AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characte...AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases.METHODS:DL-AAA(80 mmol/L)was administered IVT into both eyes of Dutch Belted rabbit.Post DL-AAA delivery,clinical ophthalmic examinations were performed weekly following modified Mc Donald-Shadduck Scoring System.Color fundus photography,fluorescein angiography(FA),and optical coherence tomography(OCT)procedures were performed every 2 or 4 wk until stable retinal vascular leakage was observed.Once stable retinal leakage(12 wk post DL-AAA administration)was established,anti-vascular endothelial growth factor(VEGF)(bevacizumab,ranibizumab and aflibercept)and anti-inflammatory(triamcinolone,TAA)drugs were tested for their efficacy after IVT administration.Fluorescein angiograms were scored before and after treatment following a novel grading system,developed for the DL-AAA rabbit model.RESULTS:Post DL-AAA administration,eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor.Retinal hemorrhage was restricted to the tips of neo-retinal vessels.FA revealed maximum retinal vascular leakage at 2 wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12.Retinal vascular angiographic and tomographic features were stable and consistent up to 36 mo among two different staggers induced for RNV at two different occasions.Day 7,mean FA scores showed that 1μg/eye of bevacizumab,ranibizumab,aflibercept and 2μg/eye of TAA suppress 65%,90%,100%and 50%retinal vascular leakage,respectively.Day 30,bevacizumab and TAA continued to show 66%and 44%suppression while ranibizumab effect was becoming less effective(68%).In contrast,aflibercept was still able to fully(100%)suppress vascular leakage on day 30.On day 60,bevacizumab,ranibizumab and TAA showed suppression of 7%,12%,and 9%retinal vascular leakage,respectively,however,aflibercept continued to be more effective showing 50%suppression of vascular leakage.CONCLUSION:The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage.Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations,alone or in combination with anti-inflammatory compounds.展开更多
Background Photodynamic therapy （PDT） has been recommended as a main treatment for idiopathic choroidal neovascularization （I-CNV）.But the visual results of PDT were inconsistent and variable,and PDT may bring sev...Background Photodynamic therapy （PDT） has been recommended as a main treatment for idiopathic choroidal neovascularization （I-CNV）.But the visual results of PDT were inconsistent and variable,and PDT may bring severe damage to the retinal pigment epithelium and choriocapillaries.In recent years,intravitreal ranibizumab therapy,showing favorable visual outcomes,has developed as an advanced treatment for choroidal neovascularization （CNV）.Although both methods have been reported to be effective in treating I-CNV,there is no detailed comparative report between the two methods.This study aimed to compare visual outcomes,retinal and choroidal thickness between intravitreal ranibizumab therapy and PDT in the treatment of I-CNV,and investigate the correlation of visual outcomes with retinal and choroidal thickness in each of the two groups.Methods Thirty-seven eyes of 37 patients with I-CNV were involved in this study; 19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were treated with PDT.The best corrected visual acuity （BCVA） was recorded before and at each follow-up visit after treatments （IogMAR）.Enhanced-depth imaging optical coherence tomography （EDI-OCT） was used to evaluate the retinal structural changes,and to measure central retinal thickness （CRT） and central choroidal thickness （CCