BIOMATERIALS
·
2025
·
IF 12.9
Siting Sheng,Huiling Zhao,Lirui Liu,Dan Chen,Xingdi Wu,Chujun Liu,Xinyu Ma,Jing-Wei Xu,Jian Ji,Haijie Han,Wen Xu
Uveitis, a frequently recurrent inflammatory condition of the uvea, poses a significant risk of visual impairment and blindness, primarily due to the excessive generation of reactive oxygen species (ROS) and the activation of signaling pathways that propagate inflammatory responses. Despite the widespread use of corticosteroid eye drops as a standard treatment, these therapies are hindered by limited efficacy, adverse side effects, and poor ocular bioavailability. To address these challenges, polyethyleneimine (PEI)-modified polydopamine (PDA) carrying microRNA-132-3p (miR-132), namely PEI/PDA@miR-132, was developed to simultaneously neutralize ROS and attenuate inflammation in experimental models of acute and chronic uveitis. Mechanistically, PEI/PDA@miR-132 demonstrated remarkable efficacy by suppressing ROS production, inhibiting the pro-inflammatory polarization of macrophages, and downregulating the I κ B α /nuclear factor-kappa B (NF- κ B) p65 signaling pathway. These effects culminated in the reduction of pro-inflammatory cytokines and mitigation of apoptosis. Therapeutically, PEI/PDA@miR-132 provided significant relief from hallmark symptoms of uveitis, including iris congestion, inflammatory exudation, and retinal folds, while exhibiting superior retinal safety compared to commercially available dexamethasone. Furthermore, it showcased excellent biocompatibility, positioning it as a promising therapeutic strategy for managing oxidative stress- and inflammation-driven diseases such as acute and chronic uveitis.
研究领域:
药理学
·
眼科
·
纳米医学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
2025
·Vol. 66
·期 5
·21-21
·
IF 4.7
Xianyang Liu,Hangjia Zuo,Chao Wu,Na Li,Qian Zhou,Fan Cao,Baorui Chu,Shuhao Zeng,Hui Feng,Yakun Wang,Fengyang Lei,Ke Hu,Shengping Hou
Purpose:Uveitis is an immune-mediated ocular disorder that poses a significant threat to vision, particularly among young and middle-aged adults. The treatment of uveitis is complicated by the presence of the blood-retinal barrier (BRB), which restricts the passage of large molecular drugs into the eye, thus limiting effective therapeutic options. The primary objective of this study is to identify a novel therapeutic agent capable of treating uveitis and explore its underlying mechanism.Methods:In this study, we used a mouse model of experimental autoimmune uveitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) and lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced inflammatory BV2 cells. Evans blue and fundus fluorescein angiography (FFA) experiments were performed to evaluate the destruction of BRB. Silt lamp and hematoxylin and eosin (H&E) staining were conducted to evaluate the inflammatory response. In vivo proteomics and Western blot were carried to investigate the underlying mechanisms.Results:Our study reveals that Muscone significantly alleviates EAU and restores the integrity of BRB. Moreover, Muscone treatment markedly downregulated inflammatory factors within the retinas and BV2 cells. In vivo proteomic combined with liquid chromatography-mass spectrometry (LC-MS) has elucidated that Muscone exerts its anti-inflammatory effects by modulating the PI3K-AKT signaling pathway. Moreover, by using LY294002 to specifically inhibit PI3K, we observed a marked decrease in inflammatory phenotype and BRB destruction of EAU.Conclusions:In summary, this study establishes the protective efficacy of Muscone against the progression of EAU and provides insights into the molecular mechanisms responsible for its therapeutic action.
研究领域:
免疫学
·
眼科学
·
药理学
·
分子生物学
·
神经炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Xue Wang,Lu Liu,Di Wu,Yuxin Hu,Hongzhuo Liu,Yizhou Sun,Guangqi Yan
Noninfectious uveitis (NIU) remains a significant cause of vision impairment, typically managed with glucocorticoids. However, current glucocorticoid implants present considerable side effects, including elevated intraocular pressure and cataracts. To overcome these limitations, we synthesized a novel prodrug, dexamethasone gallate (DG), which possesses the powerful anti-inflammatory ability of dexamethasone (DEX) and exhibits strong antioxidant activity of gallic acid (GA) that helps protect ocular tissues against oxidative stress. DG was formulated into cyclodextrin microparticle suspension eye drops, designed to progressively disintegrate and penetrate ocular tissues effectively. In experimental autoimmune uveitis (EAU) models, DG suspension eye drops demonstrated comparable therapeutic efficacy to conventional DEX eye drops at reduced dosages, significantly reducing anterior and posterior ocular inflammation. Notably, DG formulations substantially minimized intraocular pressure elevation and glucocorticoid-related adverse effects. These findings support the potential of DG suspension eye drops as a safer, efficient, and patient-friendly therapeutic alternative for treating NIU.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Renshu Zhang,Jianhong Zhou,Dan Lin,Yuhan Hu,Bo Jin,Yuqin Wang,Jiaqing Wang,Serhii Vakal,Xingyi Li
Glucocorticoids ( e.g., dexamethasone (Dex)) are the mainstay in the treatment of non-infectious uveitis, but optimal drug delivery system to maximally realize its potent bioactivity is still lacking. In the present study, we rationally designed and screened a dexamethasone-peptide amphiphile (Dex-GGD), which instantly formed a prodrug supramolecular hydrogel in phosphate-buffered saline (PBS, pH = 7.4) without external stimuli for the topical ocular drug delivery. The obtained Dex-GGD hydrogel was thoroughly characterized by rheology, circular dichroism (CD), and transmission electron microscopy (TEM). The results showed that Dex-GGD exhibited a potent in vitro anti-inflammatory capacity in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages with minimal cytotoxicity against L-929 fibroblasts, ARPE-19 cells, and RAW 264.7 macrophages. In a rat model of experimental autoimmune uveitis (EAU), the severity of uveitis was significantly alleviated after the treatment with Dex-GGD hydrogel owing to its potent ability to reduce the influx of inflammatory cells from peripheral blood and suppress the activation of macroglia and microglia in the retina. In contrast to the treatment with an equivalent dose of dexamethasone sodium phosphate (Dexp), the intravitreal injection of Dex-GGD hydrogel hardly induced the apparent ocular side-effects ( e.g. , elevated intraocular pressure or fundus blood vessel tortuosity). As a result, the proposed Dex-GGD prodrug supramolecular hydrogel may be an effective and safe therapeutic option for improving the clinical management of uveitis.
研究领域:
药学
·
眼科
·
免疫学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 40
·期 9
·1101-1109
·
IF 3.815
Li Yu-Tong,Sheng Si-Ting,Yu Bo,Jia Fan,Wang Kai,Han Hai-Jie,Jin Qiao,Wang You-Xiang,Ji Jian
Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species (ROS). Herein, an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate (EC) is designed via phenylboronic esters with improved solubility for the alleviation of uveitis. The antioxidative 4-hydroxybenzyl alcohol (HBA) and EC can be released from the macromolecular EC prodrug under the stimulation of ROS, which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way. The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model. Overall, this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS, but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.
研究领域:
药学
·
眼科学
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Jiaxing Huang,Xiaotang Wang,Na Li,Wei Fan,Xingran Li,Qian Zhou,Jiangyi Liu,Wanqian Li,Zhi Zhang,Xiaoyan Liu,Shuhao Zeng,Hui Yang,Meng Tian,Peizeng Yang,Shengping Hou
Activated microglia in the retina are essential for the development of autoimmune uveitis. Yin-Yang 1 (YY1) is an important transcription factor that participates in multiple inflammatory and immune-mediated diseases. Here, an increased YY1 lactylation in retinal microglia within in the experimental autoimmune uveitis (EAU) group is observed. YY1 lactylation contributed to boosting microglial activation and promoting their proliferation and migration abilities. Inhibition of lactylation suppressed microglial activation and attenuated inflammation in EAU. Mechanistically, cleavage under targets & tagmentation （CUT&Tag） analysis revealed that YY1 lactylation promoted microglial activation by regulating the transcription of a set of inflammatory genes, including STAT3, CCL5, IRF1, IDO1 , and SEMA4D . In addition, p300 is identified as the writer of YY1 lactylation. Inhibition of p300 decreased YY1 lactylation and suppressed microglial inflammation in vivo and in vitro. Collectively, the results showed that YY1 lactylation promoted microglial dysfunction in autoimmune uveitis by upregulating inflammatory cytokine secretion and boosting cell migration and proliferation. Therapeutic effects can be achieved by targeting the lactate/p300/YY1 lactylation/inflammatory genes axis.
