Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main ...Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main risk factor.Thus,neuroprotective strategies have gained interest.We performed a bibliometric analysis to determine global publishing trends and relationships among prolific authors,publications,institutions,funding agencies,and journals.We also analyzed author keywords to identify research hotspots in glaucoma neuroprotection.Further,based on keyword analysis,we reviewed most recent literature to understand mechanistic pathways underlying glaucomarelated pathophysiological responses leading to RGC loss.Bibliographic data were sourced from Scopus.Basic bibliographic features were characterized using Scopus’s functions.VOSviewer was used for mapping and visualizing bibliometric networks.The analysis included trends in publications since 2000,the most prolific countries,institutions,authors,and the strength of their linkages.A significant increase in publication output over the past two decades was noted.The United States leads in funding support,research output,and citation links,followed by China and the UK.Among the top 10 most cited authors,three are from Japanese institutions.Keyword analysis shows a focus on molecular targets related to ischemia,excitotoxicity,inflammation,and oxidative stress,with fewer emerging drug candidates and limited clinical trials.Based on the most recent literature,emerging molecular targets underlying these key pathophysiological mechanisms are summarized.In conclusion,while pathophysiology and molecular mechanisms are the current focus,there is not much progress in developing new drug candidates and conducting clinical trials.展开更多
AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl trans...AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.展开更多
Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against N-methyl-D-aspartate(NMDA)-induced retinal cell apoptosis.The current study investigated the involvement of nuclear factor kappa-B(NF-κB...Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against N-methyl-D-aspartate(NMDA)-induced retinal cell apoptosis.The current study investigated the involvement of nuclear factor kappa-B(NF-κB),p53 and AP-1 family members(c-Jun/c-Fos)in neuroprotection by MgAT against NMDA-induced retinal damage.In this study,Sprague-Dawley rats were randomized to undergo intravitreal injection of vehicle,NMDA or MgAT as pre-treatment to NMDA.Seven days after injections,retinal ganglion cells survival was detected using retrograde labelling with fluorogold and BRN3A immunostaining.Functional outcome of retinal damage was assessed using electroretinography,and the mechanisms underlying antiapoptotic effect of MgAT were investigated through assessment of retinal gene expression of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos)using reverse transcription-polymerase chain reaction.Retinal phospho-NF-κB,phospho-p53 and AP-1 levels were evaluated using western blot assay.Rat visual functions were evaluated using visual object recognition tests.Both retrograde labelling and BRN3A immunostaining revealed a significant increase in the number of retinal ganglion cells in rats receiving intravitreal injection of MgAT compared with the rats receiving intravitreal injection of NMDA.Electroretinography indicated that pre-treatment with MgAT partially preserved the functional activity of NMDA-exposed retinas.MgAT abolished NMDA-induced increase of retinal phospho-NF-κB,phospho-p53 and AP-1 expression and suppressed NMDA-induced transcriptional activity of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos).Visual object recognition tests showed that MgAT reduced difficulties in recognizing the visual cues(i.e.objects with different shapes)after NMDA exposure,suggesting that visual functions of rats were relatively preserved by pre-treatment with MgAT.In conclusion,pre-treatment with MgAT prevents NMDA induced retinal injury by inhibiting NMDA-induced neuronal apoptosis via downregulation of transcriptional activity of NF-κB,p53 and AP-1-mediated c-Jun/c-Fos.The experiments were approved by the Animal Ethics Committee of Universiti Teknologi MARA(UiTM),Malaysia,UiTM CARE No 118/2015 on December 4,2015 and UiTM CARE No 220/7/2017 on December 8,2017 and Ethics Committee of Belgorod State National Research University,Russia,No 02/20 on January 10,2020.展开更多
Endothelin-1（ET-1）, a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine（TAU）, a naturally occurring free amino acid, is known for its neuropro...Endothelin-1（ET-1）, a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine（TAU）, a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co-or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.展开更多
Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotro...Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.展开更多
Glaucoma is a range of progressive optic neuropathies characterized by progressive retinal ganglion cell loss and visual field defects.It is recognized as a leading cause of irreversible blindness affecting more than ...Glaucoma is a range of progressive optic neuropathies characterized by progressive retinal ganglion cell loss and visual field defects.It is recognized as a leading cause of irreversible blindness affecting more than 70 million people worldwide.Currently,reduction of intraocular pressure,a widely recognized risk factor for glaucoma development,is the only pharmacological strategy for slowing down retinal ganglion cell loss and disease progression.However,retinal ganglion cell death and visual field loss have been observed in normotensive glaucoma,suggesting that the disease process is partially independent of intraocular pressure.Taurine is one of the agents that have attracted attention of researchers recently.Taurine has been shown to be involved in multiple cellular functions,including a central role as a neurotransmitter,as a trophic factor in the central nervous system development,as an osmolyte,as a neuromodulator,and as a neuroprotectant.It also plays a role in the maintenance of the structural integrity of the membranes and in the regulation of calcium transport and homeostasis.Taurine is known to prevent N-methyl-D-aspartic acid-induced excitotoxic injury to retinal ganglion cells.A recently published study clearly demonstrated that taurine prevents retinal neuronal apoptosis both in vivo and in vitro.Protective effect of taurine may be attributed to direct inhibition of apoptosis,an activation of brain derived neurotrophic factor-related neuroprotective mechanisms and reduction of retinal oxidative and nitrosative stresses.Further studies are needed to fully explore the potential of taurine as a neuroprotective agent,so that it can be applied in clinical practice,particularly for the treatment of glaucoma.The objective of current review was to summarize recent evidence on neuroprotective properties of taurine in glaucoma.展开更多
AIM: To investigate dose-dependent effects of N-methylD-aspartate(NMDA) on retinal and optic nerve morphology in rats.METHODS: Sprague Dawley rats, 180-250 g in weight were divided into four groups. Groups 1, 2, 3 and...AIM: To investigate dose-dependent effects of N-methylD-aspartate(NMDA) on retinal and optic nerve morphology in rats.METHODS: Sprague Dawley rats, 180-250 g in weight were divided into four groups. Groups 1, 2, 3 and 4 were intravitreally administered with vehicle and NMDA at the doses 80, 160 and 320 nmol respectively. Seven days after injection, rats were euthanized, and their eyes were taken for optic nerve toluidine blue and retinal hematoxylin and eosin stainings. The TUNEL assay was done for detecting apoptotic cells.RESULTS: All groups treated with NMDA showed significantly reduced ganglion cell layer(GCL) thickness within inner retina, as compared to control group. Group NMDA 160 nmol showed a significantly greater GCL thickness than the group NMDA 320 nmol. Administration of NMDA also resulted in a dose-dependent decrease in the number of nuclei both per 100 μm GCL length and per 100 μm2 of GCL. Intravitreal NMDA injection caused dosedependent damage to the optic nerve. The degeneration of nerve fibres with increased clearing of cytoplasm was observed more prominently as the NMDA dose increased. In accordance with the results of retinal morphometry analysis and optic nerve grading, TUNEL staining demonstrated NMDA-induced excitotoxic retinal injury in a dose-dependent manner.CONCLUSION: Our results demonstrate dose-dependent effects of NMDA on retinal and optic nerve morphology in rats that may be attributed to differences in the severity of excitotoxicity and oxidative stress. Our results also suggest that care should be taken while making dose selections experimentally so that the choice might best uphold study objectives.展开更多
Glaucoma is the second leading cause of irreversible vision impairment affecting more than 70 million people worldwide with approximately 10%suffering from glaucoma-related bilateral blind（Quigley and Broman,2006）.I...Glaucoma is the second leading cause of irreversible vision impairment affecting more than 70 million people worldwide with approximately 10%suffering from glaucoma-related bilateral blind（Quigley and Broman,2006）.It is a multi-factorial disease that is characterized by optic nerve damage and visual field loss.Progressive loss of retinal ganglion cells（RGCs）resulting in visual field deficits is the hallmark of glaucoma.展开更多
基金Supported by the Ministry of Higher Education(Malaysia)(No.FRGS/1/2023/SKK15/IMU/01/1)International Medical University[No.PHMS I-2023(01)].
