AIM:To study the effect of palmitoylethanolamide(PEA)on apoptosis of retinal pigment epithelial(RPE)cells induced by all-trans retinal(at RAL)and to explore the possible molecular mechanism.METHODS:Cell Titer 96■Aque...AIM:To study the effect of palmitoylethanolamide(PEA)on apoptosis of retinal pigment epithelial(RPE)cells induced by all-trans retinal(at RAL)and to explore the possible molecular mechanism.METHODS:Cell Titer 96■Aqueous One Solution Cell Proliferation Assay(MTS)was used to detect the effect of PEA on human-derived retinal epithelial cells(ARPE-19)viability induced by at RAL.A Leica DMi8 inverted microscope was used to observe cell morphology.Reactive oxygen species(ROS)production was evaluated with 2’,7’-dichlorodihydrofluorescein diacetate(H2DCFDA)staining and fluorescence microscopy.Expression of c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),c-Jun,phosphorylated c-Jun(p-c-Jun),Bak,cleaved caspase-3,C/EBP homologous protein(CHOP),and binding(Bip)protein levels were tested by Western blot.Abca4-/-Rdh8-/-mice,mouse models of at RAL clearance defects which displays some symbolic characteristics of dry age-related macular degeneration(AMD)and Stargardt disease(STGD1).In the animal models,PEA was injected intraperitoneally.The full-field electroretinogram was used to detect visual function under scotopic conditions traced from mice.Optical coherence tomography showed reconstitution or thickening of the retinal pigment epithelium layer.Effect of PEA on fundus injury induced by light in Abca4-/-Rdh8-/-mice was observed by fundus photography.RESULTS:PEA ameliorated ARPE-19 cells apoptosis and inhibited ROS(including mitochondrial ROS)production induced by at RAL.PEA improved the retinal functional,prohibited both RPE and photoreceptor from death,ameliorates light-induced fundus impairment in Abca4-/-Rdh8-/-mice.In vitro and in vivo,PEA inhibited JNK,p-JNK,c-Jun,p-c-Jun,Bak,cleaved caspase-3,CHOP,and Bip protein levels induced by all-trans retinal in ARPE-19 cells.CONCLUSION:PEA has effect on treating RPE cells apoptosis in retinopathy caused by at RAL accumulation.PEA is a potential treatment strategy for dry AMD and STGD1.The molecular mechanism is affecting the ROS-JNKCHOP signaling pathway partly.展开更多
Age-related macular degeneration (AMD) is still an incurable blinding eye disease because of complex pathogenic mechanisms and unusual diseased regions.With the use of chemical biology tools,great progress has been ac...Age-related macular degeneration (AMD) is still an incurable blinding eye disease because of complex pathogenic mechanisms and unusual diseased regions.With the use of chemical biology tools,great progress has been achieved in improving the understanding of AMD pathogenesis.The severity of AMD is,at least in part,linked to the non-degradable lipofuscin bis-retinoids in retinal pigment epithelial (RPE).This material is thought to result from the lifelong accumulation of lysosomal residual bodies containing the end products derived from the daily phagocytosis of rod outer segments by RPE cells.Here,we present previously recognized bis-retinoids with focus on structures and biosynthetic pathways.In addition to a brief discussion on the mutual conversion relationships of bis-retinoids,future perspectives and the medical relevance of such studies on these lipofuscin constituents are also highlighted.展开更多
基金Supported by the National Natural Science Foundation of China(No.82171064,No.81870671,No.82274162)Natural Science Foundation of Fujian Province(No.2020J01013)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012514,No.2021A1515011391)。
文摘AIM:To study the effect of palmitoylethanolamide(PEA)on apoptosis of retinal pigment epithelial(RPE)cells induced by all-trans retinal(at RAL)and to explore the possible molecular mechanism.METHODS:Cell Titer 96■Aqueous One Solution Cell Proliferation Assay(MTS)was used to detect the effect of PEA on human-derived retinal epithelial cells(ARPE-19)viability induced by at RAL.A Leica DMi8 inverted microscope was used to observe cell morphology.Reactive oxygen species(ROS)production was evaluated with 2’,7’-dichlorodihydrofluorescein diacetate(H2DCFDA)staining and fluorescence microscopy.Expression of c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),c-Jun,phosphorylated c-Jun(p-c-Jun),Bak,cleaved caspase-3,C/EBP homologous protein(CHOP),and binding(Bip)protein levels were tested by Western blot.Abca4-/-Rdh8-/-mice,mouse models of at RAL clearance defects which displays some symbolic characteristics of dry age-related macular degeneration(AMD)and Stargardt disease(STGD1).In the animal models,PEA was injected intraperitoneally.The full-field electroretinogram was used to detect visual function under scotopic conditions traced from mice.Optical coherence tomography showed reconstitution or thickening of the retinal pigment epithelium layer.Effect of PEA on fundus injury induced by light in Abca4-/-Rdh8-/-mice was observed by fundus photography.RESULTS:PEA ameliorated ARPE-19 cells apoptosis and inhibited ROS(including mitochondrial ROS)production induced by at RAL.PEA improved the retinal functional,prohibited both RPE and photoreceptor from death,ameliorates light-induced fundus impairment in Abca4-/-Rdh8-/-mice.In vitro and in vivo,PEA inhibited JNK,p-JNK,c-Jun,p-c-Jun,Bak,cleaved caspase-3,CHOP,and Bip protein levels induced by all-trans retinal in ARPE-19 cells.CONCLUSION:PEA has effect on treating RPE cells apoptosis in retinopathy caused by at RAL accumulation.PEA is a potential treatment strategy for dry AMD and STGD1.The molecular mechanism is affecting the ROS-JNKCHOP signaling pathway partly.
基金supported by the National Natural Science Foundation of China(Nos.21202146 and 81271018)the Fundamental Research Funds for the Central Universities,Chinathe Zhejiang Key Laboratory Fund of China(No.2011E10006)
文摘Age-related macular degeneration (AMD) is still an incurable blinding eye disease because of complex pathogenic mechanisms and unusual diseased regions.With the use of chemical biology tools,great progress has been achieved in improving the understanding of AMD pathogenesis.The severity of AMD is,at least in part,linked to the non-degradable lipofuscin bis-retinoids in retinal pigment epithelial (RPE).This material is thought to result from the lifelong accumulation of lysosomal residual bodies containing the end products derived from the daily phagocytosis of rod outer segments by RPE cells.Here,we present previously recognized bis-retinoids with focus on structures and biosynthetic pathways.In addition to a brief discussion on the mutual conversion relationships of bis-retinoids,future perspectives and the medical relevance of such studies on these lipofuscin constituents are also highlighted.
基金Project supported by the National Natural Science Foundation of China(Nos.21202146 and 81271018)the Fundamental Research Funds for the Central Universities+1 种基金the Zhejiang Scientific Research Foundation for the Returned Overseas Chinese Scholars(No.J20120556)the Zhejiang Key Laboratory Fund of China(No.2011E10006)
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LQ17H120001)the Medical Science and Technology Program of Zhejiang Province(Nos.2016KYA195 and 2017KY714)+1 种基金the National Natural Science Foundation of China(No.81801424)the 211 Talents Training Program of Taizhou,China
