Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear mechanism.Microglial polarization and neuroinflammation play an important role in retinal degeneration.Our study aimed to explo...Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear mechanism.Microglial polarization and neuroinflammation play an important role in retinal degeneration.Our study aimed to explore the function of microglial polarization during glaucoma progression and identify a strategy to alleviate retinal neuroinflammation.Retinal ischemia/reperfusion injury was induced in C57BL/6 mice.In a separate cohort of animals,interleukin(IL)-4(50 ng/mL,2μL per injection)or vehicle was intravitreally injected after retinal ischemia/reperfusion injury.RGC loss was assessed by counting cells that were positive for the RGC marker RNA binding protein,mRNA processing factor in retinal flat mounts.The expression of classically activated(M1)and alternatively activated(M2)microglial markers were assessed by quantitative reverse transcription-polymerase chain reaction,immunofluorescence,and western blotting.The results showed that progressive RGC loss was accompanied by a continuous decrease in M2 microglia during the late phase of the 28-day period after retinal ischemia/reperfusion injury.IL-4 was undetectable in the retina at all time points,and intravitreal IL-4 administration markedly improved M2 microglial marker expression and ameliorated RGC loss in the late phase post-retinal ischemia/reperfusion injury.In summary,we observed that IL-4 treatment maintained a high number of M2 microglia after RIR and promoted RGC survival.展开更多
Astragaloside Ⅳ is the main active compound of Astragalus membranaceus. Astragaloside Ⅳ has strong anti-oxidative activities and protective effects against progression of peripheral neuropathy. In this study, we det...Astragaloside Ⅳ is the main active compound of Astragalus membranaceus. Astragaloside Ⅳ has strong anti-oxidative activities and protective effects against progression of peripheral neuropathy. In this study, we determined whether astragaloside Ⅳ protects retinal ganglion cells（RGC） from oxidative stress injury using the rat RGC-5 cell line. Hydrogen peroxide（H_2O_2） was used to induce oxidative stress injury, with the protective effect of astragaloside Ⅳ examined. Cell Counting Kit-8 and 4′,6-diamidino-2-phenylindole staining showed that astragaloside Ⅳ increased cell survival rate and decreased apoptotic cell number. Flow cytometry showed that astragaloside Ⅳ decreased H_2O_2-induced reactive oxygen species levels. While laser confocal microscopy showed that astragaloside Ⅳ inhibited the H_2O_2-induced decrease of mitochondrial membrane potential. Western blot assay showed that astragaloside Ⅳ reduced cytochrome c release induced by H_2O_2, inhibited Bax and caspase-3 expression, and increased Bcl-2 expression. Altogether, these results indicate that astragaloside Ⅳ has potential protective effects against H_2O_2-induced oxidative stress in retinal ganglion cells.展开更多
Glaucoma, the leading cause globally of irreversible blindness, is a neurodegenerative disease characterized by progressive retinal ganglion cell death. To date, no drug has been shown to prevent the retinal ganglion ...Glaucoma, the leading cause globally of irreversible blindness, is a neurodegenerative disease characterized by progressive retinal ganglion cell death. To date, no drug has been shown to prevent the retinal ganglion cell loss associated with glaucoma. Multiple mechanisms lead to ganglion cell death in glaucoma, suggesting that a neuroprotectant that has a single mode of action, like memantine, would have a limited positive effect at slowing down ganglion cell death. Conversely simultaneously targeting several factors may be the best therapeutic approach to improve outcomes Multifunctional drugs are fast gaining acceptance as a strategy for the treatment of complex disorders of the central nervous system, such as Parkinson＇s disease, Alzheimer＇s disease and other progressive neurodegenerative diseases. In this paper, we review the current literature on multifunctional drugs and propose a rationale for the use of multifunctional drugs in glaucomatous optic neuropathy.展开更多
基金supported by the National Natural Science Foundation of China, No.81970796(to WYG)Clinical Research Program of the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No.JYLJ201905(to WYG)Interdisciplinary Program of Shanghai Jiao Tong University, No.YG2019QNA18(to YW)
文摘Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear mechanism.Microglial polarization and neuroinflammation play an important role in retinal degeneration.Our study aimed to explore the function of microglial polarization during glaucoma progression and identify a strategy to alleviate retinal neuroinflammation.Retinal ischemia/reperfusion injury was induced in C57BL/6 mice.In a separate cohort of animals,interleukin(IL)-4(50 ng/mL,2μL per injection)or vehicle was intravitreally injected after retinal ischemia/reperfusion injury.RGC loss was assessed by counting cells that were positive for the RGC marker RNA binding protein,mRNA processing factor in retinal flat mounts.The expression of classically activated(M1)and alternatively activated(M2)microglial markers were assessed by quantitative reverse transcription-polymerase chain reaction,immunofluorescence,and western blotting.The results showed that progressive RGC loss was accompanied by a continuous decrease in M2 microglia during the late phase of the 28-day period after retinal ischemia/reperfusion injury.IL-4 was undetectable in the retina at all time points,and intravitreal IL-4 administration markedly improved M2 microglial marker expression and ameliorated RGC loss in the late phase post-retinal ischemia/reperfusion injury.In summary,we observed that IL-4 treatment maintained a high number of M2 microglia after RIR and promoted RGC survival.
基金supported by a grant from the Education Department of Heilongjiang Province of China,No.12541398
文摘Astragaloside Ⅳ is the main active compound of Astragalus membranaceus. Astragaloside Ⅳ has strong anti-oxidative activities and protective effects against progression of peripheral neuropathy. In this study, we determined whether astragaloside Ⅳ protects retinal ganglion cells（RGC） from oxidative stress injury using the rat RGC-5 cell line. Hydrogen peroxide（H_2O_2） was used to induce oxidative stress injury, with the protective effect of astragaloside Ⅳ examined. Cell Counting Kit-8 and 4′,6-diamidino-2-phenylindole staining showed that astragaloside Ⅳ increased cell survival rate and decreased apoptotic cell number. Flow cytometry showed that astragaloside Ⅳ decreased H_2O_2-induced reactive oxygen species levels. While laser confocal microscopy showed that astragaloside Ⅳ inhibited the H_2O_2-induced decrease of mitochondrial membrane potential. Western blot assay showed that astragaloside Ⅳ reduced cytochrome c release induced by H_2O_2, inhibited Bax and caspase-3 expression, and increased Bcl-2 expression. Altogether, these results indicate that astragaloside Ⅳ has potential protective effects against H_2O_2-induced oxidative stress in retinal ganglion cells.
基金supported by the National Natural Science Foundation of China, No. 81000380the Scientific Research Fund of Health Department, Hubei Province, China, No. QJX2010-53
文摘Glaucoma, the leading cause globally of irreversible blindness, is a neurodegenerative disease characterized by progressive retinal ganglion cell death. To date, no drug has been shown to prevent the retinal ganglion cell loss associated with glaucoma. Multiple mechanisms lead to ganglion cell death in glaucoma, suggesting that a neuroprotectant that has a single mode of action, like memantine, would have a limited positive effect at slowing down ganglion cell death. Conversely simultaneously targeting several factors may be the best therapeutic approach to improve outcomes Multifunctional drugs are fast gaining acceptance as a strategy for the treatment of complex disorders of the central nervous system, such as Parkinson＇s disease, Alzheimer＇s disease and other progressive neurodegenerative diseases. In this paper, we review the current literature on multifunctional drugs and propose a rationale for the use of multifunctional drugs in glaucomatous optic neuropathy.
