1.Research progress on the role of AMP-activated protein kinase in ocular dis-eases
Ruping WANG ; Pubo WANG ; Xiuzhen LU ; Qiuxin WU
Recent Advances in Ophthalmology 2025;45(9):731-737
Adenosine monophosphate-activated protein kinase(AMPK),acting as a"molecular switch"for cellular energy status,regulates multiple metabolic pathways to maintain energy balance and plays a crucial role in the development of various ocular diseases.This article summarizes the mechanisms of AMPK in several ophthalmic diseases and the pro-gress of related research,with a focus on age-related macular degeneration,diabetic retinopathy,and ocular surface disea-ses.By reviewing the pathogenesis of these diseases and the regulatory role of the AMPK signaling pathway,we explore the potential applications of the AMPK signaling pathway in the treatment of ophthalmic diseases and analyze the limitations and deficiencies of current research.With further investigation,regulatory strategies targeting the AMPK signaling pathway are expected to provide new ideas and potential therapies for the treatment of ophthalmic diseases in the future.
2.Current status and development of deep learning in retinal disease research
Hongzhuang CHENG ; Xinru NING ; Chuyun GUO ; Jie ZHONG
Recent Advances in Ophthalmology 2025;45(9):738-746
Objective Deep learning provides strong technical support for early diagnosis,lesion segmentation,and treatment prediction of retinal diseases,significantly improving the efficiency and accuracy of diagnosis.But it also faces challenges in terms of different applicability and performance differences of the model,mainly due to the differences in fea-ture extraction ability,computational complexity,and clinical adaptability among different network structures,which make them have different advantages and limitations in different application scenarios.By systematically searching relevant litera-ture in PubMed and Web of Science databases over the past 5 years,this article summarizes the most commonly used deep learning network architectures in common vitreoretinal diseases,summarizes their different advantages and limitations,and analyzes the best application directions of each architecture in the field of ophthalmology,providing reference and inspira-tion for future research.
3.Research progress on the role of the cGAS-STING signaling pathway in the pathogenesis of glaucoma and its targeted therapeutic strategies
Xiaojuan HUANG ; Jin ZHANG ; Hongyun YUE
Recent Advances in Ophthalmology 2025;45(9):752-756
Glaucoma is a blinding eye disease characterized by optic nerve damage and visual field defects,with a complex pathogenesis.Studies have shown that the abnormal activation of the cyclic GMP-AMP synthase-stimulator of in-terferon genes(cGAS-STING)signaling pathway may be closely related to the occurrence and development of glaucoma.New therapeutic strategies targeting this pathway,such as the cGAS small-molecule inhibitor RU.521 and the STING inhibi-tor H-151,have been shown to effectively alleviate pathological changes associated with glaucoma,and research into their mechanisms of action is becoming increasingly in-depth.This article aims to review the basic mechanisms of the cGAS-STING signaling pathway and its role in the pathogenesis of glaucoma,as well as the latest research progress of compounds targeting cGAS and STING in the treatment of glaucoma,in order to provide a new perspective for the immunotherapy of glaucoma.
4.Interpretation of the 2024 edition of the Diabetic Retinopathy Preferred Prac-tice Pattern by the American Academy of Ophthalmology
Yi SHAO ; Jiali WU ; Yixin WANG
Recent Advances in Ophthalmology 2025;45(9):673-678
Diabetic retinopathy(DR)is a common microvascular complication of diabetes and the leading cause of blindness among working-age adults globally,posing a significant public health challenge.The 2024 Diabetic Retinopathy Preferred Practice Pattern(PPP)released by the American Academy of Ophthalmology is the authoritative guideline in this field.Building on previous editions,the latest version provides comprehensive refinements,including optimized screening protocols,strengthened multifactorial risk factor management,revised disease staging criteria,and the integration of preci-sion-based treatment strategies,aiming to enhance the quality of DR management.This article offers a detailed interpreta-tion of the PPP 2024,in an attempt to serve as a key reference for ophthalmologists in diagnostic and therapeutic decision-making.
