1.Research progress on the role of advanced glycosylation end products in ocular diseases
Xiaoqi GONG ; Jiaojiao FENG ; Yibo HAN ; Jike SONG ; Hongsheng BI
International Eye Science 2025;25(6):906-911
The excessive accumulation of advanced glycosylation end products(AGEs), the end products of non-enzymatic glycosylation reactions, can be involved in the pathological processes of various ocular diseases through mechanisms such as oxidative stress, inflammatory responses and apoptosis. In this paper, we systematically reviewed the key role of AGEs in diabetic keratopathy, cataract, glaucoma, age-related macular degeneration(ARMD)and diabetic retinopathy(DR). It was found that AGEs activate signalling pathways such as NADPH oxidase, MAPK and NF-κB by binding to the receptor RAGE, leading to reactive oxygen species(ROS)generation, release of inflammatory factors, and vascular endothelial dysfunction, which in turn induces delayed corneal healing, cross-linking of lens proteins, optic nerve degeneration, formation of choroidal neovascularisation(CNV), and blood-retinal barrier(BRB)disruption. For example, in diabetic keratopathy, AGEs delay wound healing via the ROS/NLRP3 inflammatory vesicle axis; in cataract, ascorbic acid-mediated cross-linking of lens proteins due to AGEs directly impairs lens transparency; and in DR, AGEs exacerbate microvascular damage by regulating vasucular endothelial growth factor(VEGF)expression and pericyte apoptosis. In addition, this article discusses the advances and limitations of AGEs detection techniques, such as the potential application of lens AGEscan fluorescence assay in screening for diabetic complications, and the need to develop tissue-specific assays for aqueous humour and vitreous. For therapeutic strategies, the research directions of inhibiting AGEs production, blocking RAGE signalling pathway and developing anti-glycosylation drugs are proposed to emphasise their clinical value in delaying disease progression. This review not only integrates the molecular mechanisms and clinical associations of AGEs in ocular diseases, but also provides a theoretical basis for targeted interventions, which is of great significance in exploring novel diagnostic and therapeutic strategies.
2.Distribution of pupil diameter and its association with myopia in school age children
Chinese Journal of School Health 2025;46(8):1194-1197
Objective:
To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia.
Methods:
Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia.
Results:
The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34, P trend < 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P <0.01).
Conclusions
Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.
3.Effect of electroacupuncture at the Taiyang acupoint on refractive parameters and the expression of β-catenin and integrin β1 in ciliary body in mice with form-deprivation myopia
Lu CHEN ; Yue TENG ; Wenjun JIANG ; Hongsheng BI
International Eye Science 2025;25(11):1735-1739
AIM:To investigate the effects of electroacupuncture at the Taiyang on refractive parameters and the expression of β-catenin and integrin β1 in the ciliary body of mice with form-deprivation myopia(FDM).METHODS:A total of 48 3-week-old healthy C57BL/6J mice were randomly divided into 4 groups: normal control(NC), FDM group, sham acupuncture(sham), and electroacupuncture at Taiyang acupoint(Taiyang), with 12 mice in each group. Mice in the FDM, sham, and Taiyang groups, wore translucent custom-made eye masks on the right eye to induce myopia. The Taiyang group received electroacupuncture stimulation at the Taiyang acupoint, while the sham group underwent non-penetrating stimulation with a blunt wooden stick. No intervention was performed on the NC group. Refraction and axial length were measured by infrared autorefractor and optical coherence tomography(OCT)before modeling and at 4 wk after modeling. The expression levels of β-catenin and integrin β1 in the ciliary body of mice at 4 wk after modeling were detected using quantitative real-time PCR(qPCR)and Western blotting(WB).RESULTS:After modeling for 4 wk, compared with the NC group, the FDM and sham groups showed significantly decreased refractive power(both P<0.05), elongated axial length(both P<0.05), and increased β-catenin and integrin β1 expression. Compared with the FDM and sham groups, the Taiyang group showed significantly increased refractive power(both P<0.05), shortened axial length(both P<0.05), and decreased β-catenin and integrin β1 expression.CONCLUSION:Electroacupuncture stimulation at the Taiyang acupoint effectively delayed the progression of myopia in FDM mice, and this effect may be partially mediated through modulating the expression of β-catenin and integrin β1 in the ciliary body.
4.Innovative design and research progress of liposomes in ocular drug delivery
Xiaoyun DONG ; Jike SONG ; Hongsheng BI
International Eye Science 2025;25(11):1777-1784
The complex anatomical structure and physiological barriers of the eye present substantial challenges for local drug delivery, leading to suboptimal ocular drug bioavailability, which typically remains below 5% in conventional ophthalmic formulations. Frequent or high-dose administration not only increases the treatment burden but also heightens the risk of both local and systemic adverse effects. Liposomes, as an advanced drug delivery system, enhance ocular bioavailability through their biocompatibility and targeted delivery properties. Recent innovations in surface modification and functionalization have further enhanced their ability to overcome ocular barriers and facilitate controlled drug release. Liposome-based formulations have demonstrated significant therapeutic potential for diseases such as glaucoma and dry eye syndrome. Drawing on the research advancements over the past 5 a, this article systematically reviews the innovative design strategies and applications of liposomes in ocular drug delivery, with the aim of providing theoretical basis and technical reference for the development of new ophthalmic drugs.
5.Advances in the relationship between insulin-like growth factor-1 and eye diseases
Yue TENG ; Hongsheng BI ; Wenjun JIANG
International Eye Science 2025;25(11):1826-1832
Insulin-like growth factor-1(IGF-1)is a multifunctional growth factor which plays an important role in various physiological and pathological processes of the body by regulating biological behaviors such as cell proliferation, differentiation, and migration. Studies have found that abnormal expression of IGF-1 in the retina, sclera and other eye tissues can participate in the occurrence, development and prognosis of various ophthalmic diseases by regulating retinal autophagy flux and angiogenesis, adipogenic differentiation of orbital soft tissues and degradation of scleral extracellular matrix. This paper systematically integrates the expression level changes and mechanism of action of IGF-1 in ophthalmic diseases such as diabetic retinopathy(DR), age-related macular degeneration(ARMD), retinopathy of prematurity(ROP), Graves' ophthalmopathy, myopia, corneal injury and uveal melanoma(UM), and combines the latest clinical and animal experimental evidence to evaluate the bright prospects and potential risks of IGF-1 targeted therapy, in order to provide new ideas and theoretical basis for the prevention and treatment of ophthalmic diseases.
6.Current status of research on the correlation between gut microbes and oph-thalmic diseases
Wenhui LI ; Yuhui ZHAO ; Hongsheng BI ; Qingmei TIAN ; Xiaofeng XIE
Recent Advances in Ophthalmology 2024;44(5):401-404
Trillions of microbes inhabit the human intestinal tract as a complex ecological community.They impact the host's normal physiological activities and disease susceptibility through their collective metabolic activities and interactions with the host.Gut microbes participate in immune regulation and nutrient metabolism and are closely related to aging.In recent years,the role of gut microbes in ophthalmic diseases has received much attention.This paper reviews the relation-ship between gut microbes and various ophthalmic diseases,aiming to provide new insights into the diagnosis and treatment of ophthalmic diseases.
7.Effect of intravitreal injection of fibrillin-2(FBN2)recombinant protein on FBN2-deficient retinopathy
Ruixue ZHANG ; Wenjun JIANG ; Dadong GUO ; Yongwei SHI ; Hongsheng BI ; Ying WEN
Recent Advances in Ophthalmology 2024;44(6):428-432
Objective To investigate the effect of intravitreal injection of fibrillin-2(FBN2)recombinant protein on FBN2-deficient retinopathy.Methods Thirty-two SPF-grade C57BL/6J mice were randomly divided into 4 groups:nor-mal control group,negative control group,FBN2 knockdown group,and FBN2 recombinant protein group,with 8 mice in each group.The right eyes were taken as the experimental eyes.Mice in the normal control group did not receive any inter-vention,mice in the negative control group were intravitreally injected with 3 μL empty vector(1 mg·L-1),and mice in the FBN2 knockdown group and FBN2 recombinant protein group were intravitreally injected with 3 μL adeno-associated vi-rus(1 mg·L-1).After 4 weeks,mice in the FBN2 recombinant protein group were intravitreally injected with 3 μL FBN2 recombinant protein(1 mg·L-1).Then,electroretinogram(ERG)and optical coherence tomography(OCT)were used to measure the amplitude of Rod-b and Max-a waves and the changes in the retinal structure.Real-time quantitative poly-merase chain reaction(RT-PCR)and Western blot were used to detect changes in FBN2,microfibril-associated glycopro-tein 2(MAGP-2),collagen I(COL1)mRNA and protein expression in the mouse retina.Results The ERG findings showed that compared with the negative control group and normal control group,the amplitude of Rod-b and Max-a waves in the retina of mice in the FBN2 knockdown group and FBN2 recombinant protein group decreased(all P<0.05);com-pared with the FBN2 knockdown group,the amplitude of Rod-b and Max-a waves in the retina of mice in the FBN2 recom-binant protein group significantly increased(both P<0.05).The OCT findings showed that compared with the FBN2 knock-down group,the structure of the retinal pigment epithelium and the light reflex in the FBN2 recombinant protein group be-came more regular.The RT-PCR detection results showed that compared with the FBN2 knockdown group,the expression of FBN2 mRNA in the retinal tissue of mice in the FBN2 recombinant protein group significantly increased,while the ex-pression of COL1 and MAGP-2 mRNA significantly decreased(all P<0.05).Western blot assay results showed that com-pared with the FBN2 knockdown group,the expression of FBN2 protein in the retinal tissue of mice in the FBN2 recombi-nant protein group increased significantly,while the expression of COL1 and MAGP-2 proteins decreased significantly(all P<0.05).Conclusion Intravitreal injection of FBN2 recombinant protein can compensate for the endogenous deficiency of FBN2 in mice with FBN2-deficient retinopathy and achieve therapeutic effects by regulating COL1 and MAGP-2 expres-sion.
8.Analysis of corneal biomechanical changes after femtosecond laser-assisted in situ keratomileusis combined with accelerated corneal cross-linking for cor-rection of high myopia based on Corvis ST
Qingbao WANG ; Hongsheng BI ; Hua FAN ; Peipei ZU ; Li LI ; Peng JI
Recent Advances in Ophthalmology 2024;44(8):632-636
Objective To evaluate the corneal biomechanical changes after femtosecond laser-assisted in situ kerato-mileusis(FS-LASIK)combined with accelerated corneal cross-linking(FS-LASIK Xtra)for the correction of high myopia u-sing Corvis ST.Methods In this prospective case-control study,185 patients(185 eyes)who underwent surgical correc-tion of high myopia in the Affiliated Eye Hospital of Shandong University of Chinese Medicine from July 2020 to July 2022 were selected,including 93 patients receiving FS-LASIK Xtra in the FS-LASIK Xtra group and 92 patients receiving FS-LASIK in the FS-LASIK group.All patients had their right eyes included in the study.During the 6-month follow-up,the uncorrect-ed visual acuity,spherical equivalent(SE),mean corneal curvature,thinnest corneal thickness,corneal biomechanical pa-rameters[deformation amplitude ratio at 2 mm(DAR 2 mm),integrated radius(IR),stiffness parameter at the first appla-nation(SP-A1),stress-strain index(SSI)],and changes in corneal biomechanical parameters before and after surgery(difference between 6 months after surgery and before surgery,namely ΔDAR 2 mm,ΔIR,ΔSP-A1,and ΔSSI)were recor-ded.Independent sample t test and Mann-Whitney U test were used to compare the data between groups.Results Three months after surgery,the SE in the FS-LASIK group and the FS-LASIK Xtra group was(-0.21±0.31)D and(-0.04±0.36)D,respectively,and the difference was statistically significant(t=3.49,P=0.001).Six months after surgery,the SE in the FS-LASIK group and the FS-LASIK Xtra group was(-0.33±0.31)D and(-0.14±0.37)D,respectively,and the difference was statistically significant(t=4.00,P<0.001).There was no significant difference in efficacy index and safety index between the FS-LASIK group and the FS-LASIK Xtra group at 6 months after operation(both P>0.05).There were no significant differences in DAR 2 mm,IR,SP-A1,SSI and other biomechanical parameters between the two groups before surgery(all P>0.05).At 6 months postoperatively,ΔIR in the FS-LASIK group and the FS-LASIK Xtra group was 3.03±0.78 and 2.67±0.80,respectively;ΔSP-A1 was-35.93±12.04 and-30.43±12.44,respectively;and ΔSSI was-0.09±0.10 and-0.03±0.06,respectively.The differences between the two groups were all statistically significant(all P<0.05).Conclusion FS-LASIK Xtra for correction of high myopia improves the stability of postoperative visual acuity and SE with good safety and efficacy,but reduces the stability of comeal biomechanical parameters compared with before surgery;still,it is better than conventional FS-LASIK,and the long-term effect needs to be further assessed.
