EXPERIMENTAL EYE RESEARCH
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2025
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IF 2.7
Xiangyu Liu,Meiyu Wang,Zhenzhen Ji,Xuanlin Zhu,Jinchang Tian,Yingxin Chen,Jun Cai,Mei Dong,Zhijian Li
Cataracts are one of the primary causes of blindness worldwide; however, their pathogenesis remains unclear. Oxidative stress and apoptosis are two dominant inducers in the progression of cataracts; however, little is known about the specific mechanisms associated with mitophagy. This study aimed to investigate the role of PTEN-induced putative kinase 1(PINK1)-mediated mitophagy in cataract development. Initially, we induced a rat cataract model using sodium selenite and observed the upregulated expression of PINK1 and other autophagy-related proteins within lens epithelial cells, accompanied by apoptosis. Furthermore, the survival rate of human lens epithelial cells was significantly reduced by H 2 O 2 treatment. However, PINK1 overexpression reduced ROS levels, allowing cells to survive. This reduction in reactive oxygen species (ROS) levels led to a decrease in cleaved caspase-3 and Bcl-2-associated X protein (Bax) expression and an increase in B-cell lymphoma 2 (Bcl-2) levels. In summary, PINK1 maintains mitochondrial functional stability and inhibits apoptosis by activating mitophagy, thus potentially playing a crucial protective role in cataract pathogenesis.
研究领域:
细胞生物学
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医学
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DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
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2023
·Vol. 64
·期 3
·16-16
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IF 4.4
Lili Lian,Zhenmin Le,Zhenzhen Wang,Ying-ao Chen,Xiaodong Jiao,Hang Qi,J. Fielding Hejtmancik,Xiaoyin Ma,Qinxiang Zheng,Yueping Ren
Purpose:To determine whether SIRT1 regulates high glucose (HG)–induced inflammation and cataract formation through modulating TXNIP/NLRP3 inflammasome activation in human lens epithelial cells (HLECs) and rat lenses.Methods:HG stress from 25 to 150 mM was imposed on HLECs, with treatments using small interfering RNAs (siRNAs) targeting NLRP3, TXNIP, and SIRT1, as well as a lentiviral vector (LV) for SIRT1. Rat lenses were cultivated with HG media, with or without the addition of NLRP3 inhibitor MCC950 or SIRT1 agonist SRT1720. High mannitol groups were applied as the osmotic controls. Real-time PCR, Western blots, and immunofluorescent staining evaluated the mRNA and protein levels of SIRT1, TXNIP, NLRP3, ASC, and IL-1β. Reactive oxygen species (ROS) generation, cell viability, and death were also assessed.Results:HG stress induced a decline in SIRT1 expression and caused TXNIP/NLRP3 inflammasome activation in a concentration-dependent manner in HLECs, which was not observed in the high mannitol–treated groups. Knocking down NLRP3 or TXNIP inhibited NLRP3 inflammasome-induced IL-1β p17 secretion under HG stress. Transfections of si-SIRT1 and LV-SIRT1 exerted inverse effects on NLRP3 inflammasome activation, suggesting that SIRT1 acts as an upstream regulator of TXNIP/NLRP3 activity. HG stress induced lens opacity and cataract formation in cultivated rat lenses, which was prevented by MCC950 or SRT1720 treatment, with concomitant reductions in ROS production and TXNIP/NLRP3/IL-1β expression levels.Conclusions:The TXNIP/NLRP3 inflammasome pathway promotes HG-induced inflammation and HLEC pyroptosis, which is negatively regulated by SIRT1. This suggests viable strategies for treating diabetic cataract.
研究领域:
眼科学
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细胞生物学
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糖尿病
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炎症
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-22
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IF 12.6
Jiang Luyang,Liu Jinxia,Chen Silong,Cui Wenyu,Guo Jiarui,Cheng Xiaoyu,Zheng Yingying,Yang Wenxin,Pan Zicai,Wang Yao,Zhao Mary,Han Haijie,Yao Ke,Yu Yibo
Oxidative stress, which results from the accumulation of free radicals, plays a substantial role in cataract formation. Antioxidants have shown promise in mitigating or even preventing this process. However, delivering antioxidants noninvasively to the anterior segment of the eye has been a significant challenge. In this study, we developed ceria nanoparticles modified with cyclic cell-penetrating peptides to overcome the obstruction of the dense corneal barrier on topical drug delivery. Our results demonstrated that modified ceria nanoparticles with cell-penetrating peptides (CPPs) facilitate the opening of tight junctions in human corneal epithelial cells. This characteristic considerably enhances the trans-corneal transport of nanoparticles and improves cellular uptake efficiency, while also contributing to their intracellular enrichment toward mitochondria. Further experiments confirmed that the modified ceria nanoparticles effectively counteracted ferroptosis induced by oxidative stress in lens epithelial cells both in vitro and in vivo, substantially reducing cataract formation. The successful development of ceria nanoparticles modified with cyclic cell-penetrating peptides (cCPPs) opens new avenues for research in cataract prevention and treatment. Additionally, the modified ceria nanoparticles could serve as a noninvasive drug delivery system, which holds remarkable potential for advancing drug delivery in diseases affecting the anterior segment of the eye.Graphical
研究领域:
眼科学
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纳米医学
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药理学
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2018
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IF 4.56
Chunjuan Zhang,Tonghua Xu,Donglei Zhang,Wei He,Siling Wang,Tongying Jiang
To improve the corneal permeability and water-solubility of disulfiram (DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF (DSF SD ) by hot melt method. The DSF SD was characterized by DSC, XRD, and IR, and the results suggested that DSF was amorphous in DSF SD . The DSF SD was added to borate buffer solution (BBS) contained 20% poloxamer P407 and 1.2% poloxamer P188 to form in-situ gel. In vitro and in vivo experiments revealed that DSF SD combined with in-situ gel (DSF SD /in-situ gel) increased the residence time and the amount of DSF penetrated through the corneal. The pharmacodynamics studies exhibited DSF SD /in-situ gel delayed the development of selenium-induced cataract at some content. These results investigated that DSF SD /in-situ gel as a drug delivery system can improve DSF ocular permeability.
研究领域:
药剂学
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眼科
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药物传递系统
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产品关联
DOI
PubMed
高影响因子
Photodiagnosis and Photodynamic Therapy
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2024
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IF 3.1
Jian-Feng Zhao,Chen Yang,Jie Zhou,Hai-Yan Zhang,Yu Geng
Purpose To assess the variability and correlation of ocular biometric parameters in eyes with cataracts and examine their association with age and gender. Methods A retrospective analysis was performed on biometric data from 7,458 eyes without retinal pathologies, using an optical biometer equipped with low-coherence reflectometry technology. Pearson's correlation coefficients (r) were used to evaluate the relationships between age, gender, and various ocular parameters, including axial length (AL), anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), corneal refractive power (Km), and white-to-white (WTW) measurement. Results The mean AL was 23.82 ± 1.83 mm (SD). Among the study cohort, 8.0 % (593 eyes) were categorized as having short AL (AL ≤ 22 mm), 60.5 % (4,520 eyes) as having normal AL (22 mm < AL ≤ 24 mm), 21.2 % (1,579 eyes) as having long AL (24 mm < AL ≤ 26 mm), and 10.3 % (766 eyes) as having a AL (> 26 mm). The mean age of the cohort was 64.18 ± 14.95 years (range: 18 - 98 years), with males averaging 56.53 ± 13.88 years and females averaging 72.19 ± 11.41 years. Mean values for ACD, LT, Km, CCT, WTW, and angle kappa were found to vary with both age and gender. Males demonstrated significantly longer AL, deeper ACD, thicker LT, larger WTW, and lower Km compared to females ( P < 0.05). Although males exhibited a greater anterior segment length (ASL), this difference did not reach statistical significance ( P > 0.05). No significant correlation was found between ACD and AL in the short and long AL groups, while a positive correlation was observed in the normal and long AL groups. Additionally, LT demonstrated a negative correlation with AL in the normal AL group but a positive correlation in the long AL group. Conclusions Cataracts develop at a greater age in female patients than in males. Ocular biometric parameters, including ACD, LT, CCT, Km, and (WTW) measurement, are influenced by age and gender. Lens thickness is the primary factor affecting ACD, though CCT, Km, and WTW also play significant roles. Furthermore, a negative correlation between AL and LT was identified, with variations depending on AL classification.
研究领域:
眼科
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生物医学工程
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临床研究
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老年医学
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屈光手术
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DOI
高影响因子
LIFE SCIENCES
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2025
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IF 5.1
Zexuan Li,Xinyue Deng,Yanna Cao,Hongbo Xu,Jiangang Wang,Lamei Yuan,Hao Deng
Aim Congenital cataract, a lenticular opacity diagnosed at birth or early in the postnatal period, often causes visual impairment. The pathogenic mechanisms of various cataract-associated variants are complex and diverse, and current knowledge is insufficient. This study aimed to determine the molecular etiology of congenital nuclear cataract in a Han-Chinese family and to reveal the pathogenic mechanisms of common cataract-associated variants with unclear mechanisms. Methods Genetic analysis including whole exome sequencing and bioinformatics was conducted in the family. Functional analysis was performed to elucidate the changes in protein cellular distribution, degradation, and function induced by the variants. Results A heterozygous c.773C > T transition (p.S258F) in the gap junction protein alpha 8 gene ( GJA8 ), encoding connexin 50 (Cx50), was identified in a family with congenital nuclear cataract. Functional analysis of this variant and two other GJA8 variants with unclear pathogenic mechanisms showed that the Cx50V44M mutant correctly trafficked to the plasma membrane, whereas the Cx50R76C mutant and Cx50S258F mutant exhibited trafficking defects resulting from delayed degradation and accelerated degradation, respectively. All three mutants exhibited increased autophagic activity, while only the Cx50V44M mutant and Cx50S258F mutant underwent autophagy-mediated Cx50 degradation. All mutants failed to form functional hemichannels and gap junction channels. Significance This study identified a heterozygous GJA8 missense variant c.773C > T (p.S258F) responsible for congenital nuclear cataract, and revealed three distinct pathogenic mechanisms of three cataract-associated GJA8 variants, particularly emphasizing dysregulated autophagy involving in aberrant Cx50 degradation.
研究领域:
医学遗传学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
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IF 3.887
Chang Liu,Qi Lan,Wei He,Changlu Nie,Chunjuan Zhang,Tonghua Xu,Tongying Jiang,Siling Wang
The purpose of the study was to design a novel octa-arginine (R8) modified lipid emulsion (LE) system for the ocular delivery of the lipophilic drug disulfiram (DSF). The influence of the particle size of the lipid emulsions and the presence of R8 on corneal permeation was studied. DSF-loaded lipid emulsions with different particle sizes (DSF-LE1, DSF-LE2, DSF-LE3) and DSF-loaded lipid emulsions modified with R8 (DSF-LE1-R8 and DSF-LE2-R8) were prepared. The Zeta potential of the lipid emulsions was changed from negative to a positive value after modification of R8. The mucoadhesion of different preparations was investigated, and DSF-LE1-R8 was found to produce the strongest mucoadhesion. The in vitro corneal penetration study and in vivo ocular distribution study showed that the R8 modified lipid emulsion (DSF-LE1-R8) with a nano particle size, exhibited the highest permeability and the largest amount of DDC distributed in ocular issues. Coumarin-6 labelled LE1-R8 displayed more homogeneous fluorescence with the deeper penetration into the cornea compared with other preparations at various times. Confocal laser scanning microscopy showed that, in addition to paracellular routes, LE-R8 could also transport across the corneal epithelium by transcellular routes as a result of increased uptake due to the R8 modification. Furthermore, the anti-cataract effect was evaluated and it was found that DSF-LE1-R8 exhibited a marked anti-cataract effect. Therefore, the lipid emulsions with nano-sized particles and modification of R8 were proposed as a potential ocular delivery system to improve the corneal penetration and ocular delivery of DSF.
研究领域:
药剂学
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眼科
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Jiahao Wang,Renjie Zhang,Hongying Xie,Yuexin Yang,Hao Chen,Quankui Lin
In cataract, oxidative stress plays an important role. It breaks the balance of the antioxidant defense system by destroying biological macromolecules such as proteins, lipids and nucleic acids in the lens, induces lens opacity, and then leads to the formation of cataract. The antioxidant properties of epigallocatechin gallate (EGCG) are well-established, particularly its ability to scavenge ROS and modulate cellular pathways. However, its therapeutic potential is limited by poor stability and bioavailability. To overcome these challenges, the work is designed to form a metal-phenolic network (MPN) system by coordinating EGCG with zinc ions. MPNs offer distinct advantages for ocular drug delivery, including enhanced structural stability, improved cellular uptake, and the ability to simultaneously target multiple oxidative stress pathways. By doing so, an antioxidant nanoparticle is formed to slow down the turbidity process of the lens induced by oxidative stress and thus prevent the occurrence of cataract. The particle size, zeta potential, ultraviolet absorption spectrum, FTIR, surface morphology and element distribution of EGCG-Zn were determined. In vitro, EGCG-Zn has good biosafety, cell uptake performance and anti-cell damage performance. In addition, from a mechanistic analysis, the particles can scavenge free radicals and reduce the production of intracellular ROS. Similarly, EGCG-Zn can well prevent the damage of reactive oxygen species to intracellular lysosomes, mitochondria, cytoskeleton, DNA synthesis and cell senescence. In the UV-B-induced cataract animal model in rats, EGCG-Zn has good in vivo safety. The transparency of the lens in the experimental group using EGCG-Zn is significantly lower than that in the untreated model group. In conclusion, EGCG-Zn nanoparticles are expected to become an important means in the field of cataract treatment, bringing hope for restoring clear vision to many cataract patients.
