeculoplasty has connected with minimum complications and it is most effective in patients with primary open-angle glaucoma, pigmentary glaucoma and the exfoliation syndrome glaucoma, though the long-term results of this microsurgery laser treatment are not quite indisputable.

Glaucoma↗
PubMed2001

Induction of heat shock protein 72 protects retinal ganglion cells in a rat glaucoma model.

PURPOSE: To investigate whether heat shock protein (Hsp) 72 is induced in retinal ganglion cells (RGCs) in experimental rat glaucoma and whether the induction of Hsp72 by heat stress or zinc (Zn(2+)) administration can increase survival of RGCs in the model. METHODS: Intraocular pressure (IOP) was elevated unilaterally in Wistar rats with argon laser irradiation of the trabecular meshwork 5 days after intracameral injection of india ink. Immunohistochemical staining for Hsp72 was performed. The rats with elevated IOP were treated with heat stress once a week (six rats) or intraperitoneal injection of zinc (10 mg/kg) every two weeks (six rats). Untreated rats with elevated IOP served as a control group (six rats). Quercetin, an inhibitor of Hsp expression was injected in the rats with heat stress (six rats) and zinc injection (seven rats). Subsequent to 4 weeks of IOP elevation, RGCs were counted. RESULTS: The IOP increase compared with the contralateral eyes was 48% +/- 4% throughout the study period. Hsp72 was detected only in the eyes with elevated IOP at 1 and 2 days and was weakly detected at 1 week of IOP elevation. A single administration of zinc strongly induced Hsp72 in RGCs of rats with elevated IOP for 2 weeks. Treatment with heat stress or zinc in rats with elevated IOP increased RGC survival after 4 weeks of IOP elevation, compared with the untreated control group (P = 0.004, n = 6). Quercetin reversed the positive effect of heat stress or zinc injection on RGC survival. CONCLUSIONS: These results demonstrate the possibility of a novel therapeutic approach to glaucoma through an enhanced induction of the endogenous heat shock response.

Animals↗
PubMed2001

Reduced TIGR/myocilin protein in the monkey ciliary muscle after topical prostaglandin F(2alpha) treatment.

PURPOSE: Mutations in the trabecular meshwork inducible glucocorticoid response (TIGR) gene, also known as myocilin, have recently been linked to some forms of glaucoma. Recent studies have shown that TIGR protein also is expressed in the ciliary muscle. Because uveoscleral outflow, which traverses the ciliary muscle, is increased by prostaglandins (PGs), the present study assessed whether topical PGs alter the amount of TIGR protein within the ciliary muscle. METHODS: Vehicle was topically applied to one eye, and 2 microg PGF(2alpha)-isopropyl ester (PGF(2alpha)-IE) was applied to the other eye of cynomolgus monkeys twice daily for 5 days. Pressure reductions of 5 mm Hg in the PGF(2alpha)-IE-treated eyes were confirmed. The eyes were then fixed and paraffin sections were cut from each eye. The distribution of TIGR protein in the ciliary muscle was determined by confocal scanning laser microscopy. Additional sections were immunostained with a polyclonal antibody to recombinant TIGR protein or with a polyclonal antibody to a synthetic peptide corresponding to the leucine zipper region within the TIGR protein. Staining intensity in the ciliary muscle was assessed by measuring optical density (OD) along two line segments overlying the ciliary muscle, by using a high-resolution imaging densitometer. RESULTS: TIGR protein immunoreactivity was observed in ciliary muscle fibers throughout the ciliary muscle. Extracellular TIGR immunoreactivity colocalized with collagen type IV immunoreactivity. Intracellular staining also was present. Immunoreactivity was less intense in the sections from the PGF(2alpha)-IE-treated eyes compared with the vehicle-treated eyes. This was reflected in the reduction of mean OD scores in each monkey. Overall, the reduction of mean OD scores in the treated eyes was 42.1% +/- 9.9% (P < 0.005) with the anti-recombinant TIGR antibody and 27.3% +/- 10.4% with the anti-TIGR peptide antibody (P < 0.005). CONCLUSIONS: TIGR protein immunoreactivity was present both intracellularly and extracellularly in the ciliary muscle of the cynomolgus monkey. This suggests that extracellular TIGR protein is in contact with aqueous humor in the uveoscleral outflow pathway. Moreover, IOP-lowering topical PGF(2alpha)-IE treatment decreases the amount of TIGR protein in the ciliary muscle.

