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Lycium barbarum polysaccharides related RAGE and Aβ levels in the retina of mice with acute ocular hypertension and promote maintenance of blood retinal barrier

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Neural Regeneration Research 2020年第12期15卷 2344-2352页

作者： Xue-Song Mi Qian Feng Amy Cheuk Yin Lo raymond chuen-chung chang Sookja Kim chung Kwok-Fai So Department of Ophthalmology the First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Guangdong-Hong Kong-Macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina changsha Academician Expert Workstation Aier Eye Hospital GroupChangshaHunan ProvinceChina State Key Laboratory of Brain and Cognitive Sciences Hong Kong Special Administrative RegionChina Department of Ophthalmology The University of Hong KongHong Kong Special Administrative RegionChina Faculty of Medicine Macao University of Science and TechnologyMacao Special Administrative RegionChina School of Biomedical Science LKS Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina

Our previous study verified the protective effects of Lycium barbarum polysaccharides(LBP)on retinal neurons and blood vessels in acute ocular hypertension(AOH)*** investigate the effect of LBP on the reactivity of retinal glial cells,an AOH mouse model was established in one eye by maintaining ocular hypertension of 90 mm Hg for 60 *** LBP solution(1 mg/kg)or phosphate-buffered saline was administrated to the mice by gavage daily,starting 7 days before the AOH insult and continuing until the mice were sacrificed for specimen collection on day 4 *** AOH insult,increased numbers of astrocytes and microglia were observed,together with decreased expression of the following glial cell biomarkers in the retinal ganglion cells of AOH mice:glial fibrillary acidic protein,glutamine synthetase,aquaporin-4,S-100 proteins,ionized calcium-binding adaptor molecule 1,amyloid precursor protein and receptor of advanced glycosylation *** intervention with LBP,the above changes were significantly ***,morphological remodeling of blood vessel-associated retinal astrocytes,marked by glial fibrillary acidic protein,was also *** results,taken together,suggest that LBP regulated the production of amyloid-βand expression of receptor of advanced glycosylation end-products,as well as mediating the activity of retinal glial cells,which may lead to the promotion of better maintenance of the blood-retinal barrier and improved neuronal survival in AOH *** study was approved by the Committee for the Use of Live Animals in Teaching and Research(approval ***-#1664-08).

关键词： astrocyte blood-retinal barrier glial cell Lycium barbarum microglia model plasticity remodel retina

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Modulation of Neuroimmune Responses on Glia in the Central Nervous System： Implication in Therapeutic Intervention against Neuroinflammation

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Cellular & Molecular Immunology 2009年第5期6卷 317-326页

作者： raymond chuen-chung chang Kin Chiu Yuen-Shan Ho Kwok-Fai So Laboratory of Neurodegenerative Diseases Depamnent of Anatomy LKSFaculty of Medicine University of Hong Kong Pokfulam Hong KongSAR China Research Centre of Heart Brain Hormone and Healthy Aging LKSFaculty of Medicine University of Hong Kong Pokfulam Hong KongSAR China State Key Laboratory for Brain and Cognitive Sciences University of HongKong. Pokfulam Hong Kong SAR China Department of Anatomy LKS Faculty of Miedicine The University of Hong Kong Rm.

It has long been known that the brain is an immunologically privileged site in normal conditions. Although the cascade of immune responses can occur as long as there is a neuronal injury or a potent immune stimulation, how the brain keeps glial cells in a quiescent state is still unclear. Increasing efforts have been made by several laboratories to elucidate how repression oi~ immune responses is achieved in the neuronal environment. The suppression factors include neurotransmitters, neurohormones, neurotrophic factors, anti-inflammatory factors, and cell-cell contact via adhesion molecules or CD200 receptor. This review discusses how these factors affect the cascade of cerebral immune responses because no single factor listed above can fully account for the immune suppression. While several factors contribute to the suppression of immune responses, activation of glial cells and their production of pro-inflammatory factors do occur as long as there is a neuronal injury, suggesting that some neuronal components facilitate immune responses. This review also discusses which signals initiate or augment cerebral immune responses so that stimulatory signals override the suppressive signals. Increasing lines of evidence have demonstrated that immune responses in the brain are not always detrimental to neurons. Attempt to simply clear off inflammatory factors in the CNS may not be appropriate for neurons in neurological disorders. Appropriate control of immune cells in the CNS may be beneficial to neurons or even neuroregeneration. Therefore, understanding the mechanisms underlying immune suppression may help us to reshape pharmacological interventions against inflammation in many neurological disorders.

关键词： neural cell adhesion molecule neurotrophins potassium ions microglia neuroinflammation

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Modulation of morphological changes of microglia and neuroprotection by monocyte chemoattractant protein-1 in experimental glaucoma

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Cellular & Molecular Immunology 2010年第1期7卷 61-68页

作者： Kin Chiu Sze-Chun Yeung Kwok-Fai So raymond chuen-chung chang Laboratory of Neurodegenerative Diseases Department of AnatomyUniversity of Hong KongPokfulamHong KongChina State Key Laboratory of Brain and Cognitive Sciences University of HongKongPokfulamHongKongChina Research Centre of Heart BrainHormone and Healthy AgingLiKa Shing Faculty of MedicineUniversity of Hong KongPokfulamHong KongChina

Monocyte chemoattractant protein-1(MCP-1)/CCL2 is a C–C chemokine involved in the activation and recruitment of monocytic cells to injury ***-1/CCL2 can induce either neuroprotection or neurodestruction in vitro,depending on the experimental *** aim to use MCP-1/CCL2 as an experimental tool to investigate the morphological changes of microglia when loss of healthy retinal ganglion cells(RGCs)is exacerbated or attenuated in an experimental glaucoma *** a high concentration(1000 ng)of MCP-1/CCL2 and lipopolysaccharide(LPS)-exacerbated RGC loss,100 ng MCP-1/CCL2 provided neuroprotection towards *** MCP-1/CCL2(100 ng)also upregulated insulin-like growth factor-1(IGF-1)immunoreactivity in the *** neuroprotective effect of MCP-1/CCL2 was not due to the massiveinfiltration of microglia/*** together,this is the first report showing that an appropriate amount of MCP-1/CCL2 can protect RGCs in experimental glaucoma.

关键词： glaucoma IGF-1 MCP-1/CCL2 microglia neuroprotection

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Effect of Lycium barbarum Polysaccharides on the expression of endothelin-1 and its receptors in an ocular hypertension model of rat glaucoma

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Neural Regeneration Research 2012年第9期7卷 645-651页

作者： Xue-Song Mi Kin Chiu Geoffrey Van Justin Wai chung Leung Amy Cheuk Yin Lo SookjaKim chung raymond chuen-chung chang Kwok-Fai So Department of Anatomy and the State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina Eye Institute Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina Research Centre of Heart BrainHormone and Healthy AgingLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina The Joint Laboratory for Brain Function and Health （BFAH） Jinan University and The University of Hong Kong Guangzhou 510632Guangdong Province China

Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells （RGCs） in a rat chronic ocular hypertension （COH） model. Here, we investigated the expression of endothelin-1 （ET-1）, a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure （IOP） was induced in the right eye of SD rats using argon laser photocoagulation. （1） The expression of ET-1, ETA and ETB in normal and COH retinas was studied. （2） Some COH rats were fed daily with Lycium barbarum Polysaccharides （LBP） using 1 mg/kg or phosphate-buffered saline （PBS） for 3 weeks （started 1 week before photocoagulation）. The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that （1） Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. （2） After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. （3） By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.

关键词： retinal ganglion cell Lycium barbarum Polysaccharides glaucoma endothelin-1

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Research advances on the usage of traditional Chinese medicine for neuroprotection in glaucoma

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Journal of Integrative Medicine 2013年第4期11卷 233-240页

作者： Xue-song Mi Jing-xiang Zhong raymond chuen-chung chang Kwok-Fai So Department of Ophthalmology the First Affiliated Hospital Department of Anatomy and the State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of Medicine The University of Hong Kong Guangdong-Hong Kong-Macao Institute of Central Neural System Regeneration Jinan University

Progressive loss of retinal ganglion cells （RGCs） and their axons is the main pathogenesis of glaucoma. The cause of glaucoma is not fully understood, but the neurodegeneration of glaucoma involves many mechanisms such as oxidative stress, glutamate toxicity and ischemia/ reperfusion insult. In order to target these mechanisms, multiple neuroprotective interventions have been investigated to prevent the death of RGCs. Of note are some tonic herbs from the traditional Chinese medicine （TCM） pharmacopeia that have shown neuroprotective effects in glaucoma. TCM differs from Western medicine in that TCM exhibits complicated bioactive com- ponents, triggering many signaling pathways and extensive actions on vital organs. Modern scientific approaches have demonstrated some of their underlying mechanisms. In this review, we used Lycium barbarum and Ginkgo biloba as examples to elaborate the characteristics of TCM and their potential applications in neuroprotection in glaucoma.

关键词： neuroprotection neuroprotective agents traditional Chinese medicine glaucoma review

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Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

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Neural Regeneration Research 2015年第12期10卷 1976-1981页

作者： Hua Wang Benson Wui-Man Lau Ning-li Wang Si-ying Wang Qing-jun Lu raymond chuen-chung chang Kwok-fai So Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical University Beijing Ophthalmology & Visual Sciences Key Laboratory Department of Rehabilitation Science The Hong Kong Polytechnic University Department of Anatomy Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulam The State Key Laboratory of Brain and Cognitive Sciences The University of Hong Kong Research Centre of Heart BrainHormone and Healthy AgingFaculty of MedicineThe University of Hong Kong Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulam GMH Institute of Central Nervous System Regeneration Jinan University

Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic ***,it remains unclear regarding the effects of Lycium barbarum polysaccharides,the main component of Lycium barbarum,on in vivo proliferation of adult ciliary body *** this study,adult rats were intragastrically administered low-and high-dose Lycium barbarum polysaccharides（1 and 10 mg/kg）for 35 days and those intragastrically administered phosphate buffered saline served as *** number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups,in particular low-dose Lycium barbarum polysaccharides group,was significantly greater than that in the phosphate buffered saline ***-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic *** findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype.

关键词： nerve regeneration traditional Chinese medicine Lycium barbarum polysaccharides Lycium barbarum (wolJberry) retinal disease neurogenesis adult neural regeneration

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Neuronal damage and blood-retinal barrier disruption in retinal ischemia/reperfusion injury:protective effects of Lycium barbarum polysaccharides

Neuronal damage and blood-retinal barrier disruption in reti...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Amy Cheuk Yin Lo Suk-Yee Li chung-Man Yeung raymond chuen-chung chang Kwok-Fai So David Wong Eye Institute Li Ka Shing Faculty of MedicineThe University of Hong Kong Research Center of Heart BrainHormone and Healthy AgingLi Ka Shing Faculty of MedicineThe University of Hong Kong Department of Anatomy Li Ka Shing Faculty of MedicineThe University of Hong Kong

＜正＞Objective Neuronal cell death,glial cell activation,retinal swelling and oxidative injury are complications in retinal ischemia/reperfusion（I/R） *** barbarum polysaccharides（LBP）,extracts from the wolfberries, are good for "eye health" in Chinese *** aim of our present study is to explore the use of LBP in retinal I/R *** Retinal I/R injury was induced by surgical occlusion of the internal carotid *** to induction of ischemia,mice were fed orally with either vehicle（PBS） or LBP（1 mg/kg） once a day for 1 week. Ischemia was maintained for 2 hours and reperfusion was then allowed for 22 ***-embedded retinal sections were *** cells were counted while apoptosis was assessed using TUNEL *** levels of glial fibrillary acidic protein（GFAP）,aquaporin-4（AQP4）,poly（ADP-ribose）（PAR） and nitrotyrosine （NT） were investigated by *** integrity of blood-retinal barrier（BRB） was examined by IgG extravasation *** Decreased viable cell count and apoptosis were found in the ganglion cell layer （GCL） and the inner nuclear layer（INL） of the vehicle-treated I/R ***,increased retinal thickness, GFAP activation,AQP4 up-regulation,IgG extravasation and PAR expression level were observed in the vehicletreated I/R *** importantly,many of these changes were diminished or abolished in the LBP-treated I/R *** Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death,apoptosis, glial cell activation,aquaporin water channel up-regulation,disruption of BRB and oxidative *** present study suggests that LBP may have a neuroprotective role in ocular diseases in which I/R is a feature.

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Neuroprotective effects of Lycium barbarum polysaccharides on acute ischemic stroke injury

Neuroprotective effects of Lycium barbarum polysaccharides o...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Amy Cheuk-Yin LO chung-Man YEUNG Suk-Yee LI raymond chuen-chung chang Kwok-Fai SO David WONG Eye Institute Li Ka Shing Faculty of MedicineThe University of Hong Kong Research Center of Heart BrainHormone and Healthy AgingLi Ka Shing Faculty of MedicineThe University of Hong Kong Department of Anatomy Li Ka Shing Faculty of MedicineThe University of Hong Kong St Paul’s Eye Unit University of LiverpoolUK

＜正＞Objective The polysaccharides in Lycium barbarum,a well known traditional Chinese medicine,have been demonstrated to display multiple biological effects such as anti-aging,anti-tumor and *** the present study,we aimed to evaluate the effects of Lycium barbarum polysaccharides（LBP） on murine brain injury after induction of acute ischemic stroke by middle cerebral artery occlusion（MCAO）.Methods Mice were orally treated with either vehicle（PBS） or LBP（1 mg/kg or 10 mg/kg） for 1 week before induction of cerebral ischemia by *** 2 h of ischemia followed by 22 h of reperfusion,animals were evaluated for neurological *** after scoring of the neurological deficits,brains were isolated,cut into 6 coronal slices of 2 mm thickness and stained with 2%2,3,5-triphenyltetrazolium chloride（TTC） to detect lesion *** posterior surface of each brain slice was subsequently photographed and analyzed using a digital image analysis *** area,volume,and hemispheric brain swelling were calculated using an indirect method in which the effects of edema and brain swelling have been ***（1） Mice treated with either 1 mg/kg LBP or 10 mg/kg LBP（n=7 for each group） had less neurological deficits than the vehicle-treated mice（n=8）（vehicle=2.0+/-0.3,1 mg/kg LBP=1.4+/-0.2,10 mg/kg LBP=1.1+/-0.1）.（2） TTC staining revealed a significantly smaller infarct area in brain slice number 4 in the LBP-treated mice when compared with the vehicle-treated mice（vehicle=35.4+/- 4.2%,1 mg/kg LBP=17.5+/-5.8%,10 mg/kg LBP=17.6+/-4.9%）.（3） Consistent with the infarct area data,the overall infarct volumes were decreased in the LBP-treated groups（vehicle=25.8+/-3.1%,1 mg/kg LBP=215+/-2.5%,10mg/kg LBP=16.6+/-2.7%）. （4） Mice treated with LBP displayed less hemispheric brain swelling（vehicle=11.1+/-0.9%,1 mg/kg LBP=9.7+/-1.1%,10mg/kg LBP=7.9+/-0.6%）.Conclusions Taken together,these data indicate that treatment with LBP for 1 week could protect the mouse

关键词： neuroprotection animal model oxidative stress

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Neuroprotective Effects of Lyicium Barbarum（Wolfberry） on Retinas after Partial Optic Nerve Transection

Neuroprotective Effects of Lyicium Barbarum（Wolfberry） on ...

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第十四届全国中药和天然药物学术研讨会

作者： Hongying Li Patrick HW Chu Henry HL Chan Yuxiang Liang Kin Chiu raymond chuen-chung chang Kwok-Fai So The University of Hong Kong

＜正＞Our group has shown that the polysaccharides extracted from Lycium barbarum（LBP）are neuroprotective for retinal ganglion cells（RGCs）in different animal *** RGCs from secondary degeneration is a promising direction for therapy in glaucoma *** partial optic nerve transection（PONT）model can be used to study secondary degeneration of RGCs because primary and secondary degeneration of RGCs can be

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*** rescue in retinitis pigmentosa by the treatment of Lycium barbarum(Random Clinical Trial)

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Annals of Eye Science 2017年第1期 356-356页

作者： Henry Chan Hang-I Lam Kwok-Fai So raymond chuen-chung chang Shiu-Ming Lai Chi-Wai Do Iris F.F.Benzie Chin-Pan Leung Kai-Yip Choi Man-Pan Chin Zhe-Chuang Li Wing-Yan Yu Laboratory of Experimental Optometry(Neuroscience) School of OptometryThe Hong Kong Polytechnic UniversityHong Kong SARChina Guangdong-Hongkong-Macao(GHM)Institute of CNS Regeneration Jinan UniversityGuangzhouChina School of Biomedical Sciences The University of Hong KongHong Kong SARChina Department of Ophthalmology The University of Hong KongHong Kong SARChina Laboratory of Experimental Optometry(Biophysic) School of OptometryThe Hong Kong Polytechnic UniversityHong Kong SARChina Department of Health Technology and Informatics The Hong Kong Polytechnic UniversityHong Kong SARChina Private practice Chinese medical doctor

Retinitis pigmentosa(RP)is a group of heredofamilial retinal diseases which is characterized by night blindness and progressive visual field *** study aims to study the treatment effect of Lycium barbarum(LB)on retinal functions and structure of RP *** study is a double-masked randomized controlled *** subjects received scheduled eye examination including visual acuity(VA),Humphrey field analysis(HFA),ganzfeld flash electroretinogram(ffERG)and optical coherence tomography(OCT).The suitable subjects were randomly allocated to either LB-treatment or placebo groups with the supply of LB or placebo for 12 *** were total 41 RP subjects(22 in LB group and 19 in placebo group)completed the 12 months *** compliance rates for LB and placebo groups were 89.8%±12.5%and 85.3%±7.7%*** compared with placebo group,there were no deteriorations of both high and low contrast VA in LB group(Pchanges found in the sensitivity of central visual field between two *** results confirm that the 12-month LB treatment for RP patients had neuroprotective effect on retina and is believed to delay or minimize the deterioration of visual function in RP.

关键词： Retinitis pigmentosa(RP) Lycium barbarum(LB) neuroprotection cone retina

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