5.DCLRE1A regulates mitochondrial biogenesis and participates in the develop-ment of age-related cataracts
Chenghao SUN ; Miaomiao WU ; Pengfei LI ; Min JI ; Huaijin GUAN
Recent Advances in Ophthalmology 2025;45(9):679-683
Objective To investigate the effects of DNA Cross-Link Repair 1A(DCLRE1A)on mitochondrial func-tion in lens epithelial cells(LECs).Methods Thirty eyes from 30 patients with age-related cataracts(ARC)were select-ed and divided into three groups:cortical type(ARCC group),nuclear type(ARNC group),and posterior subcapsular type(ARPC group),with 10 cases in each group.Additionally,10 eyes from 10 age-matched patients diagnosed with epiretinal membrane and having clear lenses were selected as the control group.Western blot was used to detect the ex-pression levels of DCLRE1A protein in the anterior capsule tissues of patients in each group and in the lens epithelial cell line(SRA01/04)treated with hydrogen peroxide(H2O2)in vitro and overexpressed DCLRE1A model(OE-DCLRE1A group).The effects of overexpressed DCLRE1A on the expression levels of mitochondrial transcription factor(TFAM)and peroxisome proliferator-activated receptor-γ coactivator-1α(PGC1α)proteins were also detected.Normal cultured SRA01/04 cells were randomly divided into Control group(untreated),H2 O2 group,H2 O2+HA group(transfected with control plasmid HA),and H2O2+OE-DCLRE1A group(transfected with DCLRE1A plasmid).RT-PCR was used to measure mtD-NA expression in each group cells.Changes in mitochondrial membrane potential(MMP)and mitochondrial reactive oxy-gen species(ROS)in each group were detected by immunofluorescence staining.Results Western blot analysis showed that compared with the control group cells,the relative expression levels of DCLRE1A protein in the anterior capsule tis-sues of patients in the ARCC,ARNC,and ARPC groups were all decreased,with statistically significant differences(all P<0.001).In the in vitro H2O2-induced oxidative damage model,compared with the Control group,the relative expression level of DCLRE1A protein in the H2O2 group was significantly decreased(P<0.001).The overexpression efficiency results of DCLRE1A showed that,compared with the Control group,the relative expression level of DCLRE1A protein in the OE-DCLRE1A group cells was significantly increased,with statistical significance(P<0.001).RT-PCR results showed that compared with the H2O2+HA group,the expression level of mtDNA in the H2O2+OE-DCLRE1A group was significantly in-creased(P<0.001).Western blot analysis showed that compared with the H2O2+HA group,the relative expression levels of TFAM and PGC1α proteins in the H2O2+OE-DCLRE1A group were significantly increased(P<0.001).Immunofluores-cence staining results showed that compared with the H2O2+HA group,the MMP level in the H2O2+OE-DCLRE1A group was significantly restored,and the accumulation of mitochondrial ROS was reduced(P<0.001).Conclusion Under H2O2-induced oxidative stress conditions,DCLRE1A promotes the repair of damaged mtDNA in LECs by regulating mito-chondrial biogenesis,thereby reducing LEC apoptosis and participating in the occurrence and development of ARC.
