Biomedical subjects

Masaaki Tokuda

Publications and source records attributed to Masaaki Tokuda.

At least 19 recordsLinked to original sources

PubMed2007

p90 RSK-1 associates with and inhibits neuronal nitric oxide synthase.

Evidence is presented that RSK1 (ribosomal S6 kinase 1), a downstream target of MAPK (mitogen-activated protein kinase), directly phosphorylates nNOS (neuronal nitric oxide synthase) on Ser847 in response to mitogens. The phosphorylation thus increases greatly following EGF (epidermal growth factor) treatment of rat pituitary tumour GH3 cells and is reduced by exposure to the MEK (MAPK/extracellular-signal-regulated kinase kinase) inhibitor PD98059. Furthermore, it is significantly enhanced by expression of wild-type RSK1 and antagonized by kinase-inactive RSK1 or specific reduction of endogenous RSK1. EGF treatment of HEK-293 (human embryonic kidney) cells, expressing RSK1 and nNOS, led to inhibition of NOS enzyme activity, associated with an increase in phosphorylation of nNOS at Ser847, as is also the case in an in vitro assay. In addition, these phenomena were significantly blocked by treatment with the RSK inhibitor Ro31-8220. Cells expressing mutant nNOS (S847A) proved resistant to phosphorylation and decrease of NOS activity. Within minutes of adding EGF to transfected cells, RSK1 associated with nNOS and subsequently dissociated following more prolonged agonist stimulation. EGF-induced formation of the nNOS-RSK1 complex was significantly decreased by PD98059 treatment. Treatment with EGF further revealed phosphorylation of nNOS on Ser847 in rat hippocampal neurons and cerebellar granule cells. This EGF-induced phosphorylation was partially blocked by PD98059 and Ro31-8220. Together, these data provide substantial evidence that RSK1 associates with and phosphorylates nNOS on Ser847 following mitogen stimulation and suggest a novel role for RSK1 in the regulation of nitric oxide function in brain.

Amino Acid Sequence↗

PubMed2006

Activation of the JAK-STAT signaling pathway in the rat basilar artery after subarachnoid hemorrhage.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) is one of the most important signaling pathways transducing signals from the cell surface in response to cytokines. Subarachnoid hemorrhage (SAH) produces cytokines in the CSF. We investigated whether this signaling pathway is activated in the rat basilar artery after SAH by cytokines. In a rat single-hemorrhage model of SAH, basilar arteries and CSF were obtained until 7 days after SAH. The concentration of interleukin-6 (IL-6) in CSF was measured by ELISA. Western blot analysis with JAK1, phosphospecific-JAK1, STAT3, phosphospecific STAT3 at Tyr705 and Ser727, cyclooxygenase-2 (COX-2), and actin antibodies was performed in basilar artery. The expressions of STAT3, phosphospecific STAT3 at Tyr705 and Ser727, and COX-2 in basilar artery were examined by immunohistochemical studies. The concentration of IL-6 immediately increased after SAH and Western blot analysis revealed that JAK1 was phosphorylated within 2 h, accompanied by phosphorylation of STAT3 at Tyr705, extending to Ser727 at days 1-2. Immunohistochemistry revealed phosphorylation of STAT3 to occur in endothelial and smooth muscle cells of the basilar artery. In addition, intracisternal injection of IL-6 by itself significantly increased phosphorylation of STAT3 at Tyr705 and Ser727. Expression of COX-2 was also upregulated in endothelial cells of the basilar artery. These results indicate that SAH produces the proinflammatory cytokine IL-6 in the CSF, which activates the JAK-STAT signaling pathway in the basilar artery and induces transcription of immediate early genes.

Animals↗

PubMed2006

Neuroprotective effects of D-allose against retinal ischemia-reperfusion injury.

PURPOSE: To investigate the effect of D-allose, a rare sugar, against ischemia reperfusion injury in the rat retina. METHODS: Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg and maintaining that level for 45 minutes. Morphometric studies were performed to study the effect of D-allose on the histologic changes induced by ischemia in the rat retina. Glutamate release from the rat retina and intravitreal P(O2) profiles were monitored during and after ischemia with a microdialysis biosensor and oxygen-sensitive microelectrodes. The release of hydrogen peroxide stained with diaminobenzidine hydrochloride was monitored by an in vitro retinal ischemia model. RESULTS: Seven days after the ischemia, significant reductions in both the number of ganglion cells and the thickness of the inner plexiform layer were observed. Pretreatment with D-allose significantly inhibited the ischemic injury of the inner retina. A large release of glutamate occurred during the ischemia. After the recirculation, glutamate levels were increased again and reached a maximum in approximately 20 minutes. The increases in extracellular glutamate during and after ischemia tend to be suppressed by administration of d-allose. d-Allose attenuated the increase in intravitreal P(O2) during reperfusion. After the ischemia, production of hydrogen peroxide was detected within approximately 30 minutes. D-allose suppressed the production of hydrogen peroxide. CONCLUSIONS: These results suggest that D-allose may protect neurons by decreasing extracellular glutamate and attenuating oxidative stress in ischemic insult.

Animals↗

PubMed2006

Improved microcirculatory effect of D-allose on hepatic ischemia reperfusion following partial hepatectomy in cirrhotic rat liver.

D-allose, one of the rare sugars produced from D-psicose, has been shown to be effective against reperfusion injury after ischemia and partial hepatectomy in cirrhotic rat liver by improving remnant liver blood flow and survival rates, and decreasing liver enzyme levels and liver tissue injury levels. These findings demand further study of the clinical implications of this sugar in view to the advancing fields of liver surgery and transplantation.

Animals↗

PubMed2006

Clinical significance of Skp2 expression, alone and combined with Jab1 and p27 in epithelial ovarian tumors.

We have previously demonstrated the inverse correlation of Jab1 and p27 proteins, as well as prognostic significance in epithelial ovarian carcinomas. In order to investigate Skp2 protein and its correlation with Jab1, p27, and clinical outcome, we evaluated Skp2 expression in a group of epithelial ovarian tumors. Immunohistochemical analysis was performed on 80 cases of ovarian tumors (33 benign and 47 malignant), and 26 of the 80 cases were evaluated by Western blot analysis. Immunofluorescence was carried out in the human ovarian adenocarcinoma cell line OVCAR-3. Skp2 expression was detected in 53.2% of malignant tumors and 18.2% of benign tumors. The positive ratio of Skp2 expression was increased from benign to malignant ovarian tumors (p=0.002). A negative correlation between Skp2 and p27 was found in benign and malignant ovarian tumors (p=0.006 and p<0.0001, respectively). Skp2 expression was significantly associated with high tumor grade (p=0.001), lymph node metastasis (p=0.01), and residual disease (p=0.012). Kaplan-Meier survival analysis showed that Skp2 expression was significantly associated with poor prognosis (p=0.013), and patients with Skp2(+)/Jab1(+)p27(-) expression had the worst prognosis among all phenotypes of Skp2/Jab1/p27 expression (p=0.0007). Our results suggest that Skp2 expression was significantly associated with malignancy, and the Skp2 protein level may be a valuable prognostic factor for epithelial ovarian carcinomas. Furthermore, the combined evaluation of Skp2/Jab1/p27 proteins provides important prognostic information on patients with epithelial ovarian carcinoma.

Blotting, Western↗

PubMed2006

Alteration and clinical relevance of PTEN expression and its correlation with survivin expression in epithelial ovarian tumors.

The tumor suppressor PTEN, phosphatase and tensin homolog on chromosome 10, plays an essential role in regulating signaling pathways involved in cell growth and apoptosis and is inactivated in a wide variety of tumors. Survivin, a member of the inhibitor of apoptosis protein family (IAP), is associated with cell proliferation, and overexpressed in common human tumors. Both PTEN and survivin proteins can regulate cell cycle and apoptosis, but their biological effects are adverse. We have previously investigated the role of survivin expression in epithelial ovarian tumors. In this study, we evaluated the alteration and clinical relevance of PTEN expression and further assessed its correlation with survivin expression in epithelial ovarian tumors. Immunohistochemical analysis was performed in 103 cases of ovarian tumors, and 26 of the 103 cases were evaluated by Western blot analysis. PTEN expression was reduced from benign to malignant ovarian tumors (p=0.0003), and an inverse correlation between PTEN and survivin was found in benign, borderline, and malignant tumors (p=0.004, p=0.015 and p=0.0005, respectively). PTEN expression was significantly associated with tumor grade (p=0.001), histological subtype (p=0.037), ascites (p=0.038), and residual disease (p=0.0006). Kaplan-Meier survival analysis showed that the loss of PTEN expression was significantly associated with poor overall survival (p=0.021), and patients with PTEN(-)/survivin(+) expression had the worst prognosis among all phenotypes of PTEN/survivin expression (p=0.039). Our results suggest that the altered PTEN expression and its inverse correlation with survivin may be involved in the development and progression of ovarian tumors, and the combined detection of PTEN and survivin proteins might be more valuable in the evaluation of malignancy and prognosis in epithelial ovarian tumors.

Epithelial Cells↗

PubMed2005

Inhibition of neuronal nitric-oxide synthase by phosphorylation at Threonine1296 in NG108-15 neuronal cells.

We demonstrate that neuronal nitric-oxide synthase (nNOS) is directly inhibited through the phosphorylation of Thr(1296) in NG108-15 neuronal cells. Treatment of NG108-15 cells expressing nNOS with calyculin A, an inhibitor of protein phosphatase 1 and 2A, revealed a dose-dependent inhibition of nNOS enzyme activity with concomitant phosphorylation of Thr(1296) residue. Cells expressing a phosphorylation-deficient mutant in which Thr(1296) was changed to Ala proved resistant to phosphorylation and suppression of NOS activity. Mimicking phosphorylation mutant of nNOS in which Thr(1296) is changed to Asp showed a significant decrease in nNOS enzyme activity, being competitive with NADPH, relative to the wild-type enzyme. These data suggest that phosphorylation of nNOS at Thr(1296) may involve the attenuation of nitric oxide production in neuronal cells through the decrease of NADPH-binding to the enzyme.

Animals↗

PubMed2005

Prognostic significance of Jab1 expression in laryngeal squamous cell carcinomas.

PURPOSE: Jun activation domain-binding protein 1 (Jab1) is known as a coactivator of AP1 transcription factor, which contributes to tumor progression by degrading the p27kip1 protein. The purpose of this study is to investigate whether Jab1 expression is correlated with p27kip1 level and cell proliferation, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of laryngeal squamous cell carcinoma (LSCC). EXPERIMENTAL DESIGN: Immunohistochemical and/or Western blot analysis was done in HEp-2 cells and 102 cases of LSCCs. RESULTS: Jab1 expression was negatively associated with p27kip1 expression and was positively associated with cell proliferation both in HEp-2 cells and LSCCs. Jab1 overexpression was detected in 51% LSCCs and was significantly associated with unfavorable clinicopathologic variables. Survival analysis revealed that Jab1 overexpression is significantly associated with short disease-free and overall survival (P = 0.0036 and P = 0.0001, respectively). When Jab1 and p27kip1 are combined, patients with Jab1(+)/p27kip1(-) revealed poor disease-free and overall survival (P= 0.0008 and P < 0.0001, respectively). When Jab1 expression and lymph node status are combined, patients with Jab1(+)/lymph node(+) revealed poorer disease-free andoverall survival than others (P < 0.0001 and P < 0.0001, respectively). Furthermore, patients with the phenotype of Jab1(+)/p27kip1(-)/lymph node(+) revealed the worst disease-free and overall survival (P < 0.0001 and P < 0.0001, respectively). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival. CONCLUSIONS: These findings suggested that Jab1 protein may contribute to the tumor progression and represent a novel prognostic indicator for LSCCs.

Adult↗

PubMed2005

D-allose, an all-cis aldo-hexose, suppresses development of salt-induced hypertension in Dahl rats.

OBJECTIVE: D-allose, an all-cis aldo-hexose, is non-caloric and possesses antioxidant properties. We investigated the effects of oral D-allose supplementation on the development of high blood pressure and the oxidative status in two genetically hypertensive animal models: Dahl salt-sensitive hypertensive (DS) rats and spontaneously hypertensive rats. METHODS AND RESULTS: The systolic blood pressure of DS rats fed a 4% salt diet for 4 weeks significantly increased from 122+/-8 to 161+/-5 mmHg as compared with DS rats fed a normal salt diet (138+/-5 mmHg at 4 weeks), whereas concordant supplementation of D-allose, but not D-glucose, with a dose of 2 g/kg daily to salt-loaded DS rats suppressed the development of high blood pressure (135+/-7 mmHg at 4 weeks), accompanied with decreases in superoxide production in the aorta that was determined by the lucigenin chemiluminescence and dihydroethidium staining. The increases of urinary protein secretion of salt-loaded DS rats were prevented by D-allose supplementation (DS rats fed 0.5% salt, 18.2+/-6.3 mg/day; DS rats fed 4% salt alone, 81.8+/-16.5 mg/day; DS rats fed 4% salt+D-allose, 31.3+/-11.8 mg/day; DS rats fed 4% salt+D-glucose, 85.3+/-20.5 mg/day). On the other hand, D-allose supplementation in spontaneously hypertensive rats had no significant effect on the blood pressure or the aortic superoxide production during the early developing stage of hypertension. CONCLUSIONS: These results underscore the role of enhanced oxidative stress in the pathogenesis of high blood pressure development in DS rats, and suggest the possibility of D-allose supplementation for prevention of salt-sensitive hypertension.

Animals↗

PubMed2005

Neuroprotective effect of D-psicose on 6-hydroxydopamine-induced apoptosis in rat pheochromocytoma (PC12) cells.

We evaluated the neuroprotective effects of D-psicose, one of the rare sugars, on 6-hydroxydopamine (6-OHDA)-induced apoptosis in catecholaminergic PC12 cells, the in vitro model of Parkinson's disease (PD). Apoptotic characteristics of PC12 cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. The results showed that D-psicose at a concentration of 50 mM, exerted significant protective effects against the 6-OHDA (200 muM)-induced PC12 cell apoptosis, while other sugars had little or no protective effects. We have observed a significant increase in the level of intracellular glutathione after 24 h in 6-OHDA (200 muM) treated cells, while a decrease in the level was observed at 3 h and 6 h. Also, a synergistic exposure to D-psicose and 6-OHDA for 24 h showed a significant increase in intracellular glutathione level. Therefore, these results suggest that D-psicose may play a potential role as a neuroprotective agent in the treatment of neurodegenerative diseases by inducing an up-regulation of intracellular glutathione.

Adrenergic Agents↗

PubMed2005

Comparison study of the expressions of myristoylated alanine-rich C kinase substrate in hepatocellular carcinoma, liver cirrhosis, chronic hepatitis, and normal liver.

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells. The aim of this study was not only to evaluate the expression and localization of MARCKS in various pathological liver tissues, including HCC, but also to analyze the difference in MARCKS expression between hepatitis virus-induced HCC and cirrhosis. The level of MARCKS and its phosphorylated proteins, as well as its localization, were determined using Western blot and/or immunohistochemistry in HCC and other pathological liver tissues. We also analyzed the change of MARCKS localization on the influence of MARCKS phosphorylation in the HLF cancer cell line by phosphorylation study. In addition, the relationship between MARCKS expression and proliferative activity was studied in HCC. In the immunohistochemical study, a very small amount of MARCKS protein was found along the contour of the hepatocellular membrane in normal liver and in cases of chronic hepatitis. MARCKS was up-regulated in liver cirrhosis tissue and was localized in the cytoplasm of hepatocytes. The expression of MARCKS was down-regulated in HCC tissues, as compared with non-tumorous liver cirrhosis tissues from the same patients. Furthermore, MARCKS was serine-phosphorylated in liver cirrhosis and HCC, and phosphorylated MARCKS was detected in a cytosolic fraction of these tissues. In a phosphorylation study using the HLF HCC cell line, MARCKS was displaced from the plasma membrane to the cytosol following the activation of protein kinase C (PKC) by phorbol 12-myristrate 13-acetate (PMA). Furthermore, the activity of cyclin D1 and cyclin E kinases was found to be higher in HCCs with low MARCKS expression than in HCCs with high MARCKS expression. These results suggest that up-regulation of MARCKS might be essential in the generation of cirrhotic nodules through chronic hepatitis from normal liver, and that the phosphorylation and/or down-regulation of MARCKS might play an important role in the development and progression of HCC from liver cirrhosis.

Adult↗

PubMed2005

The inhibitory effect and possible mechanisms of D-allose on cancer cell proliferation.

Rare sugars are monosaccharides distributed rarely in nature, because of its very limited amount and cost, the biological effect has hardly been studied. Recently, an effective strategy for mass production of rare sugars has been developed. As a result, a wide range of study of rare sugars from the basic to applied research has become possible. For biological application of rare sugars, it is necessary to fundamentally investigate the relationships between rare sugars and living cells in terms of physiology. Therefore, we firstly examined the effect of rare sugars including D-psicose, D-allose, D-altrose and D-talitol on cell proliferation using certain cell lines in vitro. Cell growth was evaluated by MTT assay after 24-, 48- and 72-h treatment. The result shows that D-allose has a significant inhibitory effect on cancer cell proliferation in a dose-dependent manner. Although the exact mechanism remains unclear, this finding represents a novel aspect of the biological profile of D-allose and suggests that D-allose may be an effective adjuvant therapeutic agent against cancer in the future.

