High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat ...High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.展开更多
Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years.A major challenge of cancer vaccine is to targe...Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years.A major challenge of cancer vaccine is to target cytosols of dendritic cells(DCs)in the lymph nodes(LNs)to enhance efficiency of antigen cross-presentation,which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells.Here,we address this issue by conjugating ovalbumin(OVA)to PEG-PCL using disulfide bond(-ss-),and the degradable pH-responsive polymer-PEI-PCL as delivery carrier.In addition,the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs.Subsequently,CpG ODN_(1826),a TLR-9 agonist,was further introduced into a mixed micelle of 30nm or less as a unique tumor vaccine.Importantly,the results demonstrated the mixed micelles with 1:1mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs,meanwhile,OVA was modified to the surface of mixed micelles via disulfide bonds(-ss-)for promotion efficiency of antigen cross-presentation.More surprisingly,combination of tumor vaccine with anti-PD-1,the therapy of ectopic melanoma(B16-OVA)and lung metastasis melanoma(B16-OVA)is excellent therapeutic effect.Taken together,our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.展开更多
基金supported by the National Natural Science Foundation of China,No.82371051(to DW)the Natural Science Foundation of Beijing,No.7212092(to DW)+1 种基金the Capital’s Funds for Health Improvement and Research,No.2022-2-5041(to DW)the Fund of Science and Technology Development of Beijing Rehabilitation Hospital,Capital Medical University,No.2021R-001(to YL).
文摘High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.
文摘Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years.A major challenge of cancer vaccine is to target cytosols of dendritic cells(DCs)in the lymph nodes(LNs)to enhance efficiency of antigen cross-presentation,which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells.Here,we address this issue by conjugating ovalbumin(OVA)to PEG-PCL using disulfide bond(-ss-),and the degradable pH-responsive polymer-PEI-PCL as delivery carrier.In addition,the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs.Subsequently,CpG ODN_(1826),a TLR-9 agonist,was further introduced into a mixed micelle of 30nm or less as a unique tumor vaccine.Importantly,the results demonstrated the mixed micelles with 1:1mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs,meanwhile,OVA was modified to the surface of mixed micelles via disulfide bonds(-ss-)for promotion efficiency of antigen cross-presentation.More surprisingly,combination of tumor vaccine with anti-PD-1,the therapy of ectopic melanoma(B16-OVA)and lung metastasis melanoma(B16-OVA)is excellent therapeutic effect.Taken together,our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.
