Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa ...Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa TAR DNA-binding protein(pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART,Alzheimer's disease(AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages[ 0 and B IV, and a Thal phase of 0(no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus,stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.展开更多
Background:Age-related macular degeneration(AMD)and diabetic retinopathy(DR)are among the leading causes of blindness in the United States and other developed countries.Early detection is the key to prevention and eff...Background:Age-related macular degeneration(AMD)and diabetic retinopathy(DR)are among the leading causes of blindness in the United States and other developed countries.Early detection is the key to prevention and effective treatment.We have built an artificial intelligence-based screening system which utilizes a cloud-based platform for combined large scale screening through primary care settings for early diagnosis of these diseases.Methods:iHealthScreen Inc.,an independent medical software company,has developed automated AMD and DR screening systems utilizing a telemedicine platform based on deep machine learning techniques.For both diseases,we prospectively imaged both eyes of 340 unselected non-dilated subjects over 50 years of age.For DR specifically,152 diabetic patients at New York Eye and Ear faculty retina practices,ophthalmic and primary care clinics in New York city with color fundus cameras.Following the initial review of the images,308 images with other confounding conditions like high myopia and vascular occlusion,and poor quality were excluded,leaving 676 eligible images for AMD and DR evaluation.Three ophthalmologists evaluated each of the images,and after adjudication,the patients were determined referrable or non-referable for AMD DR.Concerning AMD,172 were labeled referable(intermediate or late),and 504 were non-referable(no or early).Concurrently,regarding DR,33 were referable(moderate or worse),and 643 were non-referable(none or mild).All images were uploaded to iHealthScreen’s telemedicine platform and analyzed by the automated systems for both diseases.The system performances are tested on per eye basis with sensitivity,specificity,accuracy,and kappa scores with respect to the professional graders.Results:In identifying referable DR,the system achieved a sensitivity of 97.0%and a specificity of 96.3%,and a kappa score of 0.70 on this prospective dataset.For AMD,the sensitivity was 86.6%,the specificity of 92.1%,and a kappa score of 0.76.Conclusions:The AMD and DR screening tools achieved excellent performance operating together to identify two retinal diseases prospectively in mixed datasets,demonstrating the feasibility of such tools in the early diagnosis of eye diseases.These early screening tools will help create an even more comprehensive system capable of being trained on other retinal pathologies,a goal within reach for public health deployment.展开更多
Clinical ophthalmologists consider each retinal disease as a completely unique entity.However,various retinal diseases,such as uveitis,age-related macular degeneration,diabetic retinopathy,and primary open-angle glauc...Clinical ophthalmologists consider each retinal disease as a completely unique entity.However,various retinal diseases,such as uveitis,age-related macular degeneration,diabetic retinopathy,and primary open-angle glaucoma,share a number of common pathogenetic pathways.Whether a retinal disease initiates from direct injury to the blood-retinal barrier(BRB)or a defect/injury to retinal neurons or glia that impairs the BRB secondarily,the BRB is a pivotal point in determining the prognosis as self-limiting and recovering,or developing and progressing to a clinical phenotype.The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB,which underlies its pivotal role in the initiation and development of common retinal diseases.展开更多
Background:Loss of cells in the human trabecular meshwork(TM)has been reported with ageing and in glaucoma.This study aims to identify,quantify and determine the age-related changes of human TM stem cells(TMSCs).Metho...Background:Loss of cells in the human trabecular meshwork(TM)has been reported with ageing and in glaucoma.This study aims to identify,quantify and determine the age-related changes of human TM stem cells(TMSCs).Methods:Isolation of TM cells/paraffin sectioning was carried out using human corneoscleral rings and whole globes.The TM cells/sections were immunostained for the stem cell markers ATP-binding cassette protein G2(ABCG2),nerve growth factor receptor p75 and AnkyrinG(AnkG).Images were acquired using Leica SP8 confocal microscope.The isolated cells were analyzed for two parameters-ABCG2 expression and nucleus to cytoplasmic ratio(N/C ratio).The total number of TM cells and those positive for ABCG2 and p75 in each section were quantified.Spearman rank order correlation was used to determine the association between age and the cell counts.Results:The TMSCs were identified based on two parameters-high ABCG2 expression and high N/C ratio>0.7.These stem cells were also positive for p75 and AnkG.The TMSC content based on the two parameters was 21.0±1.4%in<30 years age group,12.6±6.6%in 30–60 years and 4.0±3.5%in>60 years.The stem cells with high ABCG2 and p75 expression were restricted to the Schwalbe’s line region of the TM.A significant correlation was observed between the reduction in TMSC content and TM cell count during ageing.Conclusion:The human TMSCs were identified and quantified based on two parameter analysis.This study established a significant association between age-related reduction in TMSC content and TM cell loss.展开更多
基金supported by the National Science Foundation China(91632109 to JHZ,KQZ and HJH)the Zhejiang Provincial Natural Science Foundation(LY16H090013 to KQZ)the Zhejiang Medical and Health Science and Technology Plan Project(WKJ20132-009 to KQZ)
文摘Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa TAR DNA-binding protein(pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART,Alzheimer's disease(AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages[ 0 and B IV, and a Thal phase of 0(no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus,stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.
基金This project was supported by NIH SBIR Grant:1R44EY031202.
文摘Background:Age-related macular degeneration(AMD)and diabetic retinopathy(DR)are among the leading causes of blindness in the United States and other developed countries.Early detection is the key to prevention and effective treatment.We have built an artificial intelligence-based screening system which utilizes a cloud-based platform for combined large scale screening through primary care settings for early diagnosis of these diseases.Methods:iHealthScreen Inc.,an independent medical software company,has developed automated AMD and DR screening systems utilizing a telemedicine platform based on deep machine learning techniques.For both diseases,we prospectively imaged both eyes of 340 unselected non-dilated subjects over 50 years of age.For DR specifically,152 diabetic patients at New York Eye and Ear faculty retina practices,ophthalmic and primary care clinics in New York city with color fundus cameras.Following the initial review of the images,308 images with other confounding conditions like high myopia and vascular occlusion,and poor quality were excluded,leaving 676 eligible images for AMD and DR evaluation.Three ophthalmologists evaluated each of the images,and after adjudication,the patients were determined referrable or non-referable for AMD DR.Concerning AMD,172 were labeled referable(intermediate or late),and 504 were non-referable(no or early).Concurrently,regarding DR,33 were referable(moderate or worse),and 643 were non-referable(none or mild).All images were uploaded to iHealthScreen’s telemedicine platform and analyzed by the automated systems for both diseases.The system performances are tested on per eye basis with sensitivity,specificity,accuracy,and kappa scores with respect to the professional graders.Results:In identifying referable DR,the system achieved a sensitivity of 97.0%and a specificity of 96.3%,and a kappa score of 0.70 on this prospective dataset.For AMD,the sensitivity was 86.6%,the specificity of 92.1%,and a kappa score of 0.76.Conclusions:The AMD and DR screening tools achieved excellent performance operating together to identify two retinal diseases prospectively in mixed datasets,demonstrating the feasibility of such tools in the early diagnosis of eye diseases.These early screening tools will help create an even more comprehensive system capable of being trained on other retinal pathologies,a goal within reach for public health deployment.
基金grants from the Major Project of National Natural Science Foundation of China(NSFC)-Guangdong Province Joint Fund(No.3030902113080)the Science and Technology Planning Project of Guangdong Province(No.303090100502050-18)the Guangzhou Science and Technology Plan Project(Nos.201803040020 and 201903010065)。
文摘Clinical ophthalmologists consider each retinal disease as a completely unique entity.However,various retinal diseases,such as uveitis,age-related macular degeneration,diabetic retinopathy,and primary open-angle glaucoma,share a number of common pathogenetic pathways.Whether a retinal disease initiates from direct injury to the blood-retinal barrier(BRB)or a defect/injury to retinal neurons or glia that impairs the BRB secondarily,the BRB is a pivotal point in determining the prognosis as self-limiting and recovering,or developing and progressing to a clinical phenotype.The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB,which underlies its pivotal role in the initiation and development of common retinal diseases.
基金supported by the Science and Engineering Research Board(Project reference number:EMR/2016/002351).
文摘Background:Loss of cells in the human trabecular meshwork(TM)has been reported with ageing and in glaucoma.This study aims to identify,quantify and determine the age-related changes of human TM stem cells(TMSCs).Methods:Isolation of TM cells/paraffin sectioning was carried out using human corneoscleral rings and whole globes.The TM cells/sections were immunostained for the stem cell markers ATP-binding cassette protein G2(ABCG2),nerve growth factor receptor p75 and AnkyrinG(AnkG).Images were acquired using Leica SP8 confocal microscope.The isolated cells were analyzed for two parameters-ABCG2 expression and nucleus to cytoplasmic ratio(N/C ratio).The total number of TM cells and those positive for ABCG2 and p75 in each section were quantified.Spearman rank order correlation was used to determine the association between age and the cell counts.Results:The TMSCs were identified based on two parameters-high ABCG2 expression and high N/C ratio>0.7.These stem cells were also positive for p75 and AnkG.The TMSC content based on the two parameters was 21.0±1.4%in<30 years age group,12.6±6.6%in 30–60 years and 4.0±3.5%in>60 years.The stem cells with high ABCG2 and p75 expression were restricted to the Schwalbe’s line region of the TM.A significant correlation was observed between the reduction in TMSC content and TM cell count during ageing.Conclusion:The human TMSCs were identified and quantified based on two parameter analysis.This study established a significant association between age-related reduction in TMSC content and TM cell loss.
