INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
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2025
·Vol. 66
·期 3
·44-44
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IF 4.7
Boda Li,Junpeng Liu,Di Zhang,Yiran Chu,Zeying Chen,Jiaruei Tsao,Taige Chen,Jiaxuan Jiang,Kai Hu
Purpose:This study aims to explore the therapeutic efficacy of evodiamine (EVO) in the treatment of dry eye disease (DED).Methods:Mouse models of DED was developed using benzalkonium chloride eye drops and subcutaneous atropine injections. Corneal epithelial defects were assessed by fluorescein sodium staining, and tear secretion was measured with the phenol red thread test. For the in vitro model, human corneal epithelial cells were cultured in a sodium chloride–enriched medium. Phenotypic and mechanistic analyses were conducted using real-time quantitative PCR, Western blotting, flow cytometry, and immunofluorescence staining.Results:The administration of EVO eye drops significantly enhanced tear secretion in mice, ameliorated ocular surface damage, decreased the expression of corneal inflammatory factors, and increased the density of conjunctival goblet cells. Furthermore, EVO reduced oxidative stress by promoting autophagy. Mechanistically, EVO-induced autophagy was mediated via the p53/mammalian target of rapamycin pathway.Conclusions:These findings suggest that EVO is a potential therapeutic agent for the treatment of DED, with its beneficial effects attributed to the activation of autophagy through the p53/mammalian target of rapamycin pathway.
研究领域:
眼科
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
·
IF 5.2
Wanbing Pan,Rong Sun,Yaoyuan Yu,Yuxin Liu,Yinling Mu,Hanyan Gong,Hongxia Fan,Yingchao Zhang,Lutong He,Haibing He,Jingxin Gou,Xing Tang,Tian Yin,Yu Zhang
Effective management of posterior ocular segment disorders necessitates sustained retinal drug delivery and rational therapeutic selection. Despite significant advances, developing drug delivery systems that simultaneously achieve deep tissue penetration and prolonged ocular surface retention remains challenging. To bridge this gap, we engineered a borneol- decorated baicalein nanoemulsion in-situ gel (Bor/Bai-N@GEL) ophthalmic formulation for dry age-related macular degeneration (d-AMD). The system integrates a borneol-decorated baicalein nanoemulsion with an ion- sensitive hydrogel. Comparative analysis revealed Bor/Bai-N@GEL’s superior therapeutic performance, attributable to the prolonged ocular residence time and enhanced transcorneal permeability. Pharmacodynamic profiling demonstrated marked attenuation of inflammatory cytokines, oxidative markers, and apoptotic signaling in murine d-AMD models. In summary, our work provided a meaningful delivery strategy and research basis to treat fundus diseases. This approach offers the potential to conveniently treat early-stage d-AMD at home, improving patient adherence and overall treatment outcomes.
研究领域:
药剂学
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眼科医学
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-25
·
IF 7.4
Ren Jun-Song,Bai Wen,Ding Jing-Juan,Ge Hui-Min,Wang Su-Yu,Chen Xi,Jiang Qin
Background Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization.Methods Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1.Results Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis.Conclusion In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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眼科学
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DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
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2024
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IF 3
Lihong Liang,Xue Yang,Hao Zeng,Kai Liao,Runze Zhang,Bowen Wang,Jin Yuan
This research focused on how upregulation of S100A9 contributed to the pathogenesis of the dry eye disease (DED) and whether S100A9 served as a promising therapeutic target in DED. Public single-cell RNA sequencing (scRNA-seq) data of a lacrimal gland excision (LGE) murine DED model was analyzed. LGE model was established and expression of protein was measured through immunofluorescence and western blot. DED-related signs were evaluated through tear secretion and fluorescent staining. TUNEL was performed to detect the level of cell death. Briefly, S100A9 was recognized as a highly variable gene in the DED group. LGE model was successfully established, and S100A9 showed a time-dependent increase in the corneal epithelia. Autophagic blockage was predicted by the scRNA-seq data in DED, and further verified by decrease of LC3B-II/LC3B-I and increase of SQSTM1 and p-mTOR/mTOR, while S100A9 inhibitor paquinimod (PAQ) reversed the changes. PAQ also downregulated TLR4, and inhibition of TLR4 also alleviated autophagic blockage in DED. Finally, signs of DED, chronic corneal inflammation and cell death got a remission after either inhibition of S100A9 or TLR4. In general, we deduced a S100A9-TLR4-Autophagic blockage pathway in the pathogenesis of DED.
