Protection of the Retinal Ganglion Cells: Intravitreal Injection of Resveratrol in Mouse Model of Ocular Hypertension.

Purpose: To investigate the efficacy of intravitreal administration of resveratrol (RSV) in a microbead-induced high intraocular pressure (IOP) murine model for glaucoma. Methods: Experiments were performed using adult C57BL/6JJcl mice. Polystyrene microbeads were injected into the anterior chamber to induce IOP elevation. Retinal flat-mounts and sections were assessed by immunohistochemistry to detect the expression of reactive oxygen species and acetyl-p53 in retinal ganglion cells (RGCs), brain-derived neurotrophic factor (BDNF) in Müller glial cells (MGCs), and the receptor tropomyosin receptor kinase B (TrkB) in RGCs. Light cycler real-time PCR was also used for confirming gene expression of BDNF in primary cultured MGCs exposed to RSV. Results: Microbeads induced high IOP followed by RGC death and axon loss. Administration of RSV rescued RGCs via decreased reactive oxygen species generation and acetyl-p53 expression in RGCs and upregulated BDNF in MGCs and TrkB expression in RGCs, which exhibited a strong cytoprotective action against cell death through multiple pathways under high IOP. Conclusions: Our data suggest that administration of RSV may delay the progress of visual dysfunction during glaucoma and may therefore have therapeutic potential.

Posttreatment Intervention With Lycium Barbarum Polysaccharides is Neuroprotective in a Rat Model of Chronic Ocular Hypertension.

Purpose: To investigate the neuroprotective effects of Lycium barbarum polysaccharides (LBP) against chronic ocular hypertension (OHT) in rats and to consider if effects differed when treatment was applied before (pretreatment) or during (posttreatment) chronic IOP elevation. Methods: Sprague-Dawley rats (10-weeks old) underwent suture implantation around the limbus for 15 weeks (OHT) or 1 day (sham). Four experimental groups were studied, three OHT groups (n = 8 each) treated either with vehicle (PBS), LBP pretreatment or posttreatment, and a sham control (n = 5) received no treatment. LBP (1 mg/kg) pre- and posttreatment were commenced at 1 week before and 4 weeks after OHT induction, respectively. Treatments continued up through week 15. IOP was monitored twice weekly for 15 weeks. Optical coherence tomography and ERG were measured at baseline, week 4, 8, 12, and 15. Eyes were collected for ganglion cell layer (GCL) histologic analysis at week 15. Results: Suture implantation successfully induced approximately 50% IOP elevation and the cumulative IOP was similar between the three OHT groups. When compared with vehicle control (week 4: -23 ± 5%, P = 0.03), LBP pretreatment delayed the onset of retinal nerve fiber layer (RNFL) thinning (week 4, 8: -2 ± 7%, -11 ± 3%, P > 0.05) and arrested further reduction up through week 15 (-10 ± 4%, P > 0.05). LBP posttreatment intervention showed no significant change in rate of loss (week 4, 15: -25 ± 4.1%, -28 ± 3%). However, both LBP treatments preserved the retinal ganglion cells (RGC) and retinal functions up to week 15, which were significantly reduced in vehicle control. Conclusions: LBP posttreatment arrested the subsequent neuronal degeneration after treatment commencement and preserved RGC density and retinal functions in a chronic OHT model, which was comparable with pretreatment outcomes.

GRGM-13 comprising 13 plant and animal products, inhibited oxidative stress induced apoptosis in retinal ganglion cells by inhibiting P2RX7/p38 MAPK signaling pathway.