研究领域:
免疫学
·
神经科学
·
分子生物学
·
眼科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Shengjin Xiang,Jinrun Chen,Mengyun Deng,Zixiang Wang,Xingyi Li,Dan Lin,Jianhong Zhou
Background Extensive research has revealed the favorable effects of celastrol (CEL) against various diseases, but the role of CEL in autoimmune uveitis remains unexplored. Methods We first assessed the prophylactical and therapeutical effects of CEL on autoimmune uveitis via rat experimental autoimmune uveitis model. After network pharmacology, functional enrichment and molecular docking analyses, we predicted the potential target of CEL and validated its effect on EAU by clinical and histopathological scores, Evans blue staining, immunofluorescence assay and western blotting. Then we evaluated the role of CEL in the gut environment by 16S rRNA sequencing and untargeted metabolomic analysis. Results We confirmed that CEL treatment suppressed the pathological TH17 response, inhibited the migration of inflammatory cells, and preserved the integrity of BRB via targeting STAT3-IL17 pathway. Furthermore, CEL was found to reduce the relative abundance of opportunistic pathogenic bacteria including Clostridium_sensu_stricto_1 , Parasutterella and GCA-900066575 , and enrich the relative abundance of beneficial Oscillospirales and Ruminococcus_torques_group in EAU rats by fecal 16S rRNA sequencing. Meanwhile, CEL treatment reshaped the gut metabolites in the EAU rats by increasing the relative concentrations of cholic acid, progesterone and guggulsterone, and decreasing the relative levels of isoproterenol, creatinine and phenylacetylglutamine. Conclusions CEL exerts its ameliorative effects on the experimental autoimmune uveitis through the dual mechanisms of targeting STAT3 and reprofiling the gut microenvironment.
研究领域:
免疫学
·
药理学
·
微生物学
·
分子生物学
·
眼科学
✓ 已验证
DOI
PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
·
2026
·
IF 13.6
Li Yitao,Zheng Weijia,Ma Jiao,Liu Lu,Yang Xintong,Kuang Junliang,Chan Nickie,Wang Chengqiang,Li Yang,Zhao Aihua,Wang Ruonan,Zheng Xiaojiao,Melino Gerry,Lu Aiping,Yang Xiaolu,Jia Wei
Autoimmune uveitis (AU) lacks targeted therapies beyond immunosuppression. We identified hyodeoxycholate (HDCA), a gut-derived secondary bile acid, as a key immunometabolic regulator in AU. Metabolomics revealed systemic depletion of HDCA and oleic acid (C18:1n9) in AU patients and experimental AU (EAU) mice, correlating with disease severity. HDCA administration effectively attenuated EAU by reducing pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and elevating IL-10. Mechanistically, HDCA inhibits Farnesoid X Receptor in splenic red pulp macrophages, activating SREBP1c-dependent fatty acid synthase, which enhances oleic acid production. Systemic oleic acid suppresses ocular Th17 responses and promotes M2 macrophage polarization, enhancing anti-inflammatory immunity. These findings define a spleen-to-eye immunometabolic axis driven by HDCA-mediated macrophage reprogramming, positioning HDCA as a promising therapeutic for AU.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Guihua Fang,Qiuxiang Wang,Xuewen Yang,Yu Qian,Guowei Zhang,Qiang Zhu,Bo Tang
In this paper, we developed a vesicular phospholipid gels (VPGs) for topical ocular delivery of flurbiprofen (FLB) to treat anterior uveitis. FLB loaded VPGs (FLB VPGs), composed of FLB and egg yolk lecithin , were prepared by high-pressure homogenization technique. The effects of egg yolk lecithin content and homogenization pressure on properties of FLB VPGs, including size, encapsulation efficiency, yield and in vitro release profile were investigated. The resultant FLB VPGs were characterized by the transmission electron microscopy , differential scanning calorimetry , X-ray diffraction, fourier transform infrared spectroscopy , rheological behavior, and storage stability. Corneal permeation experiments revealed that VPGs could improve the transcorneal delivery of FLB under ex vivo conditions. VPGs were nonirritant toward to the rabbit eye, as indicated by slit lamp observation and histological observation. The results of tear pharmacokinetics and in vivo fluorescence imaging showed that VPGs could significantly prolong the precorneal retention time. In vivo biodistribution study indicated that VPGs could significantly improve drug bioavailability in ocular tissues. Moreover, FLB VPGs exhibited excellent anti-inflammatory effect in endotoxin induced uveitis in rabbits. Overall, VPGs are a promising ophthalmic drug delivery system for the treatment of anterior uveitis.
研究领域:
药剂学
·
眼科学
·
药物递送系统
·
炎症
✓ 已验证
产品关联
DOI
高影响因子
Biomedicines
·
2025
·Vol. 13
·期 4
·821
·
IF 3.9
Xinyi Gong,Jingchuan Fan,Hui Huang,Fei Xu,Kaijiao Hu,Jianping Liu,Yi Tan,Feilan Chen
Background/Objectives: Identifying effective and safe treatment options for non-infectious uveitis remains challenging due to chronic and relapsing ocular inflammation. Previous studies have shown that artesunate (ART) plays an immunosuppressive role in several classic autoimmune diseases, including uveitis. However, its impact on the plasma metabolic profile of recurrent autoimmune uveitis remains unclear. This study aims to explore the effect of ART on the plasma metabolic features of recurrent experimental autoimmune uveitis (EAU) in a Lewis rat.Methods: Rats were clinically and pathologically evaluated for the development of recurrent EAU induced by inter-photoreceptor retinoid-binding protein (IRBP) R16 peptide-specific T-cells (tEAU). The disruptive effects of ART on tEAU were investigated to evaluate the potential role of rat recurrent EAU. Differentially expressed metabolites were identified in the plasma of rats by untargeted metabolomics analysis after ART treatment. The differential metabolites were applied to subsequent pathway analysis and biomarker analysis by MetaboAnalyst.Results: ART can significantly alleviate the severity of clinical signs and pathological injuries of eyeballs with tEAU. Both non-supervised principal component analysis and orthogonal partial least-squares discriminant analysis showed 84 differential metabolites enriched in 16 metabolic pathways in the tEAU group compared with heathy controls and 51 differential metabolites enriched in 17 metabolic pathways, including arginine and proline metabolism, alanine metabolism, and aminoacyl-tRNA biosynthesis, in the ART-treated group compared with the tEAU group. Particularly, upregulated L-alanine levels in both alanine metabolism and aminoacyl-tRNA biosynthesis were associated with T-cell activation, while elevated spermidine and N-acetyl putrescine levels in arginine and proline metabolism related to T-cell differentiation proved to be valuable biomarkers for ART treatment.Conclusions: Our study demonstrates that ART treatment can alleviate recurrent uveitis by altering the plasma metabolic characteristics associated with T-cell activation and differentiation, which might provide novel insights for potential therapeutic treatments.
研究领域:
免疫学
·
代谢组学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2025
·
IF 2.5
Jiayu Xie,Ke Li,Lusi Chen,Huiying Zhong,Tao Xiao,Lihua Chen,Haibing He,Hongfei Liu,Guoqing Zhang
Intravitreous long-acting drug delivery system offers an excellent alternative to multiple injections for the treatment of noninfectious uveitis (NIU). However, the adverse effects of non-biodegradable intravitreal implants of fluocinolone acetonide (FA), such as postoperative hypotony and secondary injury during removal of the implant matrix, are frequent occurrence to affect patient’s compliance. Herein, biodegradable poly (lactic-co-glycolic acid) (PLGA)-based microspheres (MS) containing fluocinolone acetonide (FA@MS) were prepared using an optimized electrospray technology with a voltage of 10.07 kV and the receiving distance of 9.87 cm. The obtained FA@MS with the average particle size of 2.25 μm possessed the high encapsulation efficiency (94.85%) and drug content (9.48%). In vitro release demonstrated that FA@MS exhibited sustained release for 30 days, and the release characteristic of FA@MS conformed to the Weibull model. In vivo study in a rabbit NIU model indicated that FA@MS continuously released the drug for at least 28 days in vitreum and progressively decreased inflammation of NIU. Furthermore, the intraocular pressure of rabbits treated with blank MS and FA@MS remained the normal level for 28 days, which demonstrated the favorable biosafety of FA@MS. In conclusion, long-acting release of FA@MS provides a promising formulation for NIU treatment.HIGHLIGHTSA biodegradable FA@MS was prepared using the modified electrospray technology for intravitreal administration.FA@MS exhibited the sustained release characteristics for 30 days in the medium of PBS (pH 7.4) with 0.2% Tween 80.The pharmacodynamics indicated that FA@MS could be continuously released for at least 28 days in vitreum to treat NIU.
研究领域:
药学
·
眼科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Guihua Fang,Qiuxiang Wang,Xuewen Yang,Yu Qian,Guowei Zhang,Bo Tang
Anterior uveitis is a sight-threatening inflammation inside the eyes. Conventional eye drops for anti-inflammatory therapy need to be administered frequently owing to the rapid elimination and corneal barrier. To address these issues, polypseudorotaxane hydrogels were developed by mixing Soluplus micelles (99.4 nm) and cyclodextrins solution. The optimized hydrogels exhibited shear-thinning and sustained release properties. The hydrogels exhibited higher transcorneal permeability coefficient (P app , 1.84 folds) than that of drug solutions. Moreover, animal study indicated that the hydrogels significantly increased the precorneal retention (AUC, 21.2 folds) and intraocular bioavailability of flurbiprofen (AUC Aqueous humor , 17.8 folds) in comparison with drug solutions. Importantly, the hydrogels obviously boosted anti-inflammatory efficacy in rabbit model of endotoxin-induced uveitis at a reduced administration frequency. Additionally, the safety of hydrogels was confirmed by cytotoxicity and ocular irritation studies. In all, the present study demonstrates a friendly non-invasive strategy based on γ- CD-based polypseudorotaxane hydrogels for ocular drug delivery.
研究领域:
药学
·
眼科
·
药物递送系统
·
炎症研究
✓ 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）