6.Investigating the mechanism of Luteolin in alleviating inflammatory senes-cence in ARPE-19 cells via SIRT1/NF-κB/NLRP3 pathway
Shuyan ZHANG ; Yun XIE ; Yinjian ZHANG
Recent Advances in Ophthalmology 2025;45(9):684-690
Objective To investigate the mechanism of luteolin(LUT)in inhibiting inflammatory aging for treating diabetic retinopathy(DR).Methods Through preliminary experiments,high glucose(HG)and LUT concentrations were established to induce ARPE-19 cells for the experiment.Cells were divided into:Control group(5.5 mmol·L-1 glu-cose),HG group(35 mmol·L-1 glucose),HG+low LUT group(35 mmol·L-1 glucose+20 μmol·L-1 LUT),HG+high LUT group(35 mmol·L-1 glucose+40 μmol·L-1 LUT).Cell viability was measured by CCK-8 assay;Cell migration abil-ity was assessed by scratch assay;ELISA detected inflammatory aging factors[senescence-associated β-galactosidase(SA-β-Gal),interleukin(IL)-1β,IL-6];DCFDA measured intracellular ROS levels;β-galactosidase activity staining identi-fied cellular senescence;TUNEL assay determined apoptosis rate;Western blot and RT-PCR analyzed protein and mRNA expression of silent information regulator 1(SIRT1),nuclear factor(NF)-κB,NOD-like receptor family pyrin domain con-taining 3(NLRP3),and Thioredoxin.Results Compared with the Control group,the cell viability and migration ability of the HG group decreased,and the difference was statistically significant(both P<0.01);Compared with the HG group,both the HG+low LUT group and the HG+high LUT group showed an increase in cell viability and migration ability,and the differences were statistically significant(both P<0.05).Compared with the Control group,the expression levels of SA-β-Gal,IL-1 β,and IL-6 in HG group cells were all increased,and the differences were statistically significant(all P<0.01);Compared with the HG group,the expression levels of SA-β-Gal in the HG+low LUT group and SA-β-Gal,IL-1β,and IL-6 in the HG+high LUT group decreased,and the differences were statistically significant(all P<0.05).Compared with the Control group,the HG group showed an increase in the number of senescent cells,apoptosis rate,and ROS content in the cells,with statistically significant differences(all P<0.01);Compared with the HG group,the number of senescent cells,apoptosis rate,and ROS content in the HG+low LUT group and HG+high LUT group were all reduced,and the differences were statistically significant(all P<0.05).Compared with the Control group,the expression levels of SIRT1 protein and mRNA in HG group cells decreased,while the expression levels of NF-κB,NLRP3,and Thioredoxin protein and mRNA in-creased,and the differences were statistically significant(all P<0.01);Compared with the HG group,the expression lev-els of SIRT1 protein and mRNA in the HG+low LUT group and HG+high LUT group increased,while the expression levels of NF-κB,NLRP3,and Thioredoxin protein and mRNA decreased,and the differences were statistically significant(all P<0.05).Conclusion LUT improves cell viability,migration,senescence and apoptosis levels induced by HG while sup-pressing the expression of inflammatory aging factors,which may be related to its regulation of the SIRT1/NF-κB/NLRP3 signaling pathway.
7.Research on the mechanism of cytochrome P4502C regulating ferroptosis in hu-man retinal microvascular endothelial cells under high-glucose conditions through the GPX4/ACSL4 axis
Ting LUO ; Yan LI ; Like XIE ; Hongbin LÜ
Recent Advances in Ophthalmology 2025;45(9):691-695
Objective To explore the molecular mechanisms by which cytochrome P4502C regulates ferroptosis in hu-man retinal microvascular endothelial cells(hRMECs)under high-glucose conditions.Methods Human retinal microvas-cular endothelial cells(hRMECs)were cultured in vitro and divided into six groups:the NG group(cells cultured in ser-um-free DMEM medium containing 5.5 mmol·L-1 glucose);the NG+fenofibrate group(10 μmol·L-1 fenofibrate added to the NG group);the NG+rifampicin group(10 μmol·L-1 rifampicin added to the NG group);the HG group(cells cul-tured in serum-free DMEM medium containing 25.5 mmol·L-1 glucose);the HG+fenofibrate group(10 μmol·L-1 feno-fibrate added to the HG group);and the HG+rifampicin group(10 μmol·L-1 rifampicin added to the HG group).After 48 hours of culture,subsequent experiments were conducted.Cell viability was assessed using the CCK-8 assay.The levels of malondialdehyde(MDA)and iron content in hRMECs were measured using commercial assay kits.The relative fluores-cence intensity of Liperfluo was quantified by flow cytometry.The mRNA expression levels of glutathione peroxidase 4(GPX4),cytochrome P4502C,and acyl-CoA synthetase long-chain family member 4(ACSL4)in hRMECs were analyzed using real-time quantitative PCR.The protein expression levels of GPX4,cytochrome P4502C,and ACSL4 in hRMECs were evaluated using Western blot analysis.Results Optimal concentration analysis showed that the 10 μmnol·L-1 fenofibrate group had the highest cell viability compared to the HG group(P<0.05),while the 10 μmol·L-1 rifampicin group had the lowest cell viability(P<0.05).Thus,10 μmol·L-1 was selected as the optimal concentration for both fenofibrate and rif-ampicin for subsequent experiments.Cell viability in the NG,NG+fenofibrate,NG+rifampicin,HG,HG+fenofibrate,and HG+rifampicin groups was(100.00±7.85)%,(102.15±9.07)%,(69.97±4.22)%,(61.74±6.13)%,(83.64±7.58)%,and(56.96±5.34)%,respectively.Compared with the NG group,the HG group had significantly lower cell via-bility(P<0.05).Compared with the HG group,the HG+fenofibrate group had significantly higher cell viability(P<0.05).Compared with the NG group,the HG group had higher levels of MDA,iron content,and Liperfluo relative fluores-cence intensity(all P<0.05).Compared with the HG group,the HG+fenofibrate group had lower levels of MDA,iron content,and Liperfluo relative fluorescence intensity(all P<0.05);the HG+rifampicin group had higher levels of these parameters(all P<0.05).Compared with the NG group,the HG group had higher mRNA and protein expression levels of cytochrome P4502C and ACSL4,but lower levels of GPX4 mRNA and protein(all P<0.05).Compared with the HG group,the HG+fenofibrate group had lower mRNA and protein expression levels of cytochrome P4502C and ACSL4,but higher lev-els of GPX4 mRNA and protein(all P<0.05);the HG+rifampicin group had higher mRNA and protein expression levels of cytochrome P4502C and ACSL4,but lower levels of GPX4 mRNA and protein(all P<0.05).Conclusion Cytochrome P4502C can promote ferroptosis of hRMECs under high-glucose conditions by regulating the GPX4/ACSL4 signaling axis;in-hibition of cytochrome P4502C expression can exert a protective effect on DR;modulation of the expression levels or bal-ance of the key factors GPX4 and ACSL4 in this pathway may hold promise as a potential strategy to slow the progression of DR.
8.A study on the impact of tyrosinase on retinal and choroidal changes during refractive development
Kailei WANG ; Xiaoran ZHANG ; Jiaqi MU ; Yamin CHEN ; Panpan LÜ ; Guoge HAN ; Rui HAO
Recent Advances in Ophthalmology 2025;45(9):696-702
Objective To analyze the effects of tyrosinase on choroidal and retinal thickness and blood flow changes in guinea pigs,and to explore the role of tyrosinase in the development and progression of myopia.Methods A total of 30 three-week-old male tri-colored guinea pigs and 10 albino guinea pigs were selected and divided into four groups:control group(tri-colored hyperopic guinea pigs,with no intervention),albino group(albino myopic guinea pigs,with no inter-vention),myopia group(tri-colored myopic guinea pigs,with no intervention),and injection group[tri-colored hyperopic guinea pigs,injected with tyrosinase inhibitor(6 250 μg·L-1),100 μL per day].The experiment lasted for 4 weeks.The refractive status and axial length(AL)of the guinea pigs in each group were measured,along with ocular biometric param-eters related to axial length[anterior chamber depth,aqueous humor depth(AQD),central corneal thickness,lens diame-ter,vitreous chamber depth(VCD)].Optical coherence tomography was used to measure the retinal thickness,choroidal thickness(ChT),and choroidal blood perfusion(ChBP)in different regions of the guinea pigs.The tyrosinase activity in the