研究领域:
眼科
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免疫学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Science Advances
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2025
·Vol. 11
·期 30
·
IF 12.5
Mei Yang,Xin Chen,Zhongxing Chen,Nan Zhao,Zhenhai Zeng,Xiaomin Huang,Zheng Li,Jiawei Li,Guoli Zhao,Manli Deng,Zhilin Zou,Hongxian Pan,Aodong Chen,Tingting Chen,Yue Wu,Xueyu Fu,Qimanguli Saiding,Na Kong,Wei Tao,Xingtao Zhou,Jinhai Huang
Oxidative stress, an imbalance between the body’s oxidative and antioxidant systems, contributes markedly to the development of numerous ocular surface diseases, particularly dry eye disease (DED). Effective elimination or reduction of reactive oxygen species (ROS) can halt disease progression and alleviate symptoms. This study presents an innovative thermoresponsive, metal-free carbon nanodot (CD) hydrogel, termed F-CD hydrogel, which exhibits potent neutralization capabilities against multiple free radicals, including OH·, O 2 − ·, and ·DPPH. This hydrogel demonstrates remarkable antioxidant, anti-inflammatory, and antiapoptotic capacity, effectively relieving DED symptoms by eliminating ROS at their source. Furthermore, its thermosensitive characteristics enhance the adherence of CDs to the ocular surface. In mouse models of DED, the F-CD hydrogel accelerates epithelial repair, thickens the corneal epithelium, promotes tear secretion, and boosts goblet cell count by up-regulating protective genes while suppressing those promoting apoptosis and oxidative stress. Coupled with its excellent biocompatibility and reduced administration frequency and treatment duration, the F-CD hydrogel emerges as a promising therapeutic approach for DED.
研究领域:
眼科学
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纳米医学
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生物材料
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药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Huimin Wu,Longfei Lin,Xueying Du,Lingling Zhang,Xingbin Yin,Xiaoxv Dong,Xiaofeng Hao,Like Xie,Changhai Qu,Jian Ni
Xiaosheng prescription (XSP) has been used for dry eye disease (DED) for more than 10 years in Eye Hospital of China Academy of Chinese Medicine Sciences. However, the effective ingredients involved have remained unclear, which was investigated in this study by the correlation of ingredient and therapeutic activity. Human corneal epithelial cells (HCEC) cultured with 110 mM NaCl solution in vitro and C57BL/6 mice injected subcutaneously with scopolamine hydrobromide were used to establish dry eye models, and the therapeutic effect of XSP extract 1 was better than that of XSP extract 2 significantly. Then, UPLC-Q-TOF/MS and data analysis program Progenesis QI and Makerlynx XS were used to analyze the potential effective ingredients of XSP, and 4 compounds were speculated and identified, in which Schisandrin and 1 μM of Schisantherin A could obviously increase the cell survival rate of injured cells on the cell model. It can be indicated that Schisandrin and Schisantherin A are probably the potential effective ingredients in XSP for DED.
研究领域:
药理学
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眼科
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中医
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
·
IF 8
Qi Lou,Lu Pan,Shengjin Xiang,Yueting Li,Jiahui Jin,Jingyang Tan,Baoshan Huang,Kaihui Nan,Sen Lin
Introduction Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.
