AIM:To investigate whether pyroptosis contributes to retinal ganglion cell(RGC)degeneration in aged TgAPPswePS1 transgenic mice and to explore the relationship between amyloid-beta(Aβ)accumulation and activation of t...AIM:To investigate whether pyroptosis contributes to retinal ganglion cell(RGC)degeneration in aged TgAPPswePS1 transgenic mice and to explore the relationship between amyloid-beta(Aβ)accumulation and activation of the pyroptotic pathway in the retina.METHODS:The twelve 18-month-old TgAPPswePS1 transgenic mice and twelve 18-month-old wild-type C57BL/6J mice were used to investigate amyloid precursor protein(APP)and Aβexpression,retinal structural changes,and activation of pyroptosis in RGCs.Immunohistochemical analyses were performed to detect APP,Aβ,and pyroptosisrelated proteins[NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,gasdermin D(GSDMD),interleukin(IL)-1β,and IL-18].Quantitative assessments of retinal nerve fiber layer(RNFL)thickness were conducted to evaluate retinal integrity.RESULTS:Compared to age-matched wild-type controls,TgAPPswePS1 transgenic mice exhibited significant upregulation of APP and Aβwithin RGCs.Histological analysis revealed reduced RNFL thickness,indicating structural degeneration.Notably,RGCs in transgenic mice showed robust immunoreactivity for NLRP3,caspase-1,and GSDMD,alongside elevated levels of IL-1βand IL-18,supporting the activation of pyroptosis.CONCLUSION:Aβaccumulation in RGCs is associated with retinal degeneration and activation of the pyroptosis pathway in aged TgAPPswePS1 mice.This study provides new insights into the inflammatory mechanisms underlying Aβ-related retinal neurodegeneration and suggests that targeting pyroptosis may represent a promising therapeutic strategy for retinal disorders linked to amyloid pathology.展开更多
基金Supported by Natural Science Foundation of Zhejiang Province(No.LY18H120009)Wenzhou Basic Scientific Research Project(No.2025K0279)+1 种基金Xi’an Health and Wellness Committee General Cultivation Project(No.2023ms08)Shaanxi Province Health and Health High-Level Talents(Team)Training Program Young Talents Project.
文摘AIM:To investigate whether pyroptosis contributes to retinal ganglion cell(RGC)degeneration in aged TgAPPswePS1 transgenic mice and to explore the relationship between amyloid-beta(Aβ)accumulation and activation of the pyroptotic pathway in the retina.METHODS:The twelve 18-month-old TgAPPswePS1 transgenic mice and twelve 18-month-old wild-type C57BL/6J mice were used to investigate amyloid precursor protein(APP)and Aβexpression,retinal structural changes,and activation of pyroptosis in RGCs.Immunohistochemical analyses were performed to detect APP,Aβ,and pyroptosisrelated proteins[NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,gasdermin D(GSDMD),interleukin(IL)-1β,and IL-18].Quantitative assessments of retinal nerve fiber layer(RNFL)thickness were conducted to evaluate retinal integrity.RESULTS:Compared to age-matched wild-type controls,TgAPPswePS1 transgenic mice exhibited significant upregulation of APP and Aβwithin RGCs.Histological analysis revealed reduced RNFL thickness,indicating structural degeneration.Notably,RGCs in transgenic mice showed robust immunoreactivity for NLRP3,caspase-1,and GSDMD,alongside elevated levels of IL-1βand IL-18,supporting the activation of pyroptosis.CONCLUSION:Aβaccumulation in RGCs is associated with retinal degeneration and activation of the pyroptosis pathway in aged TgAPPswePS1 mice.This study provides new insights into the inflammatory mechanisms underlying Aβ-related retinal neurodegeneration and suggests that targeting pyroptosis may represent a promising therapeutic strategy for retinal disorders linked to amyloid pathology.