OBJECTIVE: To determine the effectiveness of GRGM-13 on oxidative stress induced apoptosis of retinal ganglion cells (RGCs) and revealed its possible mechanism. MATERIALS AND METHODS: Caspase-3 activity, MDA level, and glutathione peroxidase level were detected by Caspase-3 assay kit, Lipid Peroxidation MDA Assay Kit, and Total Glutathione Peroxidase Assay Kit, respectively. Protein levels of Bax, Bcl-2, p-p38 and p38 were observed by Western Blot. Reactive oxygen species assay kit was used to determine intracellular ROS level. Apoptotic cells were measured by flow cytometry. RESULTS: GRGM-13 inhibited apoptosis of RGCs and ROS level in rat retinal tissue and RGC-5 cells, and the decrease degree strengthened with the increase of GRGM-13 concentration. In addition, ROS upregulated p-p38 expression, while GRGM-13 reversed this effect. We also found that p38 inhibitor SB202190 did not change L-glutamate (Glu) or H2O2-induced ROS level, while SB202190 inhibited apoptosis of RGC-5 cells. Finally, we observed that P2 × 7R agonist BzATP reversed the inhibition effect of GRGM-13 on RGC-5 cell apoptosis, ROS level and p-p38 expression, while si-P2 × 7R inhibited oxidative stress-induced phosphorylation of p38. CONCLUSION: GRGM-13 could inhibit oxidative stress-induced RGCs apoptosis via inhibiting P2RX7/p38 MAPK pathway, which revealed the possible mechanism of GRGM-13 on stress-induced RGCs apoptosis and provided new Chinese medicine for the treatment of glaucoma.

Nanostructured lipid carriers for intraocular brimonidine localisation: development, in-vitro and in-vivo evaluation.

Brimonidine ocular hypotensive effect can be enhanced by increasing residence time and corneal penetration. The current work aimed to formulate, evaluate and compare nanostructured lipid carriers (NLCs) to solid lipid nanoparticles (SLNs) and commercial eye drops for controlled brimonidine delivery. NLCs prepared by modified high shear homogenisation were spherical with a mean size of 151.97 ± 1.98 nm, negative zeta potential (ZP) of -44.2 ± 7.81 mV, % entrapment efficiency (EE) of 83.631 ± 0.495% and low crystallinity index (CI) (17.12%), indicating a better drug incorporation. Moreover, they kept stable during storage at 4 °C for 3 months. Permeability coefficient of NLCs was 1.227 folds higher than that of SLNs. Histological examination revealed localisation of NLCs in the anterior ocular chamber. NLCs revealed the most sustained and highest intraocular pressure (IOP) lowering activity (-13.14 ± 1.28 mmHg) in rabbits. In conclusion, NLCs is a promising approach for IOP reduction compared to eye drops and SLNs.

Neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

PURPOSE: Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss, and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in blindness. Brn3b is a class-4 POU domain transcription factor that plays a key role in RGC development, axon outgrowth, and pathfinding. Previous studies suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The goal of this study was to determine if adeno-associated virus (AAV)-directed overexpression of the Brn3b protein could have neuroprotective effects following elevated IOP-mediated neurodegeneration. METHODS: Intraocular pressure was elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the IOP-elevated eyes were intravitreally injected with AAV constructs encoding either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV-hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity markers and neuroprotection was assessed by RGC counts and visual acuity tests. RESULTS: Adeno-associated virus-mediated expression of the Brn3b protein in IOP-elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP-43), actin binding LIM protein (abLIM) and acetylated α-tubulin (ac-Tuba) both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b-injected rats compared with those of the IOP-elevated rAAV-hsyn-GFP- injected rats. Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored the visual optomotor response in IOP-elevated rat eyes. CONCLUSIONS: Adeno-associated virus-mediated Brn3b protein expression may be a suitable approach for promoting neuroprotection in animal models of glaucoma.

Neuroprotective effect of curcumin against oxidative damage in BV-2 microglia and high intraocular pressure animal model.

