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Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 268-276页

作者： ZHENG Xueying GUO Liang LAI Siyi LI Fengyue LIANG Mingli LIU Wanting MENG Chun LIU Guanghui Department of Bioengineering College of Biological Science and BiotechnologyFuzhou UniversityFuzhou 350104China Eye Institute of Integrated Chinese and Western Medicine Fujian University of Traditional Chinese MedicineFuzhou 350004China Department of Ophthalmology Affiliated People's Hospital(Fujian Provincial People's Hospital)Fujian University of Traditional Chinese MedicineFuzhou 350004China

OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and ***:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular *** effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation *** of apoptosis was performed by flow ***31 levels were examined by *** abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot *** alkali burn was performed on 40 *** were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a *** microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and *** mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein ***:Molecular docking confirmed that emodin was able to target *** findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent *** mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali *** to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated *** dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated ***:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and *** might be a promising new therapeutic option for corneal alkal

关键词： alkali burn emodin corneal inflammation corneal neovascularisation vascular endothelial growth factor receptor-2 signal transduction

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alkali burn injury model of meibomian gland dysfunction in mice

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International Journal of Ophthalmology(English edition) 2024年第12期17卷 2158-2166页

作者： Yong Li Ya-Qiong Yang Yong Lin Ke Yan Yu-Fei Lyu Zhao-Qiang Zhang Cai-Hong Huang Jiao-Yue Hu Zu-Guo Liu Xiamen University Affiliated Xiamen Eye Center Eye Institute of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 3611002Fujian ProvinceChina The Second Affiliated Hospital Hengyang Medical SchoolUniversity of South ChinaHengyang 421000Hunan ProvinceChina Fujian Provincial Key Laboratory of Ophthalmology and Visual Science Fujian Engineering and Research Center of Eye Regenerative MedicineXiamen 3611002Fujian ProvinceChina Department of Traditional Chinese Medicine School of MedicineXiamen UniversityXiamen 361100Fujian ProvinceChina Department of Ophthalmology the First Affiliated Hospital of University of South ChinaHengyang 421001Hunan ProvinceChina

AIM:To establish a stable,short-time,low-cost and reliable murine model of meibomian gland dysfunction(MGD).METHODS:A filter paper sheet soaked in 1.0 mol/L sodium hydroxide(NaOH)solution was used to touch the eyelid margin of C57BL/6J mice for 10s to establish the *** other eye was left untreated as a control *** margin morphological changes and the meibomian glands(MGs)were observed by slit lamp microscopy on days 5 and 10 ***-eosin(HE)staining and Oil red O staining were adopted in detecting the changes in MGs morphology and lipid ***-time polymerase chain reaction,Western blot,immunofluorescence staining and immunohistochemical staining were used to detect interleukin(IL)-6,IL-1β,IL-18,tumor necroses factor(TNF)-α,interferon(IFN)-γ,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4),3-nitroturosine(3-NT),4-hydroxynonenal(4-HNE)and cytokeratin 10(K10)expression changes in ***:MGs showed plugging of orifice,glandular deficiency,abnormal acinar morphology,ductal dilatation,and lipid deposition after alkali *** expressions of IL-6,IL-18,IL-1β,IFN-γ,and TNF-αindicators of inflammation and oxidative stress in MGs tissues were significantly *** keratinization increased in the MG ***:A murine model of MGD is established by alkali burn of the eyelid margin that matches the clinical presentation of MGD providing a stable,short-time,lowcost,and reliable MGD *** new method suggests efficient avenues for future research.

关键词： alkali burn meibomian gland dysfunction animal model oxidative stress

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Effects of AMD3100 subconjunctival injection on alkali burn induced corneal neovascularization in mice

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International Journal of Ophthalmology(English edition) 2011年第1期4卷 44-48页

作者： Liang-Hong Peng, Lin Liu Department of Ophthalmology General Hospital of Guangzhou Military Command of PLA Guangzhou 510010 Guangdong Province China Department of Ophthalmology the First Affiliated Hospital of Second Military Medical University Shanghai 200433 China

AIM: To investigate the therapeutic effects of local and systemic administration of AMD3100 for alkali burn induced corneal neovascularization (CNV) in mice. METHODS: CNV was induced in vivo by alkaline burn of cornea in C57BL/6 mice. AMD3100 was administrated topically by subconjunctival injection or systemically by intraperitoneal injection for 7 days; balanced salt solution was administrated topically or systemically as a control respectively. Inflammatory index was evaluated by slit-lamp biomicroscopy and inflammatory cells infiltrated to cornea tissue were detected by histologic analysis at multiple time points. CNV was compared between the local and systemic treated mice 2 weeks after alkali burn, as quantified by CD34 immunostaining. Fluorescence-Activated Cell Sorter Analysis was used to investigate the mobilizing effects of EPC in mice after subconjunctival injected or intraperitoneal injected AMD3100. Immunohistochemistry was used to detect the expression of endothelial progenitor cells (EPC) marker proteins VEGFR2 and CD34. RESULTS: Three days after alkali burn, infiltration of inflammatory cells was found in corneal tissue. At the first 7 days of local injection group, the number of inflammatory cells was significantly lower than that in systemic injection group. CNV could be seen at the 7(th) day, and at the 14(th) day reached the peak, then started to decrease. The number of CNV in the subconjunctival injection group was 7.57 +/- 1.26 per 0.034mm(2), compared to a number of 14.87 +/- 2.21 per 0.034mm(2) in the control group (P<0.05). On the contrary, the number of CNV in the intraperitoneal injection group was a little higher than that in the control group, 16.34 +/- 1.53 per 0.034mm(2) vs 13.26 +/- 1.87 per 0.034mm(2). The research also showed that intraperitoneally, but not subconjunctivally injected AMD3100 could mobilize EPC. On the other hand, subconjunctival, but not intraperitoneally injected AMD3100 could reduce the expression of EPC marker pro

关键词： alkali burn corneal neovascularization AMD3100 inflammatory cells EPC

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Effect of nintedanib thermo-sensitive hydrogel on neovascularization in alkali burn rat model

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International Journal of Ophthalmology(English edition) 2020年第6期13卷 879-885页

作者： Yan Gong Guo-Hai Wu Ling-Yi Zhang Zhe Zhang Yan-Hong Liao Xiao-Tian Liu Department of Ophthalmology Ningbo Eye HospitalNingbo 315040Zhejiang ProvinceChina

AIM:To investigate the effects of nintedanib thermo-sensitive hydrogel(NTH)on neovascularization and related markers in corneal alkali burns of Wistar ***:NTH was prepared by grinding,and its phase-transition temperature was *** specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups(n=10,each):model group treated with 0.9%saline once a day,NTH group with 0.2%nintedanib b.i.d,and dexamethasone group with dexamethasone ointment once a *** left eye of rats served as the *** corneal transparency was observed under a slit-lamp microscope,and the area of neovascularization was *** day 7,the rats were sacrificed,and the cornea was removed and embedded with paraffin,then stained with hematoxylin一eosin,and the expression of vascular endothelial growth factor receptor 2(VEGFR-2)and CD31 in the corneal tissues of each group was detected by ***:The phase-transition temperature ofnintedanib obtained by grinding was 37℃after adding artificial *** results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group,and the neovascularization area was significantly smaller than that in the model group(Palkali burn in rats.

关键词： nintedanib alkali burn neovascularization cornea rat

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Evaluation of immersion 20 MHz B-scan ultrasonography in observing lens in the alkali burn eyes

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International Journal of Ophthalmology(English edition) 2014年第4期7卷 632-637页

作者： Qing-Hua Yang Bing Chen Li-Qiang Wang Guang-Hua Peng Zhao-Hui Li Yi-Fei Huang Department of Ophthalmology Chinese People's Liberation Army General Hospital

·AIM: To evaluate the accuracy of 20 MHz immersion Bscan ultrasonography in observing lens and to investigate the value of this noninvasive preoperative diagnosis method in alkali burn eyes.·METHODS: It was a comparative study. Fifty-six cases(56 eyes) of alkali burn eyes were examined by ultrasound biomicroscopy(UBM) and immersion 20 MHz B-scan ultrasonography from June 2011 to April 2013,the images were analyzed, and the ultrasonographic diagnosis compared with the operation results.·RESULTS: In 56 alkali burn eyes examined by UBM, the lens were not detected in 16 eyes; the IOL could be detected in 2 eyes; the anterior lens capsule surface or/and the front lens could be detected in 18 eyes, and lens opacification in 3 eyes of them; suspected abnormal lens were detected in the other 20 eyes. In all the same eyes examined by immersion 20 MHz B-scan ultrasonography,the lens were not detected in 16 eyes; the IOL could be detected in 2 eyes; 24 abnormal lens(opacity, lens expansion, shrinkage) and 14 normal lens were *** with the intraoperative findings, the diagnostic accordance rate of the immersion 20 MHz B-scan appearance of lens was 100%(56/56), which was significantly higher than examined by UBM 57.14%(32/56)(χ2=30.55, P =0.0000).·CONCLUSION: Immersion 20 MHz B-scan ultrasonography can observe the lens accurately in alkali burn eyes. It has important clinical value to combine with UBM in eyes of alkali burn.

关键词： immersion B-scan ultrasonography alkali burn ultrasound biomicroscopy

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Changes of uPA and uPA-R expression in the cornea after alkali burn

Changes of uPA and uPA-R expression in the cornea after alka...

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中国细胞生物学学会第八届会员代表大会暨学术大会

作者：严军杨恬李国平张艺曾益军杨进 Department of Cell Biology Third Military Medical University Chongqing 400038 P R China Dept.of Cell Biology Third Military Medical Univ

In order to investigate the expression levels of uPA and uPA-R in corneal repair after alkali burn, we first established the corneal alkali burn models in vitro and in vivo, then we performed immunocytochemistry(ICC) of uPA /uPA-R and image analysis and statistical evaluation to determine their expression levels both in vitro and in vivo. Compared with control group, the expressions of uPA and uPA-R after alkali burn had no significant increases till 6h,then increased rapidly from 12h to 24h and reached their maxima at 24h. From 24h their expression levels decreased rapidly. In vivo they rebounded again after 48 hours and attained their second peaks at 96h respectively. After that, their expressions decreased again. TheuPA-positive reaction mainly distributed in the cytoplasm while that of uPA-R mostly distributed on the cellular membrane. Their expression changes were similar to each other, both in vivo and in vitro. In vivo, uPA and uPA-R expressed and gathereid in the basal layer of corneal epithelium. These results suggest that the time phase of 24h after wound is the typical stage associating with the expressional maximum of uPA and uPA-R both in vivo and in vitro. Furthermore, the results also imply that the expression changes of uPA and uPA-R correlate to the wound healing after the corneal alkali burn, uPA and uPA-R coordinate with each other to stimulate the wound healing.

关键词： uPA uPA-R cornea alkali burn

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Hydrogen promotes the activation of Cu, Zn superoxide dismutase in a rat corneal alkali-burn model

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1173-1179页

作者： Takeshi Arima Tsutomu Igarashi Masaaki Uchiyama Maika Kobayashi Ikuroh Ohsawa Akira Shimizu Hiroshi Takahashi Department of Ophthalmology Nippon Medical SchoolTokyo1138602Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo1138602Japan Biological Process of Aging Tokyo Metropolitan Institute of GerontologyTokyo173-0015Japan

AIM: To investigate the effects of hydrogen(H2) on Cu, Zn superoxide dismutase(SOD1) activation in a rat model of corneal alkali burn. METHODS: In each rat, one cornea was subjected to alkali exposure. Physiological saline(saline group) or H2-dissolved saline(H2 group) was instilled continuously on the cornea for 5 min before and after alkali exposure. Inflammatory cells, neovascularization, and cytoplasmic SOD1 levels were evaluated immunohistochemically in enucleated eyes from both groups. Three-dimensional ultrastructural tissue changes in the eyes were analyzed using low-vacuum scanning electron ***: The numbers of both inflammatory and vascular endothelial cells were significantly reduced in the corneas of the H2 group(P<0.01). Furthermore, H2 treatment increased both cytoplasmic SOD1 levels(P<0.01) and activity in corneal epithelial cells(P<0.01). Notably, the SOD1 activity level in the H2 group was approximately 2.5-fold greater than that in the saline ***: H2 treatment suppresses inflammation and neovascularization in the injured cornea and indirectly suppresses oxidative insult to the cornea by upregulating the SOD1 enzyme protein level and activity.

关键词： hydrogen alkali burn Cu,Zn superoxide dismutase low-vacuum scanning electron microscopy rats

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Efficacy of the nucleotide-binding oligomerization domain 1 inhibitor Nodinhibit-1 on corneal alkali burns in rats

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International Journal of Ophthalmology(English edition) 2015年第5期8卷 860-865页

作者： Xu Huang Yun Han Yi Shao Jing-Lin Yi Affiliated Eye Hospital of Nanchang University Fujian Provincial Key Laboratory of Ophthalmology and Visual Science Eye Institute of Xiamen University Department of Ophthalmology the First Affiliated Hospital of Nanchang University

AIM: To evaluate the therapeutic effect of Nodinhibit-1 on alkali-burn-induced corneal neovascularization (CNV) and inflammation. The nucleotide-binding oligomerzation domain 1 (NOD1) is a potent angiogenic gene. METHODS: The alkali -burned rat corneas (32 right eyes) were treated with eye drops containing Nodinhibit-1 or phosphate buffered solution (PBS, pH 7.4) only, four times per day. CNV and inflammation were monitored using slit lamp microscopy, and the area of CNV was measured by formula. Vascular endothelial growth factor (VEGF) and pigment epithelium -derived factor (PEDF) was determined by Western blot analysis. The TUNEL assay was used to assess the corneal apoptosis cells. RESULTS: alkali-burn-induced progressive CNV and inflammation in the cornea. After treatment for 7d and 14d, there were statistically significant differences in the CNV areas and inflammatory index on that between two group(Palkali burns (Palkali burn -induced CNV and inflammation. The effect of Nodinhibit -1 on CNV may be by regulation the equilibrium of VEGF and PEDF in the wounded cornea.

关键词： Nodinhibit-1 inflammation alkali burn cornea neovascularization

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Therapeutic effects of topical netrin-4 in a corneal acute inflammatory model

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International Journal of Ophthalmology(English edition) 2015年第2期8卷 228-233页

作者： Yun Han Yi Shao Ting-Ting Liu Sang-Ming Li Wei Li Zu-Guo Liu Eye Institute of Xiamen University Fujian Provincial Key Laboratory of Ophthalmology and Visual Science Department of Ophthalmology the First Affiliated Hospital of Nanchang University

AIM: To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned ***: Eye drops containing netrin-4 or phosphate buffered saline(PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp *** specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction(PCR).RESULTS: Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7(P alkali-burn cornea(P alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation.

关键词： netrin-4 inflammation alkali burn cornea

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Effect of vasoactive intestinal peptide on the wound healing of alkali-burned corneas

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International Journal of Ophthalmology(English edition) 2016年第2期9卷 204-210页

作者： Nese Tuncel Nilgun Yildirim Firdevs Gurer Hikmet Basmak Kubilay Uzuner Varol Sahinturk Huseyin Gursoy Department of Physiology Eskisehir Osmangazi University Medical Faculty Eskisehir 26480 Turkey Department of Ophthalmology Eskisehir Osmangazi University Medical Faculty Eskisehir 26480 Turkey Department of Histology Eskisehir Osmangazi University Medical Faculty Eskisehir 26480 Turkey

AIM： To study the effect of vasoactive intestinal peptide （VIP） on wound healing in experimental alkali burns of the cornea. METHODS： Twenty-seven albino rabbits, weighing 3.2 -0.75 kg were used. alkali burns were induced on corneas by applying 10 mm Whatman paper No：50 soaked in 1 mol/L NaOH. They have further classified into 5 groups as follows： 1） control group given no treatment （n=5）; 2） VIP given subconjunctivally （n=6）; 3） VIP injected into anterior chamber （n=6）; 4） NaCI 0.9% given subconjunctivally （n=5）; 5） NaCI 0.9% given into the anterior chamber （n=5）. All treatment protocols except control group were followed by topical eye drops composed of VIP at two hourly intervals for one week from 8 *** to 6 p.m, RESULTS： VIP treated groups of rabbits with alkali burns were found to have better wound healing findings histo-pathologically when compared to those of control group who have received no treatment on day 30. No differences were observed between groups in respect to degree of polymorphonuclear leukocytes （PMNL） infiltration and degree of loss of amorphous substrate on day 15. However, PMNL infiltration and degree of loss of amorphous substrate were lower in Groups 2 and 3 when compared to that of control group on day 30 （P〈0.05）. CONCLUSION： We have shown that VIP has positive effects on alkali induced corneal burns. VIP may inhibit PMNL migration to cornea through an immunomodulatory effect. Inhibition of PMNL migration might reduce the release of collagenaees and this might prevent the extracellular amorphous substance loss.

关键词： vasoactive intestinal peptide alkali-burnedcornea wound healing alkali burn rabbit

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