9.Progress of research on the involvement of neurotransmitters in the develop-ment of myopia
Xinyue CHEN ; Ping ZHAO ; Yuecong SUN ; Bin GUO ; Hongsheng BI
Recent Advances in Ophthalmology 2024;44(8):653-657
Myopia is the most common refractive error,which seriously damages the visual health of adolescents.The current research on the pathogenesis of myopia mainly focuses on genetics,visual environment,biochemical mechanism and so on.Neurotransmitters,as important mediators of refractive development,form complex regulatory networks and participate in molecular synthesis and metabolic activities related to myopia.Intraocular neurotransmitters affect scleral re-modeling by regulating the growth of retinal pigment epithelium and the thickness of choroid and play an important role in the occurrence and development of myopia.This paper reviews the role of cholines,amines,amino acids,peptides and other neurotransmitters in the pathogenesis of myopia,providing new ideas for the prevention and control of myopia.
10.Fibrillin-2 interfering induced retinopathy and its possible mechanism
Ruixue ZHANG ; Wenjun JIANG ; Dadong GUO ; Yongwei SHI ; Hongsheng BI ; Ying WEN
Chinese Journal of Experimental Ophthalmology 2024;42(9):798-805
Objective:To investigate the expression of latent transforming growth factor-β-binding protein (LTBP), transforming growth factor-β (TGF-β), cyclin-dependent kinase 2 (CDK2) and cyclin D2 (CCND2) in fibrillin-2 ( FBN2) interfering induced mouse retinopathy. Methods:Twenty-seven 8-week-old C57BL/6J mice were randomly divided into normal control group, empty vector group and FBN2 interference group according to the random number table method, with 9 mice in each group.The normal control group was not treated.The empty vector group and FBN2 interference group were intravitreally injected with 3 μl empty vector and 3 μl adeno-associated virus (AAV) carrying the sh-FBN2 interference plasmid in the right eye, respectively.The structural and functional changes of the retina were detected at 4 weeks after injection by optical coherence tomography (OCT) and full-field electroretinography (ERG).The expression and distribution of FBN2 protein in the retina were detected by immunofluorescence staining.The mRNA and protein expression levels of FBN2, LTBP-1, TGF-β2, CDK2 and CCND2 in mouse retina were detected by real-time fluorescence quantitative PCR and Western blot.All experiments complied with the ARVO statement.The research scheme was approved by the Experimental Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (No.2019036).Results:Four weeks after injection, the results of OCT examination showed that compared with normal control and empty vector groups, the retinal pigment cortex of the FBN2 interference group was irregular with high density reflection areas.Full-field ERG results showed that compared with normal control and empty vector groups, the amplitude of Rod-a, Rod-b, Max-a and Max-b waveforms in FBN2 interference group decreased, and the differences were statistically significant (all at P<0.05).The results of immunofluorescence staining showed that FBN2 was expressed in the whole retina, and the fluorescence intensity of FBN2 was weaker in FBN2 interference group than that in normal control and empty vector groups.The fluorescence intensity of FBN2 in normal control group, empty vector group and FBN2 interference group was 16.21±2.21, 15.57±3.63 and 5.32±1.06, respectively, with a statistically significant overall difference ( F=66.03, P<0.05).The fluorescence intensity of FBN2 protein in FBN2 interference group was significantly lower than that in empty carrier group and normal control group (both at P<0.05).Compared with normal control and empty vector groups, the relative expression levels of LTBP-1 and TGF-β2 mRNA and protein were significantly increased in FBN2 interference group, while the relative expression levels of FBN2, CDK2 and CCND2 mRNA and protein were significantly decreased, and the differences were statistically significant (all at P<0.05). Conclusions:The increase of LTBP-1 and TGF-β2 and the decrease of G1/S phase related proteins CDK2 and CCND2 are involved in the development of FBN2-deficient retinopathy.


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