PURPOSE: The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. In this study, we aim to evaluate the antioxidant effects of curcumin in BV-2 microglia oxidative damage and assess its neuroprotective effects in a chronic high IOP rat model. METHODS: BV-2 microglia cell line was used in an in vitro study and Wistar rats were used in an in vivo study. Cultured BV-2 microglia cells were pretreated with 10, 1, or 0.1 µM curcumin for 1 h, and sustained oxidative stress was induced by subjecting BV-2 microglia to 200 µM hydrogen peroxide (H2O2) for 24 h. MTT assay was used to determine cell viability. Changes of intracellular reactive oxygen species (ROS) and apoptosis were analyzed by flow cytometry. Three episcleral veins were cauterized to induce high IOP in Wistar rats and measured by Tonopen. After 6 weeks of treatment with curcumin (10 mg/kg/day) by intragastric administration, surviving of retinal ganglion cells was quantified. Activation of caspase 3, cytochrome c, BAX, and BCL2 was quantified by Western blotting both in BV-2 microglia and in animal model. Data were analyzed with the GraphPad Prism 5.0 software, and P<0.05 was considered to be statistically significant. RESULTS: The in vitro study showed that when BV-2 microglia was pretreated with curcumin, the cell viability increased and the intracellular ROS and apoptosis significantly decreased. In the in vivo study, chronic mild IOP elevation was induced for 4 weeks. In the curcumin-treated group, curcumin protected rat BV-2 microglia from death significantly. In both H2O2-treated BV-2 microglia and glaucoma models, caspase 3, cytochrome c, and BAX were downregulated and BCL2 was upregulated in the curcumin-treated group. CONCLUSIONS: Curcumin affords neuroprotective effects by inhibiting oxidative damage and could be a new or adjunctive treatment for glaucoma.

Protection of retinal ganglion cells and retinal vasculature by Lycium barbarum polysaccharides in a mouse model of acute ocular hypertension.

Acute ocular hypertension (AOH) is a condition found in acute glaucoma. The purpose of this study is to investigate the protective effect of Lycium barbarum polysaccharides (LBP) and its protective mechanisms in the AOH insult. LBP has been shown to exhibit neuroprotective effect in the chronic ocular hypertension (COH) experiments. AOH mouse model was induced in unilateral eye for one hour by introducing 90 mmHg ocular pressure. The animal was fed with LBP solution (1 mg/kg) or vehicle daily from 7 days before the AOH insult till sacrifice at either day 4 or day 7 post insult. The neuroprotective effects of LBP on retinal ganglion cells (RGCs) and blood-retinal-barrier (BRB) were evaluated. In control AOH retina, loss of RGCs, thinning of IRL thickness, increased IgG leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of IRL thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein and the recovery of the blood vessel density when compared with vehicle-treated AOH retina. Moreover, we found that LBP provides neuroprotection by down-regulating RAGE, ET-1, Aß and AGE in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. The present study suggests that LBP could prevent damage to RGCs from AOH-induced ischemic injury; furthermore, through its effects on blood vessel protection, LBP would also be a potential treatment for vascular-related retinopathy.

Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.

Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP) characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1) is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ET(B)) receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ET(B) receptors in the retina, mainly in retinal ganglion cells (RGCs), nerve fiber layer (NFL), and also in the inner plexiform layer (IPL) and inner nuclear layer (INL). To determine the role of ET(B) receptors in neurodegeneration, Wistar-Kyoto wild type (WT) and ET(B) receptor-deficient (KO) rats were subjected to retrograde labeling with Fluoro-Gold (FG), following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ET(B) receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma.

Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2α agonist, in preclinical models.

The aim of the study was to investigate the ocular hypotensive activity of a nitric oxide (NO)-donating latanoprost, BOL-303259-X, following topical administration. The effect of BOL-303259-X (also known as NCX 116 and PF-3187207) on intraocular pressure (IOP) was investigated in monkeys with laser-induced ocular hypertension, dogs with naturally-occurring glaucoma and rabbits with saline-induced ocular hypertension. Latanoprost was used as reference drug. NO, downstream effector cGMP, and latanoprost acid were determined in ocular tissues following BOL-303259-X administration as an index of prostaglandin and NO-mediated activities. In primates, a maximum decrease in IOP of 31% and 35% relative to baseline was achieved with BOL-303259-X at doses of 0.036% (9 µg) and 0.12% (36 µg), respectively. In comparison, latanoprost elicited a greater response than vehicle only at 0.1% (30 µg) with a peak effect of 26%. In glaucomatous dogs, IOP decreased from baseline by 44% and 10% following BOL-303259-X (0.036%) and vehicle, respectively. Latanoprost (0.030%) lowered IOP by 27% and vehicle by 9%. Intravitreal injection of hypertonic saline in rabbits increased IOP transiently. Latanoprost did not modulate this response, whereas BOL-303259-X (0.036%) significantly blunted the hypertensive phase. Following BOL-303259-X treatment, latanoprost acid was significantly elevated in rabbit and primate cornea, iris/ciliary body and aqueous humor as was cGMP in aqueous humor. BOL-303259-X lowered IOP more effectively than latanoprost presumably as a consequence of a contribution by NO in addition to its prostaglandin activity. The compound is now in clinical development for the treatment of glaucoma and ocular hypertension.