研究领域:
眼科
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药剂学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2019
·Vol. 20
·期 2
·1017-1024
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IF 1.851
Duzhen Zhang,Man Li
Puerarin is the major bioactive ingredient isolated from the dry root of Pueraria lobata, a plant used in traditional Chinese medicine. Puerarin has been used to treat diabetes and cataracts in China; however, its underlying mechanism of action remains unclear. The aim of the present study was to investigate the effectiveness and mechanism of puerarin in preventing cataracts in diabetic rats. Diabetes was induced by streptozocin (STZ) administration and rats were intraperitoneally injected with puerarin (25, 50 and 100 mg/kg). Blood glucose levels and cataract development were examined in the different experimental groups. In addition, the expression levels of markers associated with oxidative stress, including nuclear factor erythroid 2 like 2 (Nrf2) and heme oxygenase‑1 (HO‑1), were analyzed. The present results suggested that treatment with puerarin at 25, 50 and 100 mg/kg significantly reduced blood glucose levels and the incidence of cataract in STZ‑induced diabetic rats. Additionally, puerarin treatment reduced oxidative stress, restoring the levels of malondialdehyde and glutathione, and the activity of glutathione peroxidase. Furthermore, puerarin administration decreased the expression levels of retinal vascular endothelial growth factor and interleukin‑1β and increased the mRNA expression levels of Nrf2 and HO‑1, thus inhibiting oxidative stress. The present findings suggested that puerarin had hypoglycemic effects and that it prevented cataract development and progression in diabetic rats by reducing oxidative stress through the Nrf2/HO‑1 signaling pathway.
研究领域:
药理学
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糖尿病研究
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眼科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
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2025
·Vol. 17
·期 3
·302
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IF 5.5
Jing Zhang,Min Zha,Anping Wan,Satya Siva Kishan Yalamarty,Nina Filipczak,Xiang Li
Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)—on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). Methods The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. Results Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a P app value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. Conclusion The modification of micelle vesicles with different cationic polymers significantly influences their performance in ocular drug delivery. Among the tested formulations, D-M-T stands out due to its multiple advantages, including enhanced transcorneal drug delivery, therapeutic efficacy for DIO, and safety, making it the most promising candidate for ophthalmic applications.
研究领域:
药剂学
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眼科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2019
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IF 2.606
Qi Lan,Donghua Di,Siling Wang,Qinfu Zhao,Yikun Gao,Di Chang,Tongying Jiang
The aim of this study was to develop a novel ocular drug delivery system based on the hydroxypropyl beta cyclodextrin (HP-β-CD) inclusion complex coated with the synthesized chitosan-N-acetyl- l -cysteine conjugate (CS-NAC) for the hydrophobic drug quercetin . The inclusion complex was prepared by the solvent evaporation method, and the concentration of HP-β-CD and CS-NAC was optimized by isolated corneal penetration test. The optimized concentration of HP-β-CD and CS-NAC was 20% (w/v) and 0.1% (w/v), respectively. The CS-NAC/quercetin-HP-β-CD had the effect on improving the ocular penetration with little ocular irritation and could increase the ocular distribution significantly. Meanwhile, Coumarin-6 (C6) labelled CS-NAC/C6-HP-β-CD possessed enhanced fluorescence and located deeper into the epithelium of cornea at the same time point compared with the uncoated one. It could also transport drug through the corneal epithelium by intracellular routes except for intercellular routes. Furthermore, it could delay the occurrence of cataract about 1 d when administrated with full-dosage quercetin. The HP-β-CD inclusion complex coated with CS-NAC is a safe and promising ocular drug delivery system for improving the bioavailability and corneal penetration of hydrophobic drug like quercetin.
研究领域:
药剂学
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眼科学
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产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Jing-Wei Xu,Hao-Nan Li,Deng-Feng Hu,Xiao-Bo Zhang,Wei Wang,Jian Ji,Zhi-Kang Xu,Ke Yao
Phacoemulsification with implantation of intraocular lens (IOLs) has been widely applied as a standard treatment for cataract, which is the leading cause of vision impairment. However, it still remains a critical challenge to prevent posterior capsule opacification (PCO) in terms of postoperative visual quality. Herein, we report IOLs with mussel-inspired coatings for inhibiting lens epithelial cells and then preventing PCO through photothermal conversion effect. The mussel-inspired coatings are deposited on the nonoptical surface areas of IOLs, endowing the modified IOLs with efficient photothermal conversion property. The temperature can be facilely raised to 50–60 °C for the photothermal IOLs (PT-IOLs) by near-infrared (NIR) laser irradiation at a safe intensity of 0.3 W/cm2. These PT-IOLs display high capability of inhibiting lens epithelial cells (LECs) in vitro. Therefore, under routine NIR laser irradiation, New Zealand white rabbits implanted with the PT-IOLs demonstrate significantly lower evaluation of PCO (EPCO) scores than the control groups. The overall results indicate that our PT-IOLs provide a promising choice for the clinical prevention of PCO, thus opening a way to maintain the postoperative visual qualities for cataract patients.
研究领域:
眼科
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生物医学工程
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材料科学
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DOI
PubMed
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