AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a go...AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes.展开更多
BACKGROUND Cataracts remain a prime reason for visual disturbance and blindness all over the world,despite the capacity for successful surgical replacement with artificial lenses.Diabetic cataract(DC),a metabolic comp...BACKGROUND Cataracts remain a prime reason for visual disturbance and blindness all over the world,despite the capacity for successful surgical replacement with artificial lenses.Diabetic cataract(DC),a metabolic complication,usually occurs at an earlier age and progresses faster than age-related cataracts.Evidence has linked N6-methyladenosine(m6A)to DC progression.However,there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis.AIM To elucidate the role played by altered m6A and differentially expressed mRNAs(DEmRNAs)in DC.METHODS Anterior lens capsules were collected from the control subjects and patients with DC.M6A epitranscriptomic microarray was performed to investigate the altered m6A modifications and determine the DEmRNAs.Through Gene Ontology and pathway enrichment(Kyoto Encyclopedia of Genes and Genomes)analyses,the potential role played by dysregulated m6A modification was predicted.Real-time polymerase chain reaction was further carried out to identify the dysregulated expression of RNA methyltransferases,demethylases,and readers.RESULTS Increased m6A abundance levels were found in the total mRNA of DC samples.Bioinformatics analysis predicted that ferroptosis pathways could be associated with m6A-modified mRNAs.The levels of five methylation-related genes-RBM15,WTAP,ALKBH5,FTO,and YTHDF1-were upregulated in DC samples.Upregulation of RBM15 expression was verified in SRA01/04 cells with high-glucose medium and in samples from DC patients.CONCLUSION M6a mRNA modifications may be involved in DC progression via the ferroptosis pathway,rendering novel insights into therapeutic strategies for DC.展开更多
Background:Diabetic cataract is a common complication and a lens disorder in diabetes.Moreover,Dendrobium officinale polysaccharide(DOP)is found to alleviate diabetes complications.Consequently,microRNA-125b and mitog...Background:Diabetic cataract is a common complication and a lens disorder in diabetes.Moreover,Dendrobium officinale polysaccharide(DOP)is found to alleviate diabetes complications.Consequently,microRNA-125b and mitogen-activated protein kinase signaling pathways play significant roles in diabetes.However,the mechanism and the effect of DOP on diabetic cataract remains unknown.Methods:Wistar male rats were randomly assigned to the control,model,and DOP groups.Diabetes was induced with streptozotocin.Furthermore,DOP was orally given for 12 weeks.The Lens Opacities Classification System III was used to evaluate lens opacity by slit-lamp microscope.The lens was then harvested for testing the mRNA expression of microRNA-125b,ERK1,ERK2,Raf and Ras using reverse transcription-polymerase chain reaction.The protein expression of ERK1,ERK2,Raf,and Ras was detected using the Western blot analysis.The targets of microRNA-125b were predicted in miRWalk 2.0.These targets were obtained from the Kyoto Encyclopedia of Genes and Genomes pathway.Results:The lens opacities of the rats in the control group were almost at C0N0.Moreover,the majority of the lens opacities in the model group were C3 to C4 and N1 to N2,and were mostly at C1 to C2 and N0 to N1 in the DOP group.The difference was statistically significant(P<0.05).Furthermore,the microRNA-125b expression in the model group is significantly higher compared with the control group.Conversely,the microRNA-125b expression in the DOP group is significantly decreased(all P<0.05).The mRNA expression of ERK1,ERK2,Raf,and Ras in the model groups were upregulated compared with those of the control group.However,the ERK1 and Raf mRNA expressions of the DOP group were lower compared with the model group(all P<0.05).The protein expression of ERK1,Raf,and Ras in the model group was significantly increased compared with those of the control group.The protein expression of ERK1,Raf,and Ras in the DOP group was significantly lower compared with the model group(all P<0.05).Moreover,3,378 genes of the microRNA-125b target were gained from the miRWalk.After Kyoto Encyclopedia of Genes and Genomes pathways analysis in Gene Set Enrichment Analysis,246 items were gained including Ras(rno04014)and mitogen-activated protein kinase(rno04010)signaling pathways.A positive correlation exists between microRNA-125b and mRNA expression of ERK1,ERK2,Raf and Ras(r=0.940,0.841,0.666,and 0.768;all P<0.05).Conclusion:DOP can alleviate the severity of the opacity of the lens in diabetic cataract rats via microRNA-125b and mitogen-activated protein kinase signaling pathways.Thus,microRNA-125b has something to do with the mitogen-activated protein kinase signaling pathway.展开更多
BACKGROUND Diabetic patients with cataracts encounter specific difficulties during cataract surgery due to alterations in microcirculation,blood supply,metabolism,and the microenvironment.Traditional phacoemulsificati...BACKGROUND Diabetic patients with cataracts encounter specific difficulties during cataract surgery due to alterations in microcirculation,blood supply,metabolism,and the microenvironment.Traditional phacoemulsification may not fully tackle these issues,especially in instances with substantial preoperative astigmatism.The utilization of femtosecond laser-assisted phacoemulsification,in conjunction with Toric intraocular lens(IOL)implantation,offers a potentially more efficient strategy.This research seeks to evaluate the efficacy and possible complications of this approach in diabetic cataract patients.AIM To investigate the clinical efficacy and complications of femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation in diabetic cataract patients,comparing it with traditional phacoemulsification methods.METHODS This retrospective study enrolled 120 patients with diabetes cataract from May 2019 to May 2021.The patients were divided into two groups:the control group underwent traditional phacoemulsification and Toric IOL implantation,while the treatment group received Len Sx femtosecond laser-assisted treatment.Outcome measures included naked eye vision,astigmatism,high-level ocular phase difference detection,clinical efficacy,and complication.RESULTS There were no significant preoperative differences in astigmatism or naked eyesight between the two groups.However,postoperative improvements were observed in both groups,with the treatment group showing greater enhancements in naked eye vision and astigmatism six months after the procedure.High-level corneal phase difference tests also indicated significant differences in favor of the treatment group.CONCLUSION This study suggests that femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation appears to be more effective in enhancing postoperative vision in diabetic cataract patients compared to traditional methods offering valuable insights for clinical practice.展开更多
Background:Cataract is a blinding disease worldwide.It is an age-related disease that mainly occurs in people over 65 years old.Cataract is also prevalent in patients with diabetes mellites(DM).The pathological mechan...Background:Cataract is a blinding disease worldwide.It is an age-related disease that mainly occurs in people over 65 years old.Cataract is also prevalent in patients with diabetes mellites(DM).The pathological mechanisms underlying diabetic cataract(DC)are more complex than that of age-related cataract.Studies have identified that polyol pathway,advanced glycation end products(AGEs)and oxidative stress are the primary pathogenesis of DC.In recent years,molecular-level regulations and pathological processes of lens epithelial cells(LECs)have been confirmed to play roles in the initiation and progression of DC.A comprehensive understanding and elucidation of how chronic hyperglycemia drives molecular-level regulations and cytopathological processes in the lens will shed lights on the prevention,delay and treatment of DC.Main text:Excessive glucose in the lens enhances polyol pathway and AGEs formation.Polyol pathway causes imbalance in the ratio of NADPH/NADPt and NADH/NADt.Decrease in NADPH/NADPt ratio compromises antioxidant enzymes,while increase in NADH/NADt ratio promotes reactive oxygen species(ROS)overproduction in mitochondria,resulting in oxidative stress.Oxidative stress in the lens causes oxidation of DNA,proteins and lipids,leading to abnormalities in their structure and functions.Glycation of proteins by AGEs decreases solubility of proteins.High glucose triggered epigenetic regulations directly or indirectly affect expressions of genes and proteins in LECs.Changes in autophagic activity,increases in fibrosis and apoptosis of LECs destroy the morphological structure and physiological functions of the lens epithelium,disrupting lens homeostasis.Conclusions:In both diabetic animal models and diabetics,oxidative stress plays crucial roles in the formation of cataract.Epigenetic regulations,include lncRNA,circRNA,microRNA,methylation of RNA and DNA,histone acetylation and pathological processes,include autophagy,fibrosis and apoptosis of LECs also involved in DC.展开更多
Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of...Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of the human eye that causes cataracts is managed by the Aldose Reductase Enzyme(AR),and it is been found that AR inhibitors may mitigate the onset of diabetic cataracts.There exists a large pool of natural and synthetic AR inhibitors that can prevent diabetic complications,and the development of a machine-learning(ML)prediction model may bring new AR inhibitors with better characteristics into clinical use.Methods:Using known AR inhibitors and their chemical-physical descriptors we created the ML model for prediction of new AR inhibitors.The predicted inhibitors were tested by computational docking to the binding site of AR.Results:Using cross-validation in order to find the most accurate ML model,we ended with final cross-validation accuracy of 90%.Computational docking testing of the predicted inhibitors gave a high level of correlation between the ML prediction score and binding free energy.Conclusions:Currently known AR inhibitors are not used yet for patients for several reasons.We think that new predicted AR inhibitors have the potential to possess more favorable characteristics to be successfully implemented after clinical testing.Exploring new inhibitors can improve patient well-being and lower surgical complications all while decreasing long-term medical expenses.展开更多
Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epid...Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.展开更多
AIM:To investigate whether Wild Field Imaging System(WFIS SW-8000),25G endoilluminator,and intraoperative optical coherence tomography(iOCT)can perform realtime screening and diagnosing in patients with suspicious dia...AIM:To investigate whether Wild Field Imaging System(WFIS SW-8000),25G endoilluminator,and intraoperative optical coherence tomography(iOCT)can perform realtime screening and diagnosing in patients with suspicious diabetic retinopathy(DR)during phacoemulsification,especially in cases of white cataract.METHODS:A cross-sectional study was carried out.A total of 204 dense diabetic cataractous eyes of 204 patients with suspected DR treated from April 2020 to March 2021 were included.Phacoemulsification combined with intraocular lens implantation was performed.Following the removal of the lens opacity,the 25G endoilluminator,fundus photography,and iOCT were performed successively.Optical coherence tomography(OCT)and/or fundus fluorescein angiography(FFA)were used to verify the fundus findings postoperatively.Intraoperative and postoperative results were compared to verify the accuracy of intraoperative diagnosis in each group.RESULTS:Intraoperative and postoperative examinations revealed 58 and 62 eyes with DR,respectively(positive rate,28.43%and 30.39%,respectively).During the phacoemulsification,WFIS SW-8000 detected 44 eyes with DR(the detection rate,70.97%);25G endo-illuminator found 56 eyes with DR(the detection rate,90.32%);iOCT found 46 eyes with DR(the detection rate,74.19%);and 58 eyes with DR were found by combining the three methods(the detection rate,93.55%).There were statistically significant differences in the diagnostic sensitivity for DR among the methods(χ^(2)=16.36,P=0.001).CONCLUSION:WFIS SW-8000,25G endo-illuminator,iOCT,and especially their combination can be used to inspect the fundus and detect DR intraoperatively;they are helpful for the timely diagnosis and treatment of DR in patients with dense cataract.展开更多
AIM:To investigate the role of exosomal miR-29b and Ca^(2+)in regulating the function of human lens epithelial cells(HLECs).METHODS:Exosomes were isolated from human aqueous humour(AH)by ultracentrifugation,and visual...AIM:To investigate the role of exosomal miR-29b and Ca^(2+)in regulating the function of human lens epithelial cells(HLECs).METHODS:Exosomes were isolated from human aqueous humour(AH)by ultracentrifugation,and visualized by nanopar ticle tracking and transmission electron microscopy.Exosomal miRNA sequencing was performed to identify differentially expressed miRNAs between diabetes with cataracts(DMC)group and age-related cataracts(ARC)group.TargetScan was used to predict potential target of certain miRNA.The expression of CACNA1C mRNA was determined by quantitative real-time polymerase chain reaction and CACNA1C protein was determined by Western blotting.Concentration of Ca^(2+)in human AH and the culture supernatant of cells were detected by the calcium assay kit.Cell counting kit-8 was used to determine cell viability.RESULTS:Exosomes were isolated from human AH,which had a typical cup-shaped phenotype and a particle size distribution in accordance with micro extracellular vesicles.Exosomal miRNA sequencing revealed that miR-29b was significantly downregulated in DMC group compared with ARC.Ca^(2+)concentration of human AH in DMC was higher than that in ARC.The culture supernatant of cells transfected with miR-29b inhibitors had a higher concentration of Ca^(2+)than that transfected with miR-29b mimics.miR-29b reduced the viability of HLECs by upregulating CACNA1C expression.CONCLUSION:Exosomes isolated from human AH contains abundant miRNAs.A significantly expressed miR NA,miR-29b,can affect the concentration of Ca^(2+)and regulate HLEC processes by upregulating CACNA1C.展开更多
Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase(AR).Hence,AR inhibitors are considered as potential agents in the m...Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase(AR).Hence,AR inhibitors are considered as potential agents in the management of diabetic cataract.This study explored the AR inhibition potential of Hemidesmus indicus var.pubescens root extract by in silico and ex vivo methods.Molecular docking studies(Auto Dock tool)betweenβ-sitosterol,hemidesminine,hemidesmin-1,hemidesmin-2,and AR showed thatβ-sitosterol(−10.2 kcal/mol)and hemidesmin-2(−8.07 kcal/mol)had the strongest affinity to AR enzyme.Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose(55 mM)as cataract inducing agent at room temperature(pH 7.8)for 72 h.After treatment with Vitamin E acetate−100μg/mL(standard)and test extract(500 and 1000μg/mL)separately,the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels.Additionally,extract also normalized the levels of antioxidant markers like SOD,CAT,GSH.Our results showed evidence that H.indicus var.pubescens root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications.展开更多
文摘AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes.
基金Supported by the National Natural Science Foundation of China,No.82171039.
文摘BACKGROUND Cataracts remain a prime reason for visual disturbance and blindness all over the world,despite the capacity for successful surgical replacement with artificial lenses.Diabetic cataract(DC),a metabolic complication,usually occurs at an earlier age and progresses faster than age-related cataracts.Evidence has linked N6-methyladenosine(m6A)to DC progression.However,there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis.AIM To elucidate the role played by altered m6A and differentially expressed mRNAs(DEmRNAs)in DC.METHODS Anterior lens capsules were collected from the control subjects and patients with DC.M6A epitranscriptomic microarray was performed to investigate the altered m6A modifications and determine the DEmRNAs.Through Gene Ontology and pathway enrichment(Kyoto Encyclopedia of Genes and Genomes)analyses,the potential role played by dysregulated m6A modification was predicted.Real-time polymerase chain reaction was further carried out to identify the dysregulated expression of RNA methyltransferases,demethylases,and readers.RESULTS Increased m6A abundance levels were found in the total mRNA of DC samples.Bioinformatics analysis predicted that ferroptosis pathways could be associated with m6A-modified mRNAs.The levels of five methylation-related genes-RBM15,WTAP,ALKBH5,FTO,and YTHDF1-were upregulated in DC samples.Upregulation of RBM15 expression was verified in SRA01/04 cells with high-glucose medium and in samples from DC patients.CONCLUSION M6a mRNA modifications may be involved in DC progression via the ferroptosis pathway,rendering novel insights into therapeutic strategies for DC.
基金supported by Fujian Provincial Natural Science Foundation Project(No.2019J01483)Fujian Provincial Health and Health Commission Medical Innovation Project(No.2018-CXB-15)of China。
文摘Background:Diabetic cataract is a common complication and a lens disorder in diabetes.Moreover,Dendrobium officinale polysaccharide(DOP)is found to alleviate diabetes complications.Consequently,microRNA-125b and mitogen-activated protein kinase signaling pathways play significant roles in diabetes.However,the mechanism and the effect of DOP on diabetic cataract remains unknown.Methods:Wistar male rats were randomly assigned to the control,model,and DOP groups.Diabetes was induced with streptozotocin.Furthermore,DOP was orally given for 12 weeks.The Lens Opacities Classification System III was used to evaluate lens opacity by slit-lamp microscope.The lens was then harvested for testing the mRNA expression of microRNA-125b,ERK1,ERK2,Raf and Ras using reverse transcription-polymerase chain reaction.The protein expression of ERK1,ERK2,Raf,and Ras was detected using the Western blot analysis.The targets of microRNA-125b were predicted in miRWalk 2.0.These targets were obtained from the Kyoto Encyclopedia of Genes and Genomes pathway.Results:The lens opacities of the rats in the control group were almost at C0N0.Moreover,the majority of the lens opacities in the model group were C3 to C4 and N1 to N2,and were mostly at C1 to C2 and N0 to N1 in the DOP group.The difference was statistically significant(P<0.05).Furthermore,the microRNA-125b expression in the model group is significantly higher compared with the control group.Conversely,the microRNA-125b expression in the DOP group is significantly decreased(all P<0.05).The mRNA expression of ERK1,ERK2,Raf,and Ras in the model groups were upregulated compared with those of the control group.However,the ERK1 and Raf mRNA expressions of the DOP group were lower compared with the model group(all P<0.05).The protein expression of ERK1,Raf,and Ras in the model group was significantly increased compared with those of the control group.The protein expression of ERK1,Raf,and Ras in the DOP group was significantly lower compared with the model group(all P<0.05).Moreover,3,378 genes of the microRNA-125b target were gained from the miRWalk.After Kyoto Encyclopedia of Genes and Genomes pathways analysis in Gene Set Enrichment Analysis,246 items were gained including Ras(rno04014)and mitogen-activated protein kinase(rno04010)signaling pathways.A positive correlation exists between microRNA-125b and mRNA expression of ERK1,ERK2,Raf and Ras(r=0.940,0.841,0.666,and 0.768;all P<0.05).Conclusion:DOP can alleviate the severity of the opacity of the lens in diabetic cataract rats via microRNA-125b and mitogen-activated protein kinase signaling pathways.Thus,microRNA-125b has something to do with the mitogen-activated protein kinase signaling pathway.
文摘BACKGROUND Diabetic patients with cataracts encounter specific difficulties during cataract surgery due to alterations in microcirculation,blood supply,metabolism,and the microenvironment.Traditional phacoemulsification may not fully tackle these issues,especially in instances with substantial preoperative astigmatism.The utilization of femtosecond laser-assisted phacoemulsification,in conjunction with Toric intraocular lens(IOL)implantation,offers a potentially more efficient strategy.This research seeks to evaluate the efficacy and possible complications of this approach in diabetic cataract patients.AIM To investigate the clinical efficacy and complications of femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation in diabetic cataract patients,comparing it with traditional phacoemulsification methods.METHODS This retrospective study enrolled 120 patients with diabetes cataract from May 2019 to May 2021.The patients were divided into two groups:the control group underwent traditional phacoemulsification and Toric IOL implantation,while the treatment group received Len Sx femtosecond laser-assisted treatment.Outcome measures included naked eye vision,astigmatism,high-level ocular phase difference detection,clinical efficacy,and complication.RESULTS There were no significant preoperative differences in astigmatism or naked eyesight between the two groups.However,postoperative improvements were observed in both groups,with the treatment group showing greater enhancements in naked eye vision and astigmatism six months after the procedure.High-level corneal phase difference tests also indicated significant differences in favor of the treatment group.CONCLUSION This study suggests that femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation appears to be more effective in enhancing postoperative vision in diabetic cataract patients compared to traditional methods offering valuable insights for clinical practice.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.81873674 and 82070947).
文摘Background:Cataract is a blinding disease worldwide.It is an age-related disease that mainly occurs in people over 65 years old.Cataract is also prevalent in patients with diabetes mellites(DM).The pathological mechanisms underlying diabetic cataract(DC)are more complex than that of age-related cataract.Studies have identified that polyol pathway,advanced glycation end products(AGEs)and oxidative stress are the primary pathogenesis of DC.In recent years,molecular-level regulations and pathological processes of lens epithelial cells(LECs)have been confirmed to play roles in the initiation and progression of DC.A comprehensive understanding and elucidation of how chronic hyperglycemia drives molecular-level regulations and cytopathological processes in the lens will shed lights on the prevention,delay and treatment of DC.Main text:Excessive glucose in the lens enhances polyol pathway and AGEs formation.Polyol pathway causes imbalance in the ratio of NADPH/NADPt and NADH/NADt.Decrease in NADPH/NADPt ratio compromises antioxidant enzymes,while increase in NADH/NADt ratio promotes reactive oxygen species(ROS)overproduction in mitochondria,resulting in oxidative stress.Oxidative stress in the lens causes oxidation of DNA,proteins and lipids,leading to abnormalities in their structure and functions.Glycation of proteins by AGEs decreases solubility of proteins.High glucose triggered epigenetic regulations directly or indirectly affect expressions of genes and proteins in LECs.Changes in autophagic activity,increases in fibrosis and apoptosis of LECs destroy the morphological structure and physiological functions of the lens epithelium,disrupting lens homeostasis.Conclusions:In both diabetic animal models and diabetics,oxidative stress plays crucial roles in the formation of cataract.Epigenetic regulations,include lncRNA,circRNA,microRNA,methylation of RNA and DNA,histone acetylation and pathological processes,include autophagy,fibrosis and apoptosis of LECs also involved in DC.
文摘Purpose:Patients with diabetes mellitus have an elevated chance of developing cataracts,a degenerative visionimpairing condition often needing surgery.The process of the reduction of glucose to sorbitol in the lens of the human eye that causes cataracts is managed by the Aldose Reductase Enzyme(AR),and it is been found that AR inhibitors may mitigate the onset of diabetic cataracts.There exists a large pool of natural and synthetic AR inhibitors that can prevent diabetic complications,and the development of a machine-learning(ML)prediction model may bring new AR inhibitors with better characteristics into clinical use.Methods:Using known AR inhibitors and their chemical-physical descriptors we created the ML model for prediction of new AR inhibitors.The predicted inhibitors were tested by computational docking to the binding site of AR.Results:Using cross-validation in order to find the most accurate ML model,we ended with final cross-validation accuracy of 90%.Computational docking testing of the predicted inhibitors gave a high level of correlation between the ML prediction score and binding free energy.Conclusions:Currently known AR inhibitors are not used yet for patients for several reasons.We think that new predicted AR inhibitors have the potential to possess more favorable characteristics to be successfully implemented after clinical testing.Exploring new inhibitors can improve patient well-being and lower surgical complications all while decreasing long-term medical expenses.
基金supported by the National Natural Science Foundation of China,No.82122009 (to JX)Science Research Foundation ofAier Eye Hospital Group,No.AM2001D1 (to JX)the Natural Science Foundation of Hunan Province,No.2020JJ5002 (to SJ)。
文摘Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.
基金Supported by National Natural Science Foundation of China(No.81974129)the Technology and Science Foundation of Jiangsu Province(No.2016699)+1 种基金the Technology and Science Foundation of Nantong(No.22019012No.2019078).
