Biomedical subjects

Hideaki Hara

Publications and source records attributed to Hideaki Hara.

At least 19 recordsLinked to original sources

PubMed2006

Intravitreal injection of endothelin-1 caused optic nerve damage following to ocular hypoperfusion in rabbits.

The purpose of this study was to investigate the time course of the ocular hypoperfusion, retinal damage, and optic nerve damage induced by intravitreal injection of endothelin-1 (ET-1) in rabbits. ET-1, at 5 pmol (20 microL, twice a week for 2 or 4 weeks), was injected from the pars plana into the posterior vitreous of the right eye. Optic nerve head (ONH) blood flow and retinal artery diameter, together with the neurofilament light chain (NF-L) content, retinal morphology, and axon density of the optic nerve, were evaluated at 2, 4, and 8 weeks after the first injection of ET-1 (n=7 or 8). Tissue blood velocity in ONH was measured using a laser speckle method, and the diameter of major retinal arteries on the rim of the ONH was calculated from fundus photographs by a masked observer. Histological analysis and immunoblot evaluation of NF-L in the optic nerve were performed to evaluate optic nerve damage. At 2 weeks after the first ET-1 injection, tissue blood velocity was decreased by approximately 20% (versus the contralateral eye), and the diameter of retinal arteries had decreased by approximately 40%. These changes were sustained at the same level until 8 weeks after the first ET-1 injection. At 4 and 8 weeks after the first ET-1 injection, the amount of NF-L in the optic nerve was significantly less in the ET-1 treated eyes than in the contralateral eyes. At 8 weeks after the first ET-1 injection, a loss of myelinated axons and increases in gliosis and connective tissue were noted in the optic nerve of the treated eye, and the optic nerve-axon number had decreased significantly (each, versus the untreated eye). Retinal ganglion cells in the retina were not observed any damage at 2, 4, and 8 weeks after ET-1 injection. In conclusion, intravitreal injection of ET-1 induced chronic hypoperfusion in the ONH and retina, which presumably caused decreases in NF-L content and axon number in the optic nerve noted in the later part of the observation period.

Animals↗

PubMed2006

Glucocorticoid modulatory element-binding protein 1 binds to initiator procaspases and inhibits ischemia-induced apoptosis and neuronal injury.

Caspases are divided into two classes: initiator caspases, which include caspase-8 and -9 and possess long prodomains, and effector caspases, which include caspase-3 and -7 and possess short prodomains. Recently, we demonstrated that glucocorticoid modulatory element-binding protein 1 (GMEB1) interacts with the prodomain of procaspase-2, thereby disrupting its autoactivation and the induction of apoptosis. Here we show that GMEB1 is also capable of binding to procaspase-8 and -9. GMEB1 attenuated the Fas-mediated activation of these caspases and the subsequent apoptosis. The knockdown of endogenous GMEB1 using RNA interference revealed that cells with decreased GMEB1 expression are more sensitive to stress and undergo accelerated apoptosis. Transgenic mice expressing a neurospecific GMEB1 had smaller cerebral infarcts and less brain swelling than wild-type mice in response to transient focal ischemia. These results suggest that GMEB1 is an endogenous regulator that selectively binds to initiator procaspases and inhibits caspase-induced apoptosis.

Animals↗

PubMed2006

Morphometric evaluation of changes with time in optic disc structure and thickness of retinal nerve fibre layer in chronic ocular hypertensive monkeys.