Administration, Topical↗
PubMed2001

Expression and putative role of 11 beta-hydroxysteroid dehydrogenase isozymes within the human eye.

PURPOSE: The human eye is an important target tissue for steroid hormones, and glucocorticoids have been implicated in the pathogenesis of ocular disease, including glaucoma. In peripheral tissues, corticosteroid hormone action is regulated at a prereceptor level through the activity of the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isozymes: an oxo-reductase (11 beta-HSD1) that activates cortisol (F) from cortisone (E) and a dehydrogenase (11 beta-HSD2) that inactivates F to E. The purpose of this study was to analyze the expression and putative role of 11 beta-HSD within the human eye. METHODS: Immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) studies were performed on sections of human ocular tissues, surgical trabecular meshwork (TM) specimens and a ciliary nonpigmented epithelial (NPE) cell-line. Free F and E concentrations in aqueous humor were determined by gas chromatography-mass spectrometry (GC/MS). IOP was measured in eight male volunteers before and after oral ingestion of carbenoxolone (CBX), a known inhibitor of 11 beta-HSD. RESULTS: 11 beta-HSD1 was expressed in the basal cells of the corneal epithelium and the NPE. 11 beta-HSD2 was restricted to the corneal endothelium. RT-PCR revealed mRNA for only the glucocorticoid receptor (GR) in the TM specimens, whereas GR, mineralocorticoid receptor and 11 beta-HSD1 mRNAs were all present in the NPE cell line. The demonstration of free F in excess of E (F/E 14:1) in the aqueous humor suggested predominant 11 beta-HSD1 activity. Compared with baseline (14.7 +/- 1.06 mm Hg, mean +/- SD), the IOP decreased significantly on both the third and seventh days of CBX ingestion (12.48 +/- 1.11 mm Hg, P < 0.0001 and 11.78 +/- 1.50 mm Hg, P < 0.0001, respectively). CONCLUSIONS: These results suggest that the 11 beta-HSD1 isozyme may modulate steroid-regulated sodium transport across the NPE, thereby influencing IOP.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Changes in Thy1 gene expression associated with damaged retinal ganglion cells.

PURPOSE: The temporal series of molecular events that occur in dying retinal ganglion cells is poorly understood. We have examined the change in expression of a normally-expressed ganglion cell marker gene, Thy1, relative to the kinetics of cell loss caused by acute and chronic damaging stimuli. METHODS: For acute experiments, mice were subjected to optic nerve crush or intravitreal injections of N-methyl-D-aspartate (NMDA) to induce ganglion cell death. RNase protection analysis was used to quantify Thy1 mRNA levels from total retina RNA and in situ hybridization was used to monitor the pattern of Thy1 positive cells. Changes in Thy1 expression were compared to the time course of cell loss induced by each treatment. To induce elevated intraocular pressure (IOP), the episcleral veins of rats were injected with hypertonic saline, which scleroses Schlemm's Canal and the trabecular meshwork. Elevated IOP was monitored every day for 35 days after which the animals were sacrificed and the retinas harvested for quantitative RT-PCR or fixed for in situ hybridization studies. Evaluation of glaucomatous damage caused by elevated IOP was determined from histological sections of the optic nerves of all rat eyes. RESULTS: After optic nerve crush, Thy1 mRNA levels decreased within 24 h, although the number of expressing cells did not decline until 7 days. Both measures showed a loss of Thy1 well in advance of cell loss, which was detected by 2 weeks after surgery. This change in expression was not dependent on execution of the cell death program since a similar decrease was detected in Bax-/- ganglion cells, which are resistant to cell death induced by optic nerve crush. Thy1 mRNA levels and the number of expressing cells also decreased within 6 h after NMDA injection, in advance of cell loss, which was detected by 24 h. Similarly, elevated intraocular pressure was associated with a decrease in mRNA and expressing cells in a pressure-dependent manner. In moderately hypertensive rat eyes, the number of cells expressing Thy1 decreased before significant cell loss in the retina. Virtually no Thy1-expressing cells were detected in eyes with severe disease. CONCLUSIONS: Thy1 mRNA abundance and expressing cells, decreased in advance of detectable ganglion cell loss caused by three different modalities of damage. This change is independent of the committed step of cell death.

Animals↗