The human retina serves as a light detector and signals transmission tissue.Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events....The human retina serves as a light detector and signals transmission tissue.Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events.Here,we sequenced the m RNA of over 0.6 million single cells from human retinas across six regions at nine different ages.Sixty cell sub-types have been identified from the human mature retinas with unique markers.We revealed regional and age differences of gene expression profiles within the human retina.Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells.Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types.Some of the gene’s expression,such as DKK3,are elevated in aged retinas.A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability.Overall,decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system.展开更多
Background The human immunodeficiency virus-1 （HIV-1） envelope glycoprotein gp120 has been implicated in the development of AIDS-associated retinopathy. The present study tested the hypothesis that gp120 may induce ...Background The human immunodeficiency virus-1 （HIV-1） envelope glycoprotein gp120 has been implicated in the development of AIDS-associated retinopathy. The present study tested the hypothesis that gp120 may induce oxidative stress including up regulation of inducible nitric oxide synthase （iNOS） and production of malondialdehyde （MDA） and nitric oxide （NO） to mediate retinopathy in retinal pigment epithelial （RPE） cells. Methods Human RPE cell line D407 was cultured and treated with gp120. HIV-1 gp120 protein induced lipid peroxidation product MDA. NO production and iNOS expression were examined in vitro by spectrophomtometry, real-time PCR, Western blotting, and confocal microscope. Results Addition of gp120 was able to induce RPE cells to produce NO and MDA in time- and dose-dependent manners （P 〈0.05）. Similarly, gp120 was also capable of up-regulating iNOS mRNA and protein in D407 cells in time- and dose-dependent manners. Conclusions Gp120 induces oxidative stress in D407 cell by stimulating MDA and NO production, which is mediated by up-regulating iNOS expression. Gp120 may mediate oxidation stress in AIDS-associated retinopathy.展开更多
Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human eryth...Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First,control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber,and then hypodermic injection of domestic rhEPO was made. HIF-1α protein in the retina was observed by immunohistochemical staining method on days 1,3,7 and 14 after retinal ischemia-reperfusion,respectively. Results No cells with HIF-1α positive expression were observed in the retina of the control group. Cells with HIF-1α positive expression in the model group outnumbered those in the control group (P<0.01). The resemblance pattern occurred in EPO group but its degree was slightly greater than that in the model group from day 3 after ischemia-reperfusion (P<0.05). Conclusion Domestic rhEPO can down-regulate the expression of HIF-1α in the retina with acute high intraocular pressure,which may be one of the mechanisms that rhEPO protects the retina from ischemia-reperfusion injury.展开更多
According to the American Diabetes Association,diabetes was the seventh leading cause of death,and diabetic retinopathy the leading cause of blindness in working age adults in the United States in 2010.Diabetes is cha...According to the American Diabetes Association,diabetes was the seventh leading cause of death,and diabetic retinopathy the leading cause of blindness in working age adults in the United States in 2010.Diabetes is characterized by hyperglycemia associated with either hypoinsulinemia or insulin resistance,and over time,this chronic metabolic condition may lead to various complications including kidney failure,heart attacks,and retinal degeneration.In order to better understand the molecular basis of this disease and its complications,animal models have been the primary approach used to investigate the effects of diabetes on various tissues or cell types of the body,including the retina.However,inherent to these animal models are critical limitations that make the insight gained from these models challenging to apply to the human pathology.These difficulties in translating the knowledge obtained from animal studies have led a growing number of research groups to explore the diabetes complications,especially diabetic retinopathy,on tissues from human donors.This review summarizes the data collected from diabetic patients at various stages of diabetic retinopathy and classifies the data based upon their relevance to the main aspects of diabetic retinopathy:retinal vasculature dysfunction,inflammation,and neurodegeneration.This review discusses the importance of those studies to discriminate and establish the relevance of the findings obtained from animal models but also the limitations of such approaches.展开更多
目的:探讨重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对急性高眼压视网膜缺血所致的视神经和视网膜超微结构损害的保护作用。方法:将12只健康新西兰白兔平均分为模型组和EPO组。两组兔均任选1眼作为实验眼,用生理...目的:探讨重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对急性高眼压视网膜缺血所致的视神经和视网膜超微结构损害的保护作用。方法:将12只健康新西兰白兔平均分为模型组和EPO组。两组兔均任选1眼作为实验眼,用生理盐水前房灌注法造成急性高眼压模型。造模前第3d及造模结束时,EPO组兔皮下注射rhEPO100U/kg共两次。第7d进行视神经和视网膜的超微结构观察。结果:急性高眼压使视神经和视网膜的超微结构受到明显损害,全身使用rhEPO后这种损害显著减轻。结论:rhEPO能够减轻急性高眼压引起的视神经和视网膜超微结构损害。rhEPO可能成为新的视神经保护药物。展开更多
基金supported by the National Natural Science Foundation of China(81790643,81970839,82271105,82121003)the Sichuan Science and Technology Program(2021YFS0033,2021YFS0369,2021YFS0404,2021JDGD0036)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2019I2M-5-032)。
文摘The human retina serves as a light detector and signals transmission tissue.Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events.Here,we sequenced the m RNA of over 0.6 million single cells from human retinas across six regions at nine different ages.Sixty cell sub-types have been identified from the human mature retinas with unique markers.We revealed regional and age differences of gene expression profiles within the human retina.Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells.Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types.Some of the gene’s expression,such as DKK3,are elevated in aged retinas.A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability.Overall,decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30471851）.Acknowledgements： We are grateful to the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH for offering us HIV-1 gp120.