We examined the time course of changes in optic disc structure by means of a scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT) in ocular hypertensive (experimental glaucoma) monkeys, and clarified the relationships between the histological RNFL thickness and HRT parameters. Further, the time course of changes in retinal nerve fiber layer (RNFL) thickness in individual eyes was measured using a scanning laser polarimeter with fixed corneal polarization compensator (GDx FCC). In the present study, two separate experiments were carried out. A chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eye in 11 cynomolgus monkeys. In Experiment 1, the HRT and GDx parameters were measured 12 weeks after the laser treatment in 10 eyes in five monkeys. In Experiment 2, the time course of changes in the HRT and GDx parameters was examined before and 1, 3, 4, 5, 6, 8, 10, 12, 14, and 16 weeks after the laser treatment in 12 eyes in six monkeys. The retardation values (thickness parameters) obtained from the GDx were used to derive thickness and ratio parameters in the superior, inferior, nasal and temporal quadrants. Ratio parameters were expressed as a ratio of superior and inferior quadrant to nasal quadrant. After the last measurements, each eye was enucleated, and retinal cross sections were prepared for histological analysis. In the left (hypertensive) eyes, IOP was persistently elevated throughout the observation periods in both Experiments 1 and 2. In the HRT measurements in Experiment 1, seven out of eight global topographic parameters (exception, disc area) were statistically different between the hypertensive and control eyes 12 weeks after the laser treatment. In Experiment 2, the HRT parameters changed in a time-dependent manner, but each of them almost plateaued at about 4 weeks after the laser treatment. Significant correlations were seen between the histological mean RNFL thickness at 1.5 disc diameters from the optic disc margin and the HRT parameters in 21 eyes from 11 monkeys in Experiments 1 and 2. Especially good correlations with histological mean RNFL thickness were seen for the rim volume and cup volume. In Experiment 1, good correlations were found between GDx ratio parameters and histological RNFL thickness in individual right control eyes (n=5). In individual left experimental glaucoma eyes of Experiment 2 (n=6), GDx ratio parameters declined in a time-dependent manner alongside the IOP elevation. In conclusion, alongside the IOP elevation, time-related changes in optic disc topography and RNFL thickness were demonstrated in monkey eyes using HRT and GDx. HRT (rim and cup) parameters showed good correlations with histological RNFL thickness, and significant interrelations.

Animals↗

PubMed2006

Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice.

Cerebral ischemia induces the expression of several growth factors and cytokines, which protect neurons against ischemic insults. Recent studies showed that granulocyte colony-stimulating factor (G-CSF) has a neuroprotective effect through the signaling pathway for the antiapoptotic cascade. The current study was designed to assess the neuroprotective mechanisms of G-CSF in ischemia/reperfusion injury using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). Mice were subjected to ischemia/reperfusion and divided into two groups: those treated with G-CSF (G-CSF group) and vehicle (control group) (n = 35 in each group). Immunohistochemistry and immunoblotting for antiapoptotic protein, nitrotyrosine, and inducible nitrate oxide synthase (iNOS) were performed. G-CSF significantly reduced stroke volume (34%, P < 0.006). G-CSF upregulated Stat3, pStat3, and Bcl-2 (P < 0.05), and suppressed iNOS and nitrotyrosine expression. In EGFP chimera mice, G-CSF decreased the migration of Iba-1/EGFP-positive bone marrow-derived monocytes/macrophages and increased intrinsic microglia/macrophages at ischemic penumbra (P < 0.05), suggesting that bone marrow-derived monocytes/macrophages are not involved in G-CSF-induced reduction of ischemic injury size. Our study indicated that G-CSF exerts a neuroprotective effect through the direct activation of antiapoptotic pathway, and suggested that G-CSF is important for expansion of the therapeutic time window in patients with cerebral ischemia.

Animals↗

PubMed2006

Brazilian green propolis protects against retinal damage in vitro and in vivo.

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retina in vitro and/or in vivo. In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin-reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In mice in vivo, propolis (100 mg kg(-1); intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitreal in vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage both in vitro and in vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

Journal Article↗

PubMed2006

Endothelin-1 impairs retrograde axonal transport and leads to axonal injury in rat optic nerve.

The purpose of this study was to examine the effects of endothelin-1 (ET-1) on retrograde axonal transport in the rat optic nerve. Vehicle or ET-1 (0.2, 1, or 5 pmol/eye) were injected into the vitreous body in Sprague-Dawley rats. Retinal vessels were observed, using a fundus camera, before, and at 10 min, 3 days and 7 days after a single intravitreous injection. Two days after the injection, a neuronal tracer, fluoro gold, was administered via the superior colliculi to retrogradely label active retinal ganglion cells (RGCs). Five days after the tracer administration, retrogradely labeled RGCs were evaluated in the flat-mounted retina, and cross sections from each optic nerve were graded for injury by four independent, masked observers. ET-1 at 5 pmol/eye caused a significant constriction of retinal vessels (versus the vehicle-treated group) at 10 min after the injection. Intravitreous injection of ET-1 caused a dose-related decrease in the number of retrogradely labeled RGCs. Injection of 5 pmol/eye ET-1 led to a statistically significant decrease in the number of retrogradely labeled RGCs (versus the vehicle-treated group). ET-1 at 1 and 5 pmol/eye caused histological optic nerve damage (evaluated using a graded scale). The histological optic nerve damage correlated with the number of retrogradely labeled RGCs. In conclusion, a single intravitreous injection of ET-1 impaired retrograde axonal transport in the rat optic nerve and this impairment correlated with the histological optic nerve damage.

Animals↗

PubMed2005

Sulfatides, L- and P-selectin ligands, exacerbate the intimal hyperplasia occurring after endothelial injury.

Leukocytes may be important in the development of intimal hyperplasia, but little is known about the participation of sulfatides (3-sulfated galactosyl ceramides) which are native ligands of L- and P-selectin. This study was designed to determine whether sulfatides affect the development of intimal hyperplasia. ICR mice were randomized to receive vehicle or sulfatides intravenously either at 1, 3, or 10 mg/kg/day for 7 days, or at 10 mg/kg/day for 1, 3, or 7 days. Endothelial damage was inflicted on the femoral artery via the photochemical reaction between rose bengal and green light. Scanning electron and light microscopic observations 3 days after the injury indicated that sulfatides-treated animals had more neutrophils adhering to the injury site than vehicle-treated controls. At 21 days, sulfatides-treated animals had a greater neointimal area than controls. In in vitro studies, sulfatides (i) increased cytosolic free calcium in mouse neutrophils, (ii) caused increases in expression of Mac-1 (CD 11 b/CD 18) on the neutrophil membrane surface in mouse whole blood. These findings suggest that neutrophil accumulation on the subendothelial matrix or adherence of platelets mediated by adhesive interactions between L- or P-selectin and sulfatides may contribute to the development of intimal hyperplasia. The neutrophil accumulation may be mediated by an increase in Mac-1 caused by the agonistic effects of sulfatides on the neutrophil membrane surface, or by an increase in L- and P-selectin ligands resulting from the binding of sulfatides onto the exposed subendothelial matrix.

Animals↗

PubMed2005

Neutrophil accumulation promotes intimal hyperplasia after photochemically induced arterial injury in mice.

The role of leukocytes in the pathogenesis of coronary arterial disease has become a focus for clinical research. The aim of this study was to determine whether neutrophil accumulation would participate in the development of intimal hyperplasia after endothelial injury in mice, and whether d-myo-inositol hexakisphosphate (phytic acid) which inhibits the binding of L- and P-selectin to sialyl Lewis(X) could inhibit the development of intimal hyperplasia. Endothelial injury was inflicted in one femoral artery via the photochemical reaction between systemically injected rose bengal and transillumination with green light (wavelength: 540 nm). Scanning electron microscopic observation at 3 days after the injury showed an increase in the number of leukocytes adhering to the injury site. Histological observation at 21 days showed that in the neutropenia group administered anti-neutrophil antibody and in the phytic acid-treated group the progression of intimal hyperplasia was significantly attenuated by comparison with the corresponding control groups. These results suggest that neutrophil accumulation contributes to the initiation and/or development of intimal hyperplasia and L- and/or P-selectin may participate in their mechanisms.

Animals↗

PubMed2005

Nerve fiber layer measurement using scanning laser polarimetry with fixed corneal compensator in normal cynomolgus monkey eyes.

PURPOSE: The purpose of this study was to examine retinal nerve fiber layer thickness in normal cynomolgus monkeys using a scanning laser polarimeter with a fixed corneal compensator (GDx FCC), and to clarify the reproducibility and symmetries (right-left differences) between both eyes for the GDx parameters. METHODS: GDx parameters were measured in 36 normal eyes of 18 cynomolgus monkeys aged 4.0-5.5 years. The retardation values (thickness parameters) at peripapillary and macular areas obtained from the GDx FCC were measured and calculated thickness, ratio, and modulation parameters in the superior and inferior quadrants. Mean and standard deviation (SD), coefficient of variation (CV), and binocular differences were obtained for each parameter from three independent measurements made during a 1-week period. Correlation between both eyes in macular retardation and baseline values, which indicated the combined minimum retardation values for the nasal and temporal quadrants, and between macular retardation and baseline values were analyzed. RESULTS: The intraocular pressure values (mean +/- SD, n = 18) obtained for the right and left eyes were 20.7 +/- 3.8 and 20.0 +/- 3.2 mm Hg, respectively (no significant differences in both eyes). No significant differences between right and left eyes were detected for any GDx parameters. All parameters showed small right-left differences. The CVs (SD/mean x 100) for all parameters were less than 10%. Highly significant correlations were seen between bilateral eyes for macular retardation (r = 0.936, p < 0.0001) or baseline values (r = 0.946, p < 0.0001). A significant correlation (r = 0.883, p < 0.0001) was also seen between macular retardation and baseline values. CONCLUSIONS: Considering individual differences in corneal birefringence, GDx parameters obtained from a GDx FCC may be useful for the objective evaluation of time-related changes in individual eyes or for binocular comparisons in cynomolgus monkeys.

Animals↗

PubMed2005

Neuroprotective effects of minocycline against in vitro and in vivo retinal ganglion cell damage.

The purpose of this study was to determine whether minocycline, a semi-synthetic tetracycline derivative, reduces (a) the in vitro neuronal damage occurring after serum deprivation in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) and/or (b) the in vivo retinal damage induced by N-methyl-D-aspartate (NMDA) intravitreal injection in mice. In addition, we examined minocycline's putative mechanisms of action against oxidative stress and endoplasmic reticulum (ER) stress. In vitro, retinal damage was induced by 24-h serum deprivation, and cell viability was measured by Hoechst 33342 staining or resazurin reduction assay. In cultures of RGC-5 cells maintained in serum-free medium for up to 24 h, the number of cells undergoing cell death was reduced by minocycline (0.2-20 microM). Serum deprivation resulted in increased oxidative stress, as revealed by an increase in the fluorescence intensity for 5-(and-6)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA), a reactive oxygen species (ROS) indicator. Minocycline at 2 and 20 microM inhibited this ROS production. However, even at 20 microM minocycline did not inhibit the retinal damage induced by tunicamycin (an ER stress inducer). Furthermore, in mice in vivo minocycline at 90 mg/kg intraperitoneally administered 60 min before an NMDA intravitreal injection reduced the NMDA-induced retinal damage. These findings indicate that minocycline has neuroprotective effects against in vitro and in vivo retinal damage, and that an inhibitory effect on ROS production may contribute to the underlying mechanisms.

Animals↗

PubMed2005

Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage.

The neuroprotective effects of minocycline-which is broadly protective in neurologic-disease models featuring cell death and is being evaluated in clinical trials-were investigated both in vitro and in vivo. For the in vivo study, focal cerebral ischemia was induced by permanent middle cerebral artery occlusion in mice. Minocycline at 90 mg/kg intraperitoneally administered 60 min before or 30 min after (but not 4 h after) the occlusion reduced infarction, brain swelling, and neurologic deficits at 24 h after the occlusion. For the in vitro studies, we used cortical-neuron cultures from rat fetuses in which neurotoxicity was induced by 24-h exposure to 500 microM glutamate. Furthermore, the effects of minocycline on oxidative stress [such as lipid peroxidation in mouse forebrain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. Minocycline significantly inhibited glutamate-induced cell death at 2 microM and lipid peroxidation and free radical scavenging at 0.2 and 2 microM, respectively. These findings indicate that minocycline has neuroprotective effects in vivo against permanent focal cerebral ischemia and in vitro against glutamate-induced cell death and that an inhibition of oxidative stress by minocycline may be partly responsible for these effects.

Animals↗

PubMed2005

Neuroprotection by Brazilian Green Propolis against In vitro and In vivo Ischemic Neuronal Damage.

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective function in vitro and/or in vivo. In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H(2)O(2)) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In mice in vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function against in vitro cell death and in vivo focal cerebral ischemia.

Journal Article↗

PubMed2005

Comparison between monkey and human visual fields using a personal computer system.

To use monkeys as models for eye diseases that may lead to blindness, we need to develop a method to precisely measure its visual field and to understand similarities and differences in visual field properties between monkeys and humans. The visual field of monkey was not measured precisely although the necessity. We established a new system with personal computers for precise measurement of the monkey visual field. Four monkeys and three humans served as subjects. The luminance-contrast sensitivity of the central 24 degrees field was measured while the subject was fixating a small spot. During the measurement, we continuously recorded the eye position, and discarded the data when fixation was broken. Reliability indices demonstrated high and stable behavioral performance by both monkeys and humans. The luminance-contrast sensitivity was highest around the fovea, and declined as eccentricity increased. The blind spot was clearly detected 15 degrees temporally. The overall sensitivity was higher in humans than in monkeys and the sensitivity dropped more sharply in the periphery in monkeys than in humans. We recommend this system as a convenient and reliable way to measure visual functions in monkeys in basic ophthalmologic research or in assessment of the drug effects on the visual field.

Adult↗

PubMed2005

Comparison of the therapeutic indexes of different molecular forms of botulinum toxin type A.

Botulinum toxin is produced by Clostridium botulinum in three different molecular-weight forms: LL toxin, 900 kDa; L toxin, 500 kDa; and M toxin, 300 kDa. We isolated the M toxin, then compared its muscle-weakening efficacy with those of L+LL toxin and BOTOX both in vitro and in vivo. The twitch tension of the mouse isolated phrenic nerve-hemidiaphragm was used for the in vitro study. For the in vivo study, grip strength was measured in the toxin-injected legs. Undesirable muscle weakening was evaluated by grip-strength measurement in the contralateral leg. Concentration-response curves for effects on the phrenic nerve-hemidiaphragm showed that M toxin was 10 times more potent than L+LL toxin. The therapeutic index in vivo was 3- to 5-times higher for M toxin than for L+LL toxin or BOTOX, indicating a greater separation for M toxin between doses with local efficacy and systemic toxicity. These findings indicate that the M toxin preparation may have a better pharmacological profile than the conventional preparation.

Animals↗

PubMed2005

Continuous monitoring of circadian variations in intraocular pressure by telemetry system throughout a 12-week treatment with timolol maleate in rabbits.

AIM: The aim of this study was to examine the effect of a 12-week treatment with two formulations of timolol maleate on the amplitude of the circadian fluctuation in intraocular pressure (IOP). METHODS: Conscious Japanese White rabbits housed under a controlled 12-hour light-dark cycle were used. IOP was measured by a telemetry system. Each animal was treated topically for 12 weeks with 0.5% timolol solution (TM) twice-daily, 0.5% timolol gel-forming solution (TM-gel) once-daily, or saline twice-daily, and the circadian variation in IOP was measured every week. RESULTS: Administration of TM or TM-gel did not change IOP in the light phase, but significantly reduced it in the dark phase in each of the 12 weeks. The IOP reductions at 2 h after administration in the TM and TM-gel groups over the 12 weeks were, respectively, 3.6 +/- 0.3 mmHg and 3.4 +/- 0.2 mmHg versus the Saline group. The amplitudes of the circadian fluctuations in IOP in the TM group in weeks 3, 6, and 12 were 15%, 15%, and 18% smaller than those in the Saline group, while the corresponding values for the TM-gel group were 18%, 16%, and 19%, respectively. CONCLUSIONS: TM-gel administered once-daily was as effective at lowering IOP as TM administrated twice-daily over the 12-week experimental period. This study reveals that, in rabbits, both formulations of the timolol maleate induced significant IOP reductions in the dark phase and decreased the amplitudes of the circadian fluctuations in IOP for 12 successive weeks.

Adrenergic beta-Antagonists↗

PubMed2005

Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage.

Bunazosin hydrochloride is a potent and selective alpha1-adrenoceptor antagonist that has been clinically used both as a systemic antihypertensive as well as an ocular hypotensive drug. In a number of studies, we have examined some effects of bunazosin hydrochloride that might indicate its potential as an anti-glaucoma drug. In normal rabbit eyes, topically instilled bunazosin hydrochloride reached the posterior retina by local penetration at concentrations sufficient to attenuate the phenylephrine- or endothelin-1 (ET-1)-induced constriction of retinal arteries. Furthermore, bunazosin hydrochloride improved the impairment of optic nerve head (ONH) blood flow, the prolongation of visual-evoked potentials (VEP) implicit time, the enlargement of the optic disk cup, and the decrease in the number of retinal ganglion cell layer cells induced by repeated injections of ET-1 in rabbits. Topically instilled bunazosin hydrochloride improved the reductions in ONH capillary blood flow and VEP amplitude induced in rabbit eyes by nitric oxide synthase inhibition. In rat primary retinal cultures, bunazosin hydrochloride reduced glutamate-induced neuronal cell death, presumably through a Na+ channel blocking effect. In healthy humans, topically instilled bunazosin hydrochloride reportedly increases blood velocity in the ONH, retina and choroid, without significantly altering either blood pressure or heart rate. These results indicate that bunazosin hydrochloride exerts both an improvement effect within the ocular circulation and a direct neuroprotective effect. Hence, bunazosin hydrochloride may be useful as a therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal vascular occlusive diseases) that are associated with disturbances of the ocular circulation.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2004

Neuroprotective effects of beta-secretase inhibitors against rat retinal ganglion cell death.

Beta-secretase, an enzyme participating in amyloid beta-peptide generation, is thought to be involved in the pathogenesis of Alzheimer's disease. We examined the effects of beta-secretase inhibitors such as N-benzyloxycarbonyl-Val-Leu-leucinal (Z-VLL-CHO) and H-EVNstatineVAEF-NH2 (GL-189) on glutamate-induced retinal ganglion cell (RGC) death in vitro. In cultures of purified RGCs from neonatal rats, 2-day exposure to 25 microM glutamate induced RGC death, and Z-VLL-CHO (100 nM) and GL-189 (1 microM) had neuroprotective effects. We also found out that Z-VLL-CHO showed a neuroprotective effect on retinal damage induced by optic nerve crush in vivo. Thus, beta-secretase could be a potential target for therapy of neurodegenerative retinal diseases.

Amyloid Precursor Protein Secretases↗

PubMed2004

Alterations in neurofilament light in optic nerve in rat kainate and monkey ocular hypertension models.

The purpose of this study is to evaluate the changes in neurofilament light (NF-L) protein in the optic nerve in rat kainate and monkey ocular hypertension models. In the rat model, optic nerve damage was induced by kainate injection into the vitreous body. In the monkey model, photocoagulation of the trabecular meshwork led to laser-induced ocular hypertension. NF-L in optic nerve extract was quantified by quantitative immunoblot using an imaging analyzer. The amount of NF-L in optic nerve was compared between normal and kainate-treated groups at 7 days after kainate injection. Specimens from rat optic nerves and retinas were evaluated histologically to examine the correlations between damage and amount of NF-L in the optic nerve. In monkeys, the amount of NF-L in the optic nerve was compared between control fellow and ocular hypertensive eyes. Injection of kainate induced morphological optic nerve and retinal damage in rats. The amount of NF-L in the optic nerve was significantly reduced in kainate-treated eyes (vs. normal eyes). The amount of NF-L correlated with the cell count in the ganglion cell layer and the axon number in the optic nerve at 7 days after kainate injection. Further, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non N-methyl-D-aspartate receptor antagonist, suppressed the kainate-induced reduction in NF-L and retinal damage. In the monkey model, ocular hypertension and morphological optic nerve damage were shown by laser-treated eyes. The amount of NF-L in the optic nerve was reduced in laser-treated eyes. In conclusion, in rat kainate and monkey ocular hypertension models, immunoblot evaluation of NF-L shows the reduction of the amount of NF-L in the optic nerves of treated-eyes. The amount of NF-L correlated with the morphological retinal and optic nerve damage in rats. These findings indicate that immunoblot evaluation of NF-L in the optic nerve may provide a quantitative index of optic nerve damage.

6-Cyano-7-nitroquinoxaline-2,3-dione↗