vitreous and retina of guinea pigs in each group was measured.The expression levels of neurotransmitters in the vitre-ous and retina of guinea pigs in each group were detected.Results The differences in refractive status between the albi-no group and the control group at 0,2,and 4 weeks of the experiment were statistically significant(F=8.972,P<0.05).At the 4th week of the experiment,the refractive status of the injection group was lower than that of the control group,and the AL was greater than that of the control group,with statistically significant differences(both P<0.05).Further analysis of AL-related biometric parameters revealed that only AQD and VCD were associated with the changes in AL of guinea pigs in each group.At the 0th week of the experiment,the average retinal thickness of the control group was greater than that of the albino group,with a statistically significant difference(t=-9.007,P<0.000 1).Moreover,the differences in reti-nal thickness in the outer retina across different directions and time points were statistically significant(all P<0.05).The differences in retinal thickness between the control and albino groups were mainly concentrated in the outer retina.The ChT of the albino group was less than that of the control group,with a significant difference between groups(F=4.809,P=0.030).The ChBP of the control group was significantly higher than that of the albino group at 0,2,and 4 weeks of the experiment(all P<0.05).At the 4th week of the experiment,the tyrosinase activity in the vitreous of the injection,albi-no,and myopia groups was lower than that of the control group,with statistically significant differences(all P<0.05).The differences in neurotransmitters between the albino and control groups were mainly concentrated in the vitreous.In the retina,the ornithine level in the myopia group was higher than that in the albino and control groups,and the tryptophan levels in the myopia and control groups were higher than that in the albino group,with statistically significant differences(all P<0.05).Conclusion Tyrosinase plays a crucial role in the development of myopia,regulating the development of refractive status by influencing the physiological properties of the retina and choroid.
9.The impact of LncRNA NEAT1 on lens epithelial cell injury under high-glu-cose conditions by modulating the miR-204-5p/TET1 axis
Yi LU ; Fan CHEN ; Huiling YE ; Longqi QIAN
Recent Advances in Ophthalmology 2025;45(9):703-710
Objective To investigate the effects of LncRNA NEAT1-regulated miR-204-5p/ten-eleven translocation protein 1(TET1)on lens epithelial cell(LEC)injury under high-glucose conditions.Methods Target validation was per-formed through RNA pull-down,RNA immunoprecipitation,and dual-luciferase reporter assays.HLEB3 cells were random-ly divided into normal control,high-glucose,si-NEAT1,si-NC+NC-miR-204-5p,and si-NEAT1+miR-204-5p inhibitor groups.Except for the normal control group,all other groups were induced with high glucose.After lentiviral plasmid transfection,RT-qPCR and Western blot were used to detect the expression of LncRNA NEAT1,miR-204-5p,and TET1 in each group of HLEB3 cells.Cell viability and apoptosis were detected by CCK-8 and flow cytometry assays,respectively.Western blot was used to detect the expression of apoptosis-and epithelial-mesenchymal transition(EMT)-related pro-teins.The activity of cellular antioxidant enzymes,reactive oxygen species(ROS),and levels of inflammation-related fac-tors were measured.SD rats were randomly divided into control,diabetic cataract(DC),NEAT1 knockdown,negative control,and NEAT 1 knockdown+miR-204-5p inhibitor groups.DC rat models were induced by intraperitoneal injection of streptozotocin.After lentiviral plasmid intervention,the expression of LncRNA NEAT1,miR-204-5p,and TET1 in rat lens tissues was detected.Lens opacity was scored,and the morphology of rat lens tissues was examined by HE staining.Results LncRNA NEAT1 can target the regulation of miR-204-5p/TET1.Compared with the normal control group,the relative expression of LncRNA NEAT1,TET1 protein,TET1 mRNA,and the