Apoptosis↗

PubMed2004

Modification of endothelial NO synthase through protein phosphorylation after forebrain cerebral ischemia/reperfusion.

BACKGROUND AND PURPOSE: Production of NO by endothelial NO synthase (eNOS) is thought to play a neuroprotective role after cerebral ischemia. The vascular endothelial growth factor (VEGF) contributes to activation of eNOS by Ca2+/calmodulin and also stimulates the protein kinase Akt, which directly phosphorylates eNOS on Ser1177 and increases enzyme activity. Although the expression of VEGF has been studied in ischemic stroke models, the activation of eNOS after cerebral ischemia has not been investigated. The purpose of the present study was to clarify molecular mechanisms underlying the regulation of eNOS activity through protein phosphorylation in postischemic processes. METHODS: Sprague-Dawley rats were subjected to forebrain cerebral ischemia for 15 minutes with hypotension and reperfusion for up to 24 hours. Western blot analysis and ELISAs were used to study the temporal profiles of Akt, phospho-Akt at Ser437, eNOS, phospho-eNOS at Ser1177, and VEGF expression, respectively. Immunohistochemical studies were performed to examine the spatial expression patterns of phospho-Akt at Ser437 and phospho-eNOS at Ser1177. RESULTS: Increase in phospho-Akt at Ser437 was observed transiently 0.5 to 2 hours after reperfusion, whereas elevation of phospho-eNOS at Ser1177 and VEGF expression was observed from 6 hours after reperfusion. Endothelial cells in the microvessels were the major source of eNOS phosphorylated at Ser1177 at the 12-hour time point. CONCLUSIONS: Increase in Ser1177 phospho-eNOS occurs in endothelial cells of microvessels after ischemic episodes with temporal expression of VEGF, pointing to a contribution to the autoregulation of postischemic brain damage.

Animals↗

PubMed2004

Calcium/calmodulin-dependent protein kinase I inhibits neuronal nitric-oxide synthase activity through serine 741 phosphorylation.

We demonstrate here that neuronal nitric-oxide synthase (nNOS) is phosphorylated and inhibited by a constitutively active form of Ca2+/calmodulin (CaM)-dependent protein kinase I (CaM-K I1-293). Substitution of Ser741 to Ala in nNOS blocked the phosphorylation and the inhibitory effect. Mimicking phosphorylation at Ser741 by Ser to Asp mutation resulted in decreased binding of and activation by CaM, since the mutation was within the CaM-binding domain. CaM-K I1-293 gave phosphorylation of nNOS at Ser741 in transfected cells, resulting in 60-70% inhibition of nNOS activity. Wild-type CaM-K I also did phosphorylate nNOS at Ser741 in transfected cells, but either CaM-K II or CaM-K IV did not. These results raise the possibility of a novel cross-talk between nNOS and CaM-K I through the phosphorylation of Ser741 on nNOS.

Alanine↗

PubMed2004

Phosphohippolin expression in the rat central nervous system.

The FXYD family is a small single-span membrane protein family; recently, we have identified a novel member of this family from the cDNA library of the rat hippocampus and named phosphohippolin (Php) (Mol. Br. Res. vol. 86, 2001). The deduced amino acid sequence of this novel Php comprises 93 residues with a core motif of FXYD and a single transmembrane domain. This indicates that Php belongs to FXYD6 subfamily of the seven FXYD subfamilies (FXYD1-7). Php shows a 48.1% homology with rat phospholemman (FXYD1), a transmembrane family protein. In this study, polyclonal antibodies against the carboxyl-terminal sequence of rat Php were raised and purified. The spatial expression of the Php protein was in the neuronal fibers of the medial part of lateral habenula nucleus, thalamus, hypothalamus, stria terminalis, zona incerta, amygdaloid body and cingulum, olfactory bulb, hippocampus, cerebral cortex and cerebellum. A unique Php distribution was identified in the cerebellum, with a predominant expression pattern in the granule layer of lobules VI-IX of the posterior lobe. Developmental studies demonstrated that the highest level of Php expression was seen in the postnatal (PN) 3-week-old rat brain, and a significant amount of Php still existed in the adult brain. These findings suggest that Php may play an important role in the excitability of neurons in the central nervous system during postnatal development, as well as those in the adult brain.