文摘Glaucoma,a degenerative optic neuropathy,causes retinal ganglion cell(RGC)apoptosis and irreversible vision loss.Current therapies often fail to stop disease progression despite lowering intraocular pressure,the main risk factor.Thus,neuroprotective strategies have gained interest.We performed a bibliometric analysis to determine global publishing trends and relationships among prolific authors,publications,institutions,funding agencies,and journals.We also analyzed author keywords to identify research hotspots in glaucoma neuroprotection.Further,based on keyword analysis,we reviewed most recent literature to understand mechanistic pathways underlying glaucomarelated pathophysiological responses leading to RGC loss.Bibliographic data were sourced from Scopus.Basic bibliographic features were characterized using Scopus’s functions.VOSviewer was used for mapping and visualizing bibliometric networks.The analysis included trends in publications since 2000,the most prolific countries,institutions,authors,and the strength of their linkages.A significant increase in publication output over the past two decades was noted.The United States leads in funding support,research output,and citation links,followed by China and the UK.Among the top 10 most cited authors,three are from Japanese institutions.Keyword analysis shows a focus on molecular targets related to ischemia,excitotoxicity,inflammation,and oxidative stress,with fewer emerging drug candidates and limited clinical trials.Based on the most recent literature,emerging molecular targets underlying these key pathophysiological mechanisms are summarized.In conclusion,while pathophysiology and molecular mechanisms are the current focus,there is not much progress in developing new drug candidates and conducting clinical trials.
基金Supported by grant from Fundamental Research Grant Scheme by Ministry of Higher Education(MoHE)600-IRMI/FRGS 5/3(101/2019).
文摘AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.
基金supported by Ministry of Higher education,Government of Malaysia,under the grant No.RAGS/2013/UITM/SKK03/2[UiTM file no.600-RMI/RAGS 5/3(103/2013)]the Institut Pengurusan Penyelidikan(RMI),Universiti Teknologi MARA,Malaysia,under the grant 600-IRMI/MyRA 5/3/LESTARI(0088/2016).
文摘Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against N-methyl-D-aspartate(NMDA)-induced retinal cell apoptosis.The current study investigated the involvement of nuclear factor kappa-B(NF-κB),p53 and AP-1 family members(c-Jun/c-Fos)in neuroprotection by MgAT against NMDA-induced retinal damage.In this study,Sprague-Dawley rats were randomized to undergo intravitreal injection of vehicle,NMDA or MgAT as pre-treatment to NMDA.Seven days after injections,retinal ganglion cells survival was detected using retrograde labelling with fluorogold and BRN3A immunostaining.Functional outcome of retinal damage was assessed using electroretinography,and the mechanisms underlying antiapoptotic effect of MgAT were investigated through assessment of retinal gene expression of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos)using reverse transcription-polymerase chain reaction.Retinal phospho-NF-κB,phospho-p53 and AP-1 levels were evaluated using western blot assay.Rat visual functions were evaluated using visual object recognition tests.Both retrograde labelling and BRN3A immunostaining revealed a significant increase in the number of retinal ganglion cells in rats receiving intravitreal injection of MgAT compared with the rats receiving intravitreal injection of NMDA.Electroretinography indicated that pre-treatment with MgAT partially preserved the functional activity of NMDA-exposed retinas.MgAT abolished NMDA-induced increase of retinal phospho-NF-κB,phospho-p53 and AP-1 expression and suppressed NMDA-induced transcriptional activity of NF-κB,p53 and AP-1 family members(c-Jun/c-Fos).Visual object recognition tests showed that MgAT reduced difficulties in recognizing the visual cues(i.e.objects with different shapes)after NMDA exposure,suggesting that visual functions of rats were relatively preserved by pre-treatment with MgAT.In conclusion,pre-treatment with MgAT prevents NMDA induced retinal injury by inhibiting NMDA-induced neuronal apoptosis via downregulation of transcriptional activity of NF-κB,p53 and AP-1-mediated c-Jun/c-Fos.The experiments were approved by the Animal Ethics Committee of Universiti Teknologi MARA(UiTM),Malaysia,UiTM CARE No 118/2015 on December 4,2015 and UiTM CARE No 220/7/2017 on December 8,2017 and Ethics Committee of Belgorod State National Research University,Russia,No 02/20 on January 10,2020.
基金the financial support by Universiti Teknologi MARA under grant No.600-IRMI/DANA5/3/BESTARI(006/2017)
文摘Endothelin-1（ET-1）, a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine（TAU）, a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co-or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.
基金supported by the Ministry of Higher Education,Government of Malaysia,No.FRGS/2/2014/SG03/UITM/02/2 UiTM IRMI file No.600-RMI/FRGS 5/3(111/2014),toⅡYayasan Penyelidikan Otak,Minda dan Neurosains Malaysia(YPOMNM),No.YPOMNM/2019-04(2)UiTM IRMI No.100-IRMI/PRI 16/6/2(010/2019),to MAML。
文摘Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.