proteins Caspase-3,Cleaved Caspase-3,Bax,N-cadherin,MMP9,and MMP2,as well as the levels of ROS,IL-1β,and IL-6,were increased in the high glucose group,while the relative expression of miR-204-5p,cell viability,and the relative expression of Bcl-2 and E-cadherin proteins,and the activities of SOD,CAT,and GSH-Px were decreased(all P<0.05).Compared with the high glucose group,the above mentioned indicators in HLEB3 cells of the si-NEAT1 group were reversed(all P<0.05).Compared with the si-NEAT1 group,the relative expression of TET1 protein,TET1 mRNA,and the proteins Caspase-3,Cleaved Caspase-3,Bax,N-cad-herin,MMP9,and MMP2,as well as the levels of ROS,IL-1β,and IL-6,were increased in the si-NEAT1+miR-204-5p in-hibitor group of HLEB3 cells,while the relative expression of miR-204-5p,cell viability,and the relative expression of Bcl-2 and E-cadherin proteins,and the activities of SOD,CAT,and GSH-Px were decreased(all P<0.05).Compared with the control group,the relative expression of LncRNA NEAT1 and TET1 protein and mRNA,and the lens opacity score were in-creased in the DC group of rats,while the relative expression of miR-204-5p was decreased(all P<0.05).Compared with the DC group,the above mentioned indicators were reversed in the NEAT1 knockdown group(all P<0.05).Compared with the NEAT1 knockdown group,the relative expression of TET1 protein and mRNA and the lens opacity score were in-creased in the NEAT1 knockdown+miR-204-5p inhibitor group of rats,while the relative expression of miR-204-5p was de-creased(all P<0.05).Conclusion Knockdown of LncRNA NEAT1 can alleviate LEC injury under high-glucose condi-tions and mitigate lens opacity and tissue injury in DC rats by up-regulating miR-204-5p to reduce TET1 expression.
10.Correlation of changes in inner retinal irregularity index after idiopathic macular epiretinal membrane stripping with visual function
Xiaobo ZHU ; Yan SU ; Xiaoling YAN ; Shuo ZHAO ; Wenbin WEI
Recent Advances in Ophthalmology 2025;45(9):711-714
Objective To investigate the correlation between changes in the inner retinal irregularity index(IRII)af-ter macular epiretinal membrane(ERM)stripping and visual function in patients with idiopathic macular epiretinal mem-brane(IMEM).Methods A retrospective analysis was conducted on the clinical data of 134 patients(162 eyes)with IMEM who visited our hospital from March 2022 to December 2024.Based on fundus color photography and OCT findings,the patients were divided into the cellophane macular reflex(CMR)group and the preretinal macular fibrosis(PMF)group.Differences in central macular thickness(CMT),best-corrected visual acuity(BCVA),inner retinal thickness(IRT),and IRII were analyzed between the two groups.The diagnostic efficacy of these indicators for IMEM at admission was analyzed using receiver operating characteristic(ROC)curves.The differences in visual function indicators and IRII before and 3 months after ERM stripping were compared in IMEM patients.The correlation between IRII levels and visual function parameters at 3 months postoperatively was analyzed using Pearson correlation analysis.Results Among the 134 patients(162 eyes)with IMEM,93 patients(103 eyes)were in the CMR group and 41 patients(59 eyes)were in the PMF group.The CMT,IRT,and IRII were significantly lower in the CMR group than in the PMF group(all P<0.05).The areas under the curve(AUC)for CMT,IRT,and IRII were 0.616,0.609,and 0.862,respectively(all P<0.05).Among the 134 patients(162 eyes)with IMEM,79 patients(86 eyes,53.86%)underwent surgical treatment,and 55 patients(76 eyes,46.91%)received non-surgical treatment.Three months after surgery,the CMT,IRT,and IRII in IMEM patients were sig-nificantly lower than those before surgery(all P<0.05).At 3 months postoperatively,CMT and IRT were significantly pos-itively correlated with IRII in IMEM patients(all P<0.05).Conclusion CMT,IRT,and IRII all have good diagnostic ef-ficacy for IMEM staging.Moreover,IRII changes in IMEM patients who underwent macular ERM stripping are positively correlated with visual function.

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