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Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 297-303页

作者： De-Shuang Li Hong-Xia Liao Jing-Lin Zhang Bo Qin Shenzhen Aier Eye Hospital Aier Eye HospitalJinan UniversityShenzhen 518031Guangdong ProvinceChina Guangzhou Aier Eye Hospital Jinan UniversityGuangzhou 510040Guangdong ProvinceChina

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all Paqueous humor were significantly lower in the combined group than those of the aflibercept group(all P0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone

关键词： diabetic macular edema aqueous humor cytokines aflibercept triamcinolone acetonide

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Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion

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International Journal of Ophthalmology(English edition) 2023年第7期16卷 1041-1046页

作者： Ke-Ke Hu Chao-Wei Tian Man-Hong Li Tong Wu Min Gong Xin-Li Wei Yu-Ru Du Yan-Nian Hui Hong-Jun Du Department of Ophthalmology Eye Institute of PLAXijing HospitalFourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina

AIM:To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy(DR)or retinal vein occlusion(RVO).METHODS:This is a retrospective case control study.The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor(VEGF)for patients diagnosed with macular edema secondary to DR(DME)or RVO(RVO-ME)at Xijing Hospital from August 2021 to July 2022.Meanwhile,aqueous humor samples during vitrectomy from patients with idiopathic macular hole(IMH)were also collected and served as controls.The aqueous humor concentrations of VEGF,platelet-derived factor(PDGF),interleukin(IL)-6,IL-8,IL-18,tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP-1)were measured with Human Premixed Multi-Analyte Kit(Luminex).The difference of the aqueous cytokines and the correlation between the two diseases were analyzed.RESULTS:A total of 40 eyes of 38 patients were enrolled in the study,including 13 eyes of 11 DME patients(DME group),16 eyes of 16 RVO-ME patients(RVO-ME group)and 11 eyes of 11 IMH patients(control group).The VEGF,PDGF,IL-6,IL-8,and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group(all Paqueous humor were significantly higher in the DR group than those in the RVO group(all Paqueous humor of eyes with two diseases.CONCLUSION:Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME,the roles of these factors are more significant or more likely to be activated in DR patients,suggesting different treatment strategies should be considered for the two diseases.

关键词： macular edema diabetic retinopathy retinal vein occlusion cytokines aqueous humor

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Changes of total antioxidant capacity and total oxidant status of aqueous humor in diabetes patients and correlations with diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2013年第4期6卷 531-536页

作者： Emrullah Beyazyildiz Ali Bülent ankaya Esra Ergan Mustafa Alparslan Anayol Yasemin zdamar Sevilay Sezer Mehmet Hakan Tirhis Pelin Yilmazbas Faruk ztürk Department of Ophthalmology Gazi Mustafa Kemal State HospitalAnkara 06900Turkey Department of Ophthalmology Ulucanlar Eye Research and Training HospitalAnkara 06900Turkey Department of Ophthalmology Van Government HospitalVanAnkara 06900Turkey Department of Biochemistry Numune Research and Training HospitalAnkara 06900Turkey

AIM:To measure changes of total oxidant status(TOS)and total antioxidant capacity(TAC) of aqueous humor(AH) in diabetic retinopathy(DR) patients,and to determine if there were any differences in TOS and TAC of AH in diabetic patients without retinopathy compared with non-diabetic patients.·METHODS:One hundred and three eyes of 103patients who were enrolled for cataract surgery were included in this study.Patients were grouped according to presence of diabetes and stage of DR.Prior to cataract surgery,0.1mL to 0.2mL of AH was aspirated and analyzed for TAC and TOS level using a colorimetric method.·RESULTS:TOS levels were highest among proliferative diabetic retinopathy(PDR) patients and lowest in patients with only cataracts.Results were statistically significant between all groups(P aqueous humor TAC levels are low in diabetic patients and reduced further in DR patients,TOS levels are increased in diabetic patients and this is exacerbated in DR patients.

关键词： aqueous humor diabetic retinopathy total antioxidant capacity total oxidant status

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LMWH inhibits anterior chamber inflammation after extra capsular lens extraction through down regulation of bFGF content in aqueous humor

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International Journal of Ophthalmology(English edition) 2012年第4期5卷 430-433页

作者： Jian-Ming Wang Lei Xiong Quan-Chen Xiong and Ya-Zhi Fan Department of Ophthalmology the Second Affiliated Hospital Medical School of Xi'an Jiaotong University Xi'an 710004 Shaanxi Province China

AIM: To observe the changes of basic fibroblast growth factor (bFGF) content in anterior chamber before and after extra capsular lens extraction for investigating the mechanism of low molecular weight heparin (LMWH) inhibiting anterior chamber inflammation. METHODS: Eighty-four rabbits were randomly divided into control and experimental group, 42 rabbits in each group. Extra capsular lens extraction was done on unilateral eye in each rabbit. LMWH was perfused into anterior chamber by the concentration of 50U/mL at the end of operation in experimental group. The degrees of corneal edema, aqueous flare and fibrin were evaluated with slit lamp microscope in postoperative day 1, 3, 6, 15, 30, 45 and 60, respectively. Six eyes of each group were at each time point. Contents of bFGF in aqueous humor were determined by ELISA after animals were killed. Another six eyes were used for determining the base line level of bFGF in aqueous humor. RESULTS: The degrees of corneal edema, aqueous flare and fibrin in experimental group were significantly lighter than those in control group (paqueous humor increased at the same time. bFGF content was reached peal on postoperative day 1 in experimental group, while on postoperative day 6 in control group. Contents of bFGF in the two groups declined slowly after reaching peak. The bFGF content in control group were significantly higher than that in experimental group 1-30 days after surgery (paqueous humor.

关键词： low molecular weight heparin inflammation aqueous humor basic fibroblast growth factor extracapsular lens extraction

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Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus

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International Journal of Ophthalmology(English edition) 2016年第5期9卷 721-724页

作者： Erdinc Aydin Semsettin Sahin Izmir Katip Celebi University Faculty of MedicineOphthalmology Gaziosmanpasa University Faculty of Medicine Biochemistry

AIM： To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy（DR） grade in type 2 diabetic patients.·METHODS： aqueous humor and plasma samples from26 patients with DR（in nonproliferative and proliferative stages） and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme-linked immunosorbent assay（ELISA）.·RESULTS： Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy（PDR） [18.57 ±2.67 pg/m L（range 15.20-23.06）vs 13.63±2.71 pg/m L（range 10.20-20.20）, P =0.0001], but not in those with nonproliferative retinopathy（NPDR）[13.79±2.56 pg/m L（range 9.80-20.10） vs 13.63±2.71 pg/m L（range 10.20-20.20）, P =0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [ 5. 37 ±1.74 pg/m L（range 2.85-8.65） vs 6.11±1.90 pg/m L（range3.13-9.41）, P =0.293], or between control and DR groups[NPDR 6.11 ±1.90 pg/m L（range 3.13-9.41） vs control6.15±1.91 pg/m L（range 2.18-9.86）; PDR（5.37±1.74 pg/m L（range 2.85-8.65） vs control 6.15 ±1.91 pg/m L（range2.18-9.86）, P =0.808, P =0.264].·CONCLUSION： Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity.

关键词： aqueous humor diabetes mellitus diabetic retinopathy melatonin

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Pharmacokinetics of recombinant human basic fibroblast growth factor in rabbits and mice serum and rabbits aqueous humor

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Acta Pharmacologica Sinica 2004年第8期 17-21页

作者： Qi ZHANG, Guang-ji WANG, Jian-guo SUN Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

AIM: To study the pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in rabbits and mice after iv and postocular administration, and the changes of rhbFGF in rabbits aqueous humor after postocular administration. METHODS: After iv or postocular administration three doses of rhbFGF in rabbits and mice, rhbFGF concentration in serum and rabbit aqueous humor was determined by enzyme-linked immunosorbent assay. RESULTS: Serum concentration-time data of rabbits after iv administration of rhbFGF 1, 2, and 4 μg/kg were fitted to bi-exponential equations with half-lives of 0.9, 0.9, and 0.6 min for T1/2α and 7, 8, and 4.7 min for T1/2β. Plasma concentration-time data of mice after iv administration of rhbFGF 2.5, 5 and 10 μg/kg were fitted to bi exponential equations with half-lives of 0.4, 0.6, and 0.9 min for T1/2α　and 6, 5, and 7 min for T1/2β.The AUCs were linearly correlated to doses in both cases (rrabbit=0.997, rmouse=0.999). The serum concentrations of rhbFGF were very l

关键词： fibroblast growth factor 2 pharmacokinetics enzyme-linked immunosorbent assay aqueous humor rabbits mice

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MicroRNAs as biomarkers in glaucoma and potential therapeutic targets

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Neural Regeneration Research 2022年第11期17卷 2368-2375页

作者： Bridget Martinez Philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Glaucoma is a neurodegenerative disease in which optic nerve damage and visual field defects occur.It is a leading cause of irreversible blindness.Its pathogenesis is largely unknown although several risk factors have been identified,with an increase in intraocular pressure being the main one.Lowering of intraocular pressure is the only treatment available.Open-angle glaucoma is the most common form of the condition,accounting for~90%of all cases of glaucoma,with primary open-angle glaucoma and exfoliation glaucoma being the most frequent types.There are strong indications that microRNAs play important roles in the pathogenesis of primary open-angle glaucoma.Most of the recent studies reviewed had performed microRNA profiling in aqueous humor from glaucoma patients compared to controls who were chiefly cataract patients.A very large number of microRNAs were dysregulated but with limited overlap between individual studies.MiRNAs in aqueous humor that could be possible targets for therapeutic intervention are miR-143-3p,miR-125b-5p,and miR-1260b.No ove rlap of findings occurred within the dysregulated miRNAs for blood plasma,blood serum,peripheral blood mononuclear cells,and tears of primary open-angle glaucoma patients.Seve ral impo rtant limitations were identified in these studies.Further studies are warranted of mic roRNA expression in aqueous humor and blood samples of primary open-angle glaucoma patients in the early stages of the disease so that validated biomarkers can be identified and treatment initiated.In addition,whether modifying the levels of specific microRNAs in aqueous humor or tears has a beneficial effect on intraocular pressure and ophthalmic examination of the eyes should be investigated using suitable animal models of glaucoma.

关键词： aqueous humor biomarkers blood plasma blood serum glaucoma intraocular pressure microRNA peripheral blood mononuclear cells tears therapeutic targets

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Real-time and label-free biosensing using moiré pattern generated by bioresponsive hydrogel

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生物活性材料(英文) 2023年第5期23卷 383-393页

作者： Semin Kim Geehong Kim Yong Woo Ji Chae-Eun Moon Yuna Jung Hyung Keun Lee JaeJong Lee Won-Gun Koh Department of Chemical and Biomolecular Engineering Yonsei University50 Yonsei-roSeodaemun-guSeoul120-749Republic of Korea Korea Institute of Machinery&Materials Nano-Convergence Mechanical Systems Research Division156 Gajeongbuk-roYuseong-guDaejeon34103Republic of Korea Department of Ophthalmology Yongin Severance HospitalYonsei University College of Medicine363Dongbaekjukjeon-daeroGiheung-guYongin-siGyeonggi-do16995Republic of Korea Institute of Vision Research Department of OphthalmologyYonsei University College of Medicine50-1 Yonsei-roSeodaemun-guSeoul120-749Republic of Korea Department of Ophthalmology Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineRepublic of Korea College of Pharmacy Yonsei University85 Songdo Hwawak-roYeonsu-guIncheon26426Republic of Korea Department of Ophthalmology Gangnam Severance HospitalYonsei University College of Medicine211 Eonju-roGangnam-guSeoul06273Republic of Korea Department of Nanomechatronics University of Science and Technology217Gajeong-roYuseong-guDaejeon 34113Republic of Korea

Bioresponsive hydrogels are smart materials that respond to various external stimuli and exhibit great potential as biosensors owing to their capability of real-time and label-free detection.Here,we propose a sensing platform based on bioresponsive hydrogels,employing the concept of moiré patterns.Two sets of line patterns with different pitch sizes are prepared;a hydrogel grating whose pitch size changes according to external stimuli and a reference grating with constant pitch size.The volume changes of the hydrogel caused by external stimuli changes the pitch size of the hydrogel grating,and subsequently,the pitch sizes of the moiré patterns(moiré signal),whose values can be obtained in a real-time and label-free manner through customized moiré microscopy and signal processing.After confirming that the pH-induced swelling of hydrogel could be monitored using moiré patterns,we performed moiré pattern-based detection of specific proteins using protein-responsive hydrogel that underwent shrinking via interaction with target proteins.Brain-derived neurotrophic factor and platelet-derived growth factor were selected as the model proteins,and our proposed system successfully detected both proteins at nanomolar levels.In both cases,the pitch size change of hydrogel grating was monitored much more sensitively using moiré patterns than through direct measurements.The changes in the moiré signals caused by target proteins were detected in ex-vivo environments using a custom-made intraocular lens incorporating the hydrogel grating,demonstrating the capability of the proposed system to detect various markers in intraocular aqueous humor,when implanted in the eye.

关键词： Bioresponsive hydrogel Moirépattern Biosensing Intraocular lens aqueous humor

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Risk factors for the long-term prognosis and recurrence of HIV-negative cytomegalovirus retinitis in North China

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International Journal of Ophthalmology(English edition) 2022年第10期15卷 1634-1640页

作者： Yan-Hong Shi Hui Wang Hao Kang Jing Feng Xiao-Feng Hu Yun Li Zhu-Yun Qian Yong Tao Department of Ophthalmology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Zhantansi Outpatient Department Jing Zhong Medical AreaChinese PLA General HospitalBeijing 100853China Beijing GIANTMED Medical Diagnostics Lab Beijing 101300China

AIM: To demonstrate the clinical features, the risk factors, the visual prognosis and the recurrence of cytomegalovirus(CMV) retinitis(CMVR) in HIV-negative patients.METHODS: HIV-negative patients with CMVR were involved in this study. Best corrected visual acuity(BCVA), intraocular pressure(IOP), CMV-DNA load in aqueous and/or serum samples, treatment, follow-up time, recurrence and complications were recorded. Ocular characteristics were evaluated by fundus photographs. Association between ocular factors and visual prognosis were analyzed by regression analysis.RESULTS: Twenty-five eyes of 16 patients were included. All 25 eyes underwent intravitreal injections of anti-viral agents. The mean log MAR BCVA improved from 0.94±0.98(0.98-0.78) initially to 0.77±0.73(0.82-0.68) at last visit, but not significantly. After antiviral treatment, the aqueous CMV DNA load significantly reduced to(3.42±1.47)×10~2 copies/m L(P=0.001), compared with(2.51±3.11)×10~5 copies/m L at baseline. Macular involvement(R~2=0.475, P=0.049) and initial visual acuity(R~2=0.475, P=0.017) were significantly associated with the poor visual prognosis(BCVA<20/400). The extent of retinal lesions(R~2=0.064, P=0.04) was significant associated with the risk of recurrence of CMVR.CONCLUSION: Intravitreal injection of anti-viral agents offers a safe and effective treatment for CMVR. Macular involvement and initial visual acuity significantly associate with visual prognosis. The extent of retinal lesions is significantly associated with the recurrence of CMVR. These ocular factors can be used as predictive risk factors for long term visual prognosis in HIV-negative CMVR patients.

关键词： cytomegalovirus retinitis aqueous humor visual acuity risk factors recurrence

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Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation

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International Journal of Ophthalmology(English edition) 2022年第3期15卷 388-393页

作者： Koichi Yoshida Motofumi Kawai Tsugiaki Utsunomiya Akihiro Ishibazawa Young-Seok Song Mariana Sayuri BUdo Yoshikazu Tasaki Akitoshi Yoshida Department of Ophthalmology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan Department of Hospital Pharmacy&Pharmacology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan

AIM: To investigate changes in extracellular matrix(ECM) gene expression in human trabecular meshwork(HTM) cells in response to mechanical fluid flow stimulation.METHODS: HTM cells were grown on a glass plate coated with 0.02% type Ⅰ collagen(COL) and exposed to shear stress(0, 0.2, 1.0 dyne/cm;) for 12 h.Changes in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain reaction.Phosphorylation of Smad2 protein was investigated by Western blotting.RESULTS: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control(Paqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

关键词： trabecular meshwork shear stress aqueous humor extracellular matrix glaucoma intraocular pressure

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