研究领域:
眼科
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药学
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细胞生物学
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炎症
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产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 45
·2102485
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IF 13.281
Tianyou Wang,Qianqian Fan,Jiaxu Hong,Zhan Chen,Xujiao Zhou,Jianhua Zhang,Yiqin Dai,Hao Jiang,Zhipeng Gu,Yiyun Cheng,Yiwen Li
The therapeutic potential of nanomaterials toward oxidative damage relevant diseases has attracted great attentions by offering promising advantages compared with conventional antioxidants. Although different kinds of nanoantioxidants have been well developed, the facile fabrication of robust and efficient nanoscavengers is still met with challenges like the use of toxic and high-cost subunits, the involvement of multistep synthetic process, and redundant purification work. Herein, a direct fabrication strategy toward polyphenol nanoparticles with tunable size, excellent biocompatibility, and reactive oxygen species (ROS) scavenging capacities from grape seed via an enzymatic polymerization method is reported. The resulting nanoparticles can efficiently prevent cell damage from ROS and exert promising in vivo antioxidant therapeutic effects on several oxidative stress-related diseases, including accelerating wound healing, inhibiting ulcerative colitis, and regulating the oxidative stress in dry eye disease. This study can stimulate the development of more kinds of low-cost, safe, and efficient biomass-based antioxidative nanomaterials via similar fabrication methodologies.
研究领域:
纳米技术
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药学
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
Endocrine Metabolic & Immune Disorders-Drug Targets
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2025
·Vol. 26
·期 1
·E18715303382831
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IF 2
Yuting Chen,Jie Min,Xiali Yu,Haixiang Ni,Yamei Jin
IntroductionAn increase in the intraorbital adipose tissue is the main pathological feature of thyroid-associated ophthalmopathy (TAO). IGF-1R activates PI3K/AKT signaling and accelerates adipogenesis. Pingmu decoction has been demonstrated to promote orbital adipocyte apoptosis; however, less is reported regarding the action mechanism of Danshenol A (DA), a single active ingredient of Salvia miltiorrhiza (Danshen). Accordingly, this study aimed to investigate the role and association of DA and IGF-1R in the proliferation and lipid accumulation of orbital adipocytes.MethodsPrimary human orbital preadipocytes were chosen and authenticated using immunofluorescence. Cells were treated with the IGF-1R agonist ginsenoside Rg5, IGF-1R overexpression plasmid, dexamethasone (Dex), and/or DA, after which cell proliferation and differentiation were assessed by cell counting kit-8 (CCK-8), oil red O staining, real-time quantitative polymerase chain reaction, and Western blot assays.ResultsOrbital preadipocytes showed positive expression of Pref-1. Treatment with IGF-1R agonist, as well as Dex, promoted orbital adipocyte viability and lipid accumulation, and increased the expression of adiponectin and leptin. It was observed that the overexpression of IGF-1R boosted PI3K/AKT activation and elevated PPARγ and C/EBPα expressions. Importantly, DA reversed the effects of IGF-1R on cell viability, lipid accumulation, and the PI3K/AKT signaling pathway.DiscussionThis study, for the first time, revealed the molecular mechanism by which DA regulates orbital fat metabolism through targeted inhibition of the IGF-1R/PI3K/AKT signaling axis. Notably, IGF-1R overexpression partially counteracted the inhibitory effect of DA, suggesting that this component has multi-target regulatory characteristics.ConclusionThis study not only reveals a new mechanism by which DA treats TAO but also provides theoretical support for the treatment of adipose metabolism.