文摘AIM:To investigate whether Wild Field Imaging System(WFIS SW-8000),25G endoilluminator,and intraoperative optical coherence tomography(iOCT)can perform realtime screening and diagnosing in patients with suspicious diabetic retinopathy(DR)during phacoemulsification,especially in cases of white cataract.METHODS:A cross-sectional study was carried out.A total of 204 dense diabetic cataractous eyes of 204 patients with suspected DR treated from April 2020 to March 2021 were included.Phacoemulsification combined with intraocular lens implantation was performed.Following the removal of the lens opacity,the 25G endoilluminator,fundus photography,and iOCT were performed successively.Optical coherence tomography(OCT)and/or fundus fluorescein angiography(FFA)were used to verify the fundus findings postoperatively.Intraoperative and postoperative results were compared to verify the accuracy of intraoperative diagnosis in each group.RESULTS:Intraoperative and postoperative examinations revealed 58 and 62 eyes with DR,respectively(positive rate,28.43%and 30.39%,respectively).During the phacoemulsification,WFIS SW-8000 detected 44 eyes with DR(the detection rate,70.97%);25G endo-illuminator found 56 eyes with DR(the detection rate,90.32%);iOCT found 46 eyes with DR(the detection rate,74.19%);and 58 eyes with DR were found by combining the three methods(the detection rate,93.55%).There were statistically significant differences in the diagnostic sensitivity for DR among the methods(χ^(2)=16.36,P=0.001).CONCLUSION:WFIS SW-8000,25G endo-illuminator,iOCT,and especially their combination can be used to inspect the fundus and detect DR intraoperatively;they are helpful for the timely diagnosis and treatment of DR in patients with dense cataract.
基金the National Natural Science Foundation of China(No.81870645)。
文摘AIM:To investigate the role of exosomal miR-29b and Ca^(2+)in regulating the function of human lens epithelial cells(HLECs).METHODS:Exosomes were isolated from human aqueous humour(AH)by ultracentrifugation,and visualized by nanopar ticle tracking and transmission electron microscopy.Exosomal miRNA sequencing was performed to identify differentially expressed miRNAs between diabetes with cataracts(DMC)group and age-related cataracts(ARC)group.TargetScan was used to predict potential target of certain miRNA.The expression of CACNA1C mRNA was determined by quantitative real-time polymerase chain reaction and CACNA1C protein was determined by Western blotting.Concentration of Ca^(2+)in human AH and the culture supernatant of cells were detected by the calcium assay kit.Cell counting kit-8 was used to determine cell viability.RESULTS:Exosomes were isolated from human AH,which had a typical cup-shaped phenotype and a particle size distribution in accordance with micro extracellular vesicles.Exosomal miRNA sequencing revealed that miR-29b was significantly downregulated in DMC group compared with ARC.Ca^(2+)concentration of human AH in DMC was higher than that in ARC.The culture supernatant of cells transfected with miR-29b inhibitors had a higher concentration of Ca^(2+)than that transfected with miR-29b mimics.miR-29b reduced the viability of HLECs by upregulating CACNA1C expression.CONCLUSION:Exosomes isolated from human AH contains abundant miRNAs.A significantly expressed miR NA,miR-29b,can affect the concentration of Ca^(2+)and regulate HLEC processes by upregulating CACNA1C.
文摘Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase(AR).Hence,AR inhibitors are considered as potential agents in the management of diabetic cataract.This study explored the AR inhibition potential of Hemidesmus indicus var.pubescens root extract by in silico and ex vivo methods.Molecular docking studies(Auto Dock tool)betweenβ-sitosterol,hemidesminine,hemidesmin-1,hemidesmin-2,and AR showed thatβ-sitosterol(−10.2 kcal/mol)and hemidesmin-2(−8.07 kcal/mol)had the strongest affinity to AR enzyme.Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose(55 mM)as cataract inducing agent at room temperature(pH 7.8)for 72 h.After treatment with Vitamin E acetate−100μg/mL(standard)and test extract(500 and 1000μg/mL)separately,the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels.Additionally,extract also normalized the levels of antioxidant markers like SOD,CAT,GSH.Our results showed evidence that H.indicus var.pubescens root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications.