Aging↗

PubMed2004

D-Allose has a strong suppressive effect against ischemia/reperfusion injury: a comparative study with allopurinol and superoxide dismutase.

BACKGROUND/PURPOSE: D-Allose, a rare sugar, is one of the potent inhibitors of ischemia/reperfusion injury of the rat liver. To investigate the potency of this powerful agent we examined its effect against ischemia/reperfusion injury and compared it to that of allopurinol and superoxide dismutase. METHODS: Male Lewis rats were given water ad libitum preoperatively for 12 h and anesthetized by isoflurane inhalation anesthesia. Drugs were administered through a polyethylene catheter inserted into the portal vein for 2 h (D-allose), 10 min (allopurinol), or 5 min (superoxide dismutase) before ischemia, and the livers were then subjected to 70% ischemia, induced by crossclamping the vessels to the lateral and median lobes of the liver for 90 min. Rats were divided into four groups: group 1, pretreated with vehicle (normal saline); group 2, treated with D-allose; group 3, treated with allopurinol; and group 4, treated with superoxide dismutase. The effects of the drugs were evaluated by liver hemodynamics, neutrophil count, myeloperoxidase, liver enzymes, and histological studies. RESULTS: D-Allose improved liver hemodynamics (P < 0.001) and postischemic animal survival (P < 0.05) significantly compared with the control group and nonsignificantly compared with the allopurinol and superoxide dismutase groups. Myeloperoxidase activity in the postischemic liver tissue was decreased significantly (P < 0.05) by D-allose compared with all other treatment and control groups. Neutrophil count was also significantly (P < 0.05) decreased in the D-allose group compared with than that in the control group, as well as the superoxide dismutase group. Only D-allose produced a statistically significant decrease in the level of liver enzymes, compared with levels in the control group. CONCLUSIONS: The moderately protective effect of D-allose, which caused no clinical side effects, is encouraging. D-Allose had the best protective effect against neutrophil-related postischemic injury of the liver tissue, followed by allopurinol and superoxide dismutase. However, a more extensive study is needed to ensure the effects as well as the mechanisms of the effect of this rare sugar.

Allopurinol↗

PubMed2004

Izumoring: a novel and complete strategy for bioproduction of rare sugars.

Starch, whey or hemicellulosic waste can be used as a raw material for the industrial production of rare sugars. D-glucose from starch, whey and hemicellulose, D-galactose from whey, and D-xylose from hemicellulose are the main starting monosaccharides for production of rare sugars. We can produce all monosaccharides; tetroses, pentoses and hexoses, from these raw materials. This is achieved by using D-tagatose 3-epimerase, aldose isomerase, aldose reductase, and oxidoreductase enzymes or whole cells as biocatalysts. Bioproduction strategies for all rare sugars are illustrated using ring form structures given the name Izumoring.

Journal Article↗

PubMed2004

The Ginkgo biloba extract (EGb 761) provides a neuroprotective effect on retinal ganglion cells in a rat model of chronic glaucoma.

PURPOSE: To investigate the effect of Ginkgo biloba extract (EGb 761) against neurotoxicity of retinal ganglion cells of rats with chronic moderately elevated intraocular pressure (IOP). METHODS: Unilateral chronic moderately elevated IOP was produced in rats by cautery of three episcleral vessels. Secondary degeneration was measured with and without EGb 761 for 5 months. At 5 months, retinal ganglion cells were labeled with a fast blue tracer applied to both superior colliculi. Densities of surviving retinal ganglion cells were estimated by counting fast blue labeled cells in whole mounted retinas. RESULTS: When compared with their contralateral control eyes with normal IOP, in the peripheral retina, retinal ganglion cell loss in eyes with chronic, moderately elevated IOP was 29.8 +/- 1.5% (n=5) at 5 months in untreated animals and 4.6 +/- 4.5% (n=5) at 5 months in treated animals with EGb 761. CONCLUSIONS: Pretreatment and early posttreatment with EGb 761 is an effective neuroprotectant in a rat model of chronic glaucoma.

Animals↗