研究领域:
内分泌学
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眼科学
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分子生物学
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信号转导
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脂肪代谢
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中药药理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2023
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IF 19
Zhongxing Chen,Zheng Li,Nana Tang,Yida Huang,Siheng Li,Wenjin Xu,Qing Wang,Xin Chen,Nan Zhao,Zhenhai Zeng,Yichen Xiao,Xinyi Chen,Jiawei Li,Xingtao Zhou,Guisheng Li,Mei Yang,Jinhai Huang
Dry eye disease (DED) is a widespread ophthalmic illness that inflicts massive economic and medical burdens on society. Although oxidative stress is closely associated with the onset of DED, barely any quantities of antioxidants are clinically available owing to low efficiency, toxicity, and poor bioavailability. Cerium-based nanozymes possess promising enzyme-mimetic activities in scavenging reactive oxygen species (ROS). Moreover, the ultra-small metal–organic frameworks (MOFs) have the potential for more efficient drug delivery, ROS elimination, and therapeutic efficacy. However, the development of ultra-small cerium-based MOFs (Ce-MOFs) is limited to a small minority due to challenges in the synthetic process and stability. By simply adjusting raw ingredients concentrations, three types of Ce-MOFs with distinct particle sizes are synthesized: Ce-MOF 1 (213 nm), Ce-MOF 2 (36 nm), and Ce-MOF 3 (2 nm). In comparison, the obtained ultra-small Ce-MOF 3 exhibited superior ROS scavenging and antioxidant capacity, decreased cytotoxicity, and excellent ocular penetration. Therapeutically, Ce-MOF 3 is demonstrated to be highly efficient in alleviating DED by suppressing oxidative stress and inflammation, boosting corneal epithelial repair, and facilitating tear secretion recovery. The novel ultra-small Ce-MOF 3 may serve as a promising alternative treatment for DED and other ROS-related disorders when combined with ocular biocompatibility.
研究领域:
纳米技术
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材料科学
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生物医学工程
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药学
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眼科
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-11
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IF 9.429
Xie Maowen,Yao Guang,Zhang Tianyao,Wang Qian,Mo Xiaoyi,Dong Qiwei,Lou Wenhao,Lu Fang,Pan Taisong,Gao Min,Jiang Dawei,Zhao Kangning,Lin Yuan
As a non-invasive innovative diagnosis platform, advanced flexible contact lenses can dynamically monitor vital ocular indicators, spot abnormalities and provide biofeedback guidance for real-time diagnosis and rehabilitation tracking of chronic eye diseases. However, most of the state-of-the-art reported contact lenses either can only monitor a single indicator at a time or realize multifunctional integration based on multiple materials. Herein, we developed a flexible multifunctional contact lens based on inorganic γ-Fe 2 O 3 @NiO magnetic oxide nanosheets, which can be attached conformally and seamlessly to the eyeball to simultaneously monitor glucose level in tears, eyeball movement, and intraocular pressure. The optimized contact lens has a reliable glucose detection limit (0.43 μmol), superior eye movement measurement accuracy (95.27%) and high intraocular pressure sensitivity (0.17 MHz mmHg − 1 ). This work presents a concept in the biochemical and biophysical integrated sensing of ocular signals using contact lens via an innovative material, and provides a personalized and efficient way for health management. Graphical Abstract
研究领域:
生物医学工程
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纳米技术
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视光学
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材料科学
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健康监测
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Qi Liang,Rongjie Guo,Jia-Ruei Tsao,Yun He,Chenchen Wang,Jiaxuan Jiang,Di Zhang,Taige Chen,Tingting Yue,Kai Hu
Dry eye disease (DED) is a multifactorial disease, and oxidative stress plays a crucial role in its pathogenesis. Recently, multiple studies have shown that upregulation of autophagy can protect the cornea from oxidative stress damage. The present study investigated the therapeutic effects of salidroside, the main component of Rhodiola crenulata , in both in vivo and in vitro dry eye models. The results showed that topical eye drop treatment with salidroside restored corneal epithelium damage, increased tear secretion, and reduced cornea inflammation in the DED mice. Salidroside activated autophagy through AMP-activated protein kinase (AMPK)-sirtuin-1 (Sirt1) signaling pathway, which promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and increased the expression of downstream antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). This process restored antioxidant enzyme activity, reduced reactive oxygen species (ROS) accumulation, and alleviated oxidative stress. The application of autophagy inhibitor chloroquine and AMPK inhibitor Compound C reversed the therapeutic efficacy of salidroside, validating the above findings. In conclusion, our data suggest that salidroside is a promising candidate for DED treatment.
研究领域:
药理学
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眼科
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）