基金This work was financially supported by the Institut Pengurusan Penyelidikan(RMI),Universiti Teknologi MARA,Malaysia,under grants 600-IRMI/MyRA 5/3/BESTARI(004/2017)and 600-IRMI/MyRA 5/3/BESTARI(006/2017).
文摘Glaucoma is a range of progressive optic neuropathies characterized by progressive retinal ganglion cell loss and visual field defects.It is recognized as a leading cause of irreversible blindness affecting more than 70 million people worldwide.Currently,reduction of intraocular pressure,a widely recognized risk factor for glaucoma development,is the only pharmacological strategy for slowing down retinal ganglion cell loss and disease progression.However,retinal ganglion cell death and visual field loss have been observed in normotensive glaucoma,suggesting that the disease process is partially independent of intraocular pressure.Taurine is one of the agents that have attracted attention of researchers recently.Taurine has been shown to be involved in multiple cellular functions,including a central role as a neurotransmitter,as a trophic factor in the central nervous system development,as an osmolyte,as a neuromodulator,and as a neuroprotectant.It also plays a role in the maintenance of the structural integrity of the membranes and in the regulation of calcium transport and homeostasis.Taurine is known to prevent N-methyl-D-aspartic acid-induced excitotoxic injury to retinal ganglion cells.A recently published study clearly demonstrated that taurine prevents retinal neuronal apoptosis both in vivo and in vitro.Protective effect of taurine may be attributed to direct inhibition of apoptosis,an activation of brain derived neurotrophic factor-related neuroprotective mechanisms and reduction of retinal oxidative and nitrosative stresses.Further studies are needed to fully explore the potential of taurine as a neuroprotective agent,so that it can be applied in clinical practice,particularly for the treatment of glaucoma.The objective of current review was to summarize recent evidence on neuroprotective properties of taurine in glaucoma.
基金Supported by Universiti Teknologi MARA [No.600-IRMI/MYRA5/3/BESTARI (004/2017) No.600IRMI/DANA5/3/LESTARI (0076/2016) No.600-IRMI/ My RA5/3/LESTARI (0088/2016)]
文摘AIM: To investigate dose-dependent effects of N-methylD-aspartate(NMDA) on retinal and optic nerve morphology in rats.METHODS: Sprague Dawley rats, 180-250 g in weight were divided into four groups. Groups 1, 2, 3 and 4 were intravitreally administered with vehicle and NMDA at the doses 80, 160 and 320 nmol respectively. Seven days after injection, rats were euthanized, and their eyes were taken for optic nerve toluidine blue and retinal hematoxylin and eosin stainings. The TUNEL assay was done for detecting apoptotic cells.RESULTS: All groups treated with NMDA showed significantly reduced ganglion cell layer(GCL) thickness within inner retina, as compared to control group. Group NMDA 160 nmol showed a significantly greater GCL thickness than the group NMDA 320 nmol. Administration of NMDA also resulted in a dose-dependent decrease in the number of nuclei both per 100 μm GCL length and per 100 μm2 of GCL. Intravitreal NMDA injection caused dosedependent damage to the optic nerve. The degeneration of nerve fibres with increased clearing of cytoplasm was observed more prominently as the NMDA dose increased. In accordance with the results of retinal morphometry analysis and optic nerve grading, TUNEL staining demonstrated NMDA-induced excitotoxic retinal injury in a dose-dependent manner.CONCLUSION: Our results demonstrate dose-dependent effects of NMDA on retinal and optic nerve morphology in rats that may be attributed to differences in the severity of excitotoxicity and oxidative stress. Our results also suggest that care should be taken while making dose selections experimentally so that the choice might best uphold study objectives.
基金supported by Institut Pengurusan Penyelidikan(RMI)Universiti Teknologi MARA,Malaysia,under the grant No.600-IRMI/MyRA 5/3/LESTARI(0088/2016)and 600-IRMI/DANA 5/3/LESTARI(0076/2016)
文摘Glaucoma is the second leading cause of irreversible vision impairment affecting more than 70 million people worldwide with approximately 10%suffering from glaucoma-related bilateral blind（Quigley and Broman,2006）.It is a multi-factorial disease that is characterized by optic nerve damage and visual field loss.Progressive loss of retinal ganglion cells（RGCs）resulting in visual field deficits is the hallmark of glaucoma.
