Frontiers in Nutrition
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2022
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IF 6.59
Jiang Hong,Fan Yahui,Li Juan,Wang Jiaqi,Kong Liyun,Wang Lina,Li Zhaofang,Ma Mei,Shi Xin,Liu Sijiao,Shi Jia,Zhu Hailu,Liu XiaoHong,Ma Le
Background and Purpose: Data from studies support a beneficial effect of carotenoids and vitamins on an age-related macular degeneration (AMD) risk. However, studies on the relations between blood levels of these nutrients and AMD are limited and provided conflicting results. The objective of this case-control study and meta-analysis was to examine whether the blood concentrations of carotenoids and vitamins were associated with the risk of AMD.Methods: A total of 164 cases of AMD and an equal number of controls are individually matched according to age and gender among the participants, who provided blood samples in the Xi'an Eye Study. Plasma carotenoids and vitamins were measured using reversed-phase high-performance liquid chromatography. Bonferroni-corrected covariate-adjusted conditional logistic regression were used to estimate AMD risk by category of these nutrients in the multivariable-adjusted model. Nine studies were identified for the meta-analysis and calculated pooled risk estimates by means of a random-effects model.Results: Plasma concentrations of examined carotenoids and vitamins were significantly lower in patients with AMD than those in controls. Plasma concentrations of examined carotenoids and vitamins were significantly lower in patients with AMD than those in controls. After a multivariate adjustment for body mass index, blood cholesterol, and other lifestyle risk factors, higher lutein/zeaxanthin content in plasma was significantly associated with a decreased risk of AMD, and the odds ratio (OR) comparing the top and bottom tertiles was 0.21 (95% CI: 0.05, 0.84; Ptrend = 0.024). Associations for β-carotenes (OR: 0.11; 95% CI: 0.02, 0.50; Ptrend < 0.001), and β-cryptoxanthin (OR: 0.08, 95% CI: 0.02, 0.39; Ptrend < 0.001) were similar to that for lutein/zeaxanthin. Inverse associations were also observed for a higher level of retinol (OR: 0.14, 95% CI: 0.03, 0.61; Ptrend = 0.006) and α-tocopherol (OR: 0.25, 95% CI: 0.06, 0.98; Ptrend = 0.006). In the meta-analysis, a protective effect was detected for AMD among the participants with high blood lutein/zeaxanthin level (OR: 0.53, 95% CI: 0.40, 0.72, P < 0.001), compared to those with low level. Similar inverse associations were seen for β-carotene (OR: 0.48, 95% CI: 0.28, 0.84, P = 0.010), β-cryptoxanthin (OR: 0.48, 95% CI: 0.23, 1, P = 0.049), lycopene (OR: 0.70, 95% CI: 0.54, 0.90, P = 0.006) and α-tocopherol (OR: 0.50, 95% CI: 0.31, 0.81, P = 0.005).Conclusions: Results of the case-control study were consistent with findings from the meta-analysis, indicating that higher concentrations of carotenoids and vitamins were inversely associated with the AMD risk. Our finding supports the current notion that these nutrients are likely to affect the development of AMD and may help to refine the strategies for the prevention of age-related eye diseases.
研究领域:
眼科学
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营养流行病学
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公共卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
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2016
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IF 2.998
Xinyi Ren,Jia Li,Xianxing Xu,Chunming Wang,Yuanguo Cheng
Uncontrolled activation of complement and upregulation of vascular endothelial growth factor (VEGF) play fundamental roles in age-related macular degeneration (AMD). However, most drugs used to treat AMD focus on a single target, and the percentage of effectively treated patients in clinical practice needs to be improved. Therefore, novel AMD treatment approaches are needed. IBI302 is a novel bispecific decoy receptor fusion protein designed with both a VEGF inhibition domain and a complement cascade inhibition domain, which are connected by the Fc region of human immunoglobulin . In this study, we systematically evaluated the binding affinity between IBI302 and VEGF isoforms and complement proteins by using surface plasmon resonance (SPR) technology. Anti-VEGF blockers (aflibercept and bevacizumab) and complement receptor 1 were used as references. The SPR assay results indicated that IBI302 could bind different VEGF isoforms and complement proteins with high affinity. The biological activity of IBI302 was also studied. IBI302 showed an inhibitory effect on human primary umbilical vein endothelial cell proliferation and the activation of complement pathways in vitro. Finally, the pharmacokinetic (PK) properties of IBI302 were evaluated in rhesus monkeys . The PK results showed that after a 0.5 mg/eye intravitreal dosage, IBI302 became rapidly distributed from the vitreous humor into targeted tissues and remained active over 504 h. Overall, the favorable anti-angiogenic and anti-complement effects of IBI302 along with the good PK profiles in rhesus monkeys support the selection and development of IBI302 as a promising candidate for AMD treatment.
研究领域:
眼科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2021
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IF 8.947
Guoxin Tan,Dandan Liu,Renfang Zhu,Hao Pan,Jiayang Li,Weisan Pan
Retinal diseases, including age-related macular degeneration (AMD), are a major cause of blindness. Efficient delivery of therapeutic genes to retinal cells to treat retinal disease is a formidable challenge. In this study, we developed a core-shell nanoplatform composed of a core and two external layers for targeted delivery of the gene to the retina. The inner core was composed of amino acid-functionalized dendrimers and a nuclear localization signal (NLS) for DNA complexation, nuclear transport and efficient transfection. The inner core was coated in a lipid bilayer that comprised pH-sensitive lipids as the inner shell layer. Hyaluronic acid (HA)-1,2-dioleoylphosphatidylethanolamine (DOPE) as the outermost shell layer was used for retinal cell targeting. This core-shell nanoplatform was developed so that the mobility in the vitreous body of these negatively charged carriers would not be affected by their surface charge, allowing diffusion into the retina, uptake into the retinal cells via CD44-mediated internalization , and finally transport into the nucleus by the NLS. The designed nanoparticles showed safety both in vitro and in vivo and inhibited the expression of VEGF under hypoxia-mimicking conditions. In vitro angiogenesis assays exhibited significant inhibitory effects on cell migration and tube formation. The in vivo assays indicated that this nanoplatform could be delivered to the retina. Taken together, this nanoplatform has the potential to transfer gene material into the retina for the treatment of retinal diseases, including AMD. Statement of significance It remains a challenge to develop an efficient nonviral vector for gene therapy, especially retinal gene therapy. Various barriers exist in gene delivery and the unique ocular environment, making gene delivery to the retina difficult. In this study, we designed a negatively charged core-shell nanoplatform (HD-NP PND ) for the targeted delivery of gene to the retina. The developed nanoplatform possessed excellent transfection efficiency and safety both in vitro and in vivo. It efficiently delivered a gene to the retina. The results of this study suggested that this core-shell nanoplatform has the potential to deliver genes to the retina to treat retinal diseases, including age-related macular degeneration (AMD).
研究领域:
基因治疗
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纳米技术
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眼科学
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分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2024
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IF 7.1
Chaojuan Wen,Xinyue Yu,Jingya Zhu,Jingshu Zeng,Xielan Kuang,Youao Zhang,Shiyu Tang,Qingjiong Zhang,Jianhua Yan,Huangxuan Shen
Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly, is primarily characterized by the degeneration of the retinal pigment epithelium (RPE). However, effective therapeutic options for dry AMD are currently lacking, necessitating further exploration into preventive and pharmaceutical interventions. This study aimed to investigate the protective effects of gastrodin on RPE cells exposed to oxidative stress. We constructed an in vitro oxidative stress model of 4-hydroxynonenal (4-HNE) and performed RNA-seq, and demonstrated the protective effect of gastrodin through mouse experiments. Our findings reveal that gastrodin can inhibit 4-HNE-induced oxidative stress, effectively improving the mitochondrial and lysosomal dysfunction of RPE cells. We further elucidated that gastrodin promotes autophagy and phagocytosis through activating the PPARα-TFEB/CD36 signaling pathway. Interestingly, these outcomes were corroborated in a mouse model, in which gastrodin maintained retinal integrity and reduced RPE disorganization and degeneration under oxidative stress. The accumulation of LC3B and SQSTM1 in mouse RPE-choroid was also reduced. Moreover, activating PPARα and downstream pathways to restore autophagy and phagocytosis, thereby countering RPE injury from oxidative stress. In conclusion, this study demonstrated that gastrodin maintains the normal function of RPE cells by reducing oxidative stress, enhancing their phagocytic function, and restoring the level of autophagic flow. These findings suggest that gastrodin is a novel formulation with potential applications in the development of AMD disease.
研究领域:
眼科学
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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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神经科学
✓ 已验证
DOI
PubMed
高影响因子
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