[Effect of acupuncture on the expression of Bcl-xl and BDNF of retina in rabbits with chronic intraocular hypertension].

OBJECTIVE: To explore the protection effects of acupuncture on glaucomatous optic nerve damage and its mechanism. METHODS: Experimental glaucoma model was induced by intracameral injection of compound Carbomer solution in rabbits. After 28 days, ocular tension returned to normal by filtration surgery. Twenty rabbits (40 eyes) were randomly divided into a model group, an acupuncture group, a neurotrophy group and a nomal control group, 5 cases in each group. The acupuncture group was treated with acupuncture at bilateral "Qiuhou" (EX-HN 7),"Fengchi" (GB 20) and "Xingjian" (LR 2), twice a day. The neurotrophy group was treated with intramuscular injection of Vitamin B1 (100 mg) and Vitamin B12 (500 microg), once a day, and the other groups with no treatment. The expressions of Bcl-xl and BDNF in rabbits retina were observed after 4 weeks. RESULTS: At the end of the experiment, the positive expression cells of Bcl-xl and BDNF were (31.20 +/- 5.97) per mm2 and (6.3 +/- 1.89) per mm2 in the acupuncture group, being significantly higer than (26.70 +/- 4.32) per mm2 and (4.0 +/- 1.89) per mm2 in the model group (both P<0.05). CONCLUSION: Acupuncture can raise the expression of Bcl-xl and BDNF of retina, so as to prevent optic nerve damage caused by intraocular hypertension.

Retinal oxidative stress induced by intraocular hypertension in rats may be ameliorated by brimonidine treatment and N-acetyl cysteine supplementation.

PURPOSE: To investigate the effect of brimonidine and N-acetyl cysteine (NAC) on retinal oxidative status under ocular hypertension. MATERIALS AND METHODS: Ocular hypertension is produced in right eyes of 60 rats through intraocular injection of sodium hyaluronate. The left eyes received intracameral saline as sham. Twenty right eyes (brimonidine group) received topical brimonidine twice a day for a week. Other 20 eyes received intraperitoneal NAC (NAC group) once a day. Another group of 20 eyes were followed without any drugs but only intracameral sodium hyaluronate (sodium hyaluronate group) into right eyes. RESULTS: Intraocular injection of sodium hyaluronate increased intraocular pressure for a week and caused retinal peroxidation and decreased glutathione peroxidase and catalase levels. Brimonidine and NAC treatment reversed the retinal oxidative stress created by high intraocular pressure. CONCLUSIONS: Brimonidine and NAC supplementation provide antioxidative properties to retina and decrease retinal damage induced by ocular hypertension.

Effect of topical Ginkgo biloba extract on steroid-induced changes in the trabecular meshwork and intraocular pressure.

OBJECTIVE: To study the effects of Ginkgo biloba extract (GBE) on dexamethasone (DEX)-induced ocular hypertension. METHODS: Rabbits aged 7 weeks received topical TobraDEX (Alcon Labs, Hünenberg, Switzerland) and/or 5 microg of GBE four times daily for 14 days. Intraocular pressure (IOP) was recorded every 3 days. After enucleation, trabecular meshwork (TM) cellularity and extracellular matrix deposition were graded. The effect of GBE on apoptosis and expression of myocilin and cell stress-related genes in DEX-treated human TM cells were studied by immunofluorescence, Western blotting, and quantitative polymerase chain reaction. RESULTS: Ginkgo biloba extract suppressed DEX-induced IOP elevation in rabbits. It reduced the DEX-associated accumulation of extracellular materials within the cribriform layers of the TM and achieved better TM cellularity. In cultured human TM cells, GBE substantially attenuated anti-Fas ligand-induced apoptosis and reduced DEX-induced myocilin expression. Ginkgo biloba extract modulated the expression of alphaB-crystallin and heat-shock proteins 70 and 90alpha but not other stress-related genes. Furthermore, changes associated with DEX were found less in GBE-treated or GBE-primed TM cells. CONCLUSION: We showed that GBE, a nontoxic, antiapoptotic, herbal compound significantly suppressed steroid-induced IOP elevation in rabbits and it seems to prevent the adverse effects of DEX on TM cells. CLINICAL RELEVANCE: Ginkgo biloba extract could be a therapeutic agent or dietary supplement to prevent steroid-induced ocular hypertension.

Agonists of the serotonin 5-HT2C receptor: preclinical and clinical progression in multiple diseases.

The serotonin 5-HT2C receptor is a G-protein-coupled receptor and is one of the 14 subtypes that constitutes the serotonin receptor family. Agonists of 5-HT2C have been implicated as potential treatments for diseases of significant unmet medical need, including obesity and schizophrenia. Despite approximately 10 years of discovery efforts, 5-HT2C agonists have only recently advanced into the clinic, likely because many of the early drug discovery efforts experienced significant difficulties with attaining receptor selectivity. Several of these issues related to receptor selectivity have now been overcome, resulting in the entry of compounds into advanced clinical trials. This review summarizes the progress in 5-HT2C agonist discovery and clinical development over the last 3 years. [sw1]what are the several issues - several issues relating to receptor selectivity?

[Hypothesis on the role of nutritional factors in ocular hypertension and glaucoma]. / Hypothèses sur le rôle des facteurs nutritionnels au cours des hypertonies oculaires et du glaucome.

Recent notions in connection with oxidative stress and the fat balance of long chain polyunsaturated fatty acids (PUFA) families have brought new insight to a probable role of nutritional factors in glaucoma and intraocular hypertony. The modifications of the extracellular matrix of the trabecula could be influenced by oxidative stress. On the one hand, collagen apoptosis and remodeling (associated with an increase in intraocular pressure) are mainly influenced by hydrosoluble antioxidants such as glutathione. On the other hand, elastin apoptosis and remodeling (correlated with the occurrence of optic atrophy) are particularly influenced by liposoluble antioxidants such as vitamin E. In addition, the dietary ratio of omega3/omega6PUFA intake could influence the balance of intraocular pressure. Omega-3 PUFA could influence cyclooxygenase competition. A diet with increased omega-3 and decreased omega-6 could thus favor an increase in intraocular pressure reducing synthesis of PG-F2, leading to a decrease in uveoscleral outflow. The true importance of these factors has not yet been solidly determined and studies are in progress to clarify the real implication of these nutritional factors.

Neurochemical correlates of cortical plasticity after unilateral elevated intraocular pressure in a primate model of glaucoma.

PURPOSE: To examine the time course of changes in the expression patterns of several synaptic plasticity markers in the primary visual cortex after unilateral elevated intraocular pressure (IOP) in a primate model of glaucoma. METHODS: A monkey model of experimental glaucoma was combined with immunohistochemical and histochemical methods to assess changes in expression patterns and metabolic activity of cortical neurons in V1. RESULTS: Experimental unilateral glaucoma altered the spatial and temporal distribution of several neurochemicals associated with cortical plasticity in V1 of the primate. Within-animal comparisons of immunohistochemical studies revealed that GABAa receptor protein and GAP-43 were significantly lower in glaucomatous versus normal eye bands after 2, 4, and 7 months of elevated IOP. SYN immunoreactivity was also lower in the glaucomatous versus the normal eye bands but only at 4 months of elevated IOP. CAMKIIalpha immunoreactivity levels were higher in the glaucomatous versus the normal eye bands. Between-animal comparisons revealed that the levels of GAP-43 and SYN were upregulated, whereas levels of GABAa receptor protein were downregulated, in glaucomatous eyes when compared with levels in the visual cortex of normal animals. CONCLUSIONS: Unilateral elevation of IOP affects both the metabolic activity of cortical neurons and the expressed levels of GAP-43, SYN, GABAa receptor protein, and CAMKIIalpha, as measured immunohistochemically in the primary visual cortex of adult monkeys. Because these neurochemicals are thought to be necessary for synaptic plasticity, their redistribution may support functional recovery of cortical neurons after damage to retinal ganglion cells induced by elevated IOP.

A randomized trial of the long-term effects of digital ocular compression in the late postoperative period.

PURPOSE: To determine whether digital ocular compression is a viable technique to lower intraocular pressure in patients at least 3 months after trabeculectomy. PATIENTS AND METHODS: A 6-month prospective, randomized, controlled, single-masked trial of 29 patients who underwent a trabeculectomy at the Glaucoma Service of Wills Eye Hospital. Patients were assigned to two groups: ocular compression or cheekbone compression (control group). The ocular compression group performed compression to the operated eye three times a day in the pattern of 10 seconds of pressure, 5 seconds of rest, and 10 seconds of pressure. Pressure was applied with the index finger through the closed lid to the center of the cornea. Pressure was steady and firm, but not painful. No massaging was performed. The cheekbone compression group applied pressure to the zygomatic arch with an identical style and frequency. RESULTS: At 6 months, the change in mean intraocular pressure for the ocular compression group was 0.25 mm Hg compared with -0.44 mm Hg for the control group (P = 0.7). A few patients in both groups experienced large swings in intraocular pressure and mild to moderate discomfort. CONCLUSION: Ocular compression had little to no success in the long-term management of increased intraocular pressure in the late postoperative period in this study.

Short-term effect of latanoprost and timolol eye drops on tear fluid and the ocular surface in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE: To investigate and compare the short term effects of topical latanoprost and timolol on the tear fluid and ocular surface condition in patients with bilateral primary open angle glaucoma or ocular hypertension. METHODS: Thirty-seven patients were included in this randomized, double-masked, parallel group study. Patients received either latanoprost 0.005% (n= 18) or timolol 0.5% (n= 19) instilled once daily in the morning for a treatment period of 27 days. Routine ophthalmic examinations, including intraocular pressure measurement, as well as tests to evaluate tear fluid and the ocular surface were performed. RESULTS: After one drop of medication, tear secretion was significantly reduced by timolol, but not by latanoprost. At the end of the study the break-up time (BUT) was significantly decreased in the timolol group but not in the latanoprost group. The BUT still remained in the normal range in both groups, although it is important to note that timolol was administered at half the clinical dose. Both latanoprost and timolol tended to increase Rose-Bengal staining of the cornea and conjunctiva after one month of treatment but no statistically significant difference was found between the groups. Corneal sensitivity was within the normal range for all patients during the study. CONCLUSION: Regarding ocular surface effects, no clinically important differences between latanoprost and timolol were observed as all the effects remained in the normal range.

[Protective effects of exogenous superoxide dismutase on rabbit retinal injury by acute intraocular hypertension].

OBJECTIVE: To study active oxygen and free radical injury in rabbit retina during elevated intraocular pressure and the protective effect of exogenous superoxide dismutase (SOD) on the retinal damage by the hypertension. METHODS: Lipid peroxidative product, malondialdehyde (MDA), activity of SOD and glutathione peroxidase (GSH-Px), reduced GSH in the retinal tissue were measured during 24 h after the release of an ocular hypertension, 6.67 kPa (1 kPa = 7.5 mmHg) maintaining for 1.5 h, and the effects of retrobulbarly injected Cu-Zn-SOD on the level of MDA and the activity of SOD in the retinal tissue after the release of ocular hypertension for 12 h were observed. RESULTS: MDA increased gradually during 0-12 h after the release of ocular hypertension and maintained at a relatively high level in 12-24 h. The activity of SOD and GSH-Px was lower than normal level immediately after the release, and then increased to a certain different extent. But the activity of SOD began to decrease gradually 4 h after the release. GSH had no significant changes during 24 h after the release. Retrobulbar injection of Cu-Zn-SOD reduced the production of MDA in the retinal tissue and enhanced SOD activity. CONCLUSIONS: Active oxygen and free radicals participate the rabbit retinal injury by elevated intraocular pressure. A high dose of Cu-Zn-SOD retrobulbar injection plays a beneficial role in enhancing the antioxidative ability of the retina.