文摘Background The human immunodeficiency virus-1 （HIV-1） envelope glycoprotein gp120 has been implicated in the development of AIDS-associated retinopathy. The present study tested the hypothesis that gp120 may induce oxidative stress including up regulation of inducible nitric oxide synthase （iNOS） and production of malondialdehyde （MDA） and nitric oxide （NO） to mediate retinopathy in retinal pigment epithelial （RPE） cells. Methods Human RPE cell line D407 was cultured and treated with gp120. HIV-1 gp120 protein induced lipid peroxidation product MDA. NO production and iNOS expression were examined in vitro by spectrophomtometry, real-time PCR, Western blotting, and confocal microscope. Results Addition of gp120 was able to induce RPE cells to produce NO and MDA in time- and dose-dependent manners （P 〈0.05）. Similarly, gp120 was also capable of up-regulating iNOS mRNA and protein in D407 cells in time- and dose-dependent manners. Conclusions Gp120 induces oxidative stress in D407 cell by stimulating MDA and NO production, which is mediated by up-regulating iNOS expression. Gp120 may mediate oxidation stress in AIDS-associated retinopathy.
基金supported by the Science and Technology Research Foundation of Shaanxi Province, China (No.2008K14-07)the Medical and Phar macologic Research Foundation of Xi'an City, China (No.SF08004-2)
文摘Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First,control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber,and then hypodermic injection of domestic rhEPO was made. HIF-1α protein in the retina was observed by immunohistochemical staining method on days 1,3,7 and 14 after retinal ischemia-reperfusion,respectively. Results No cells with HIF-1α positive expression were observed in the retina of the control group. Cells with HIF-1α positive expression in the model group outnumbered those in the control group (P<0.01). The resemblance pattern occurred in EPO group but its degree was slightly greater than that in the model group from day 3 after ischemia-reperfusion (P<0.05). Conclusion Domestic rhEPO can down-regulate the expression of HIF-1α in the retina with acute high intraocular pressure,which may be one of the mechanisms that rhEPO protects the retina from ischemia-reperfusion injury.
文摘According to the American Diabetes Association,diabetes was the seventh leading cause of death,and diabetic retinopathy the leading cause of blindness in working age adults in the United States in 2010.Diabetes is characterized by hyperglycemia associated with either hypoinsulinemia or insulin resistance,and over time,this chronic metabolic condition may lead to various complications including kidney failure,heart attacks,and retinal degeneration.In order to better understand the molecular basis of this disease and its complications,animal models have been the primary approach used to investigate the effects of diabetes on various tissues or cell types of the body,including the retina.However,inherent to these animal models are critical limitations that make the insight gained from these models challenging to apply to the human pathology.These difficulties in translating the knowledge obtained from animal studies have led a growing number of research groups to explore the diabetes complications,especially diabetic retinopathy,on tissues from human donors.This review summarizes the data collected from diabetic patients at various stages of diabetic retinopathy and classifies the data based upon their relevance to the main aspects of diabetic retinopathy:retinal vasculature dysfunction,inflammation,and neurodegeneration.This review discusses the importance of those studies to discriminate and establish the relevance of the findings obtained from animal models but also the limitations of such approaches.
文摘目的:探讨重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对急性高眼压视网膜缺血所致的视神经和视网膜超微结构损害的保护作用。方法:将12只健康新西兰白兔平均分为模型组和EPO组。两组兔均任选1眼作为实验眼,用生理盐水前房灌注法造成急性高眼压模型。造模前第3d及造模结束时,EPO组兔皮下注射rhEPO100U/kg共两次。第7d进行视神经和视网膜的超微结构观察。结果:急性高眼压使视神经和视网膜的超微结构受到明显损害,全身使用rhEPO后这种损害显著减轻。结论:rhEPO能够减轻急性高眼压引起的视神经和视网膜超微结构损害。rhEPO可能成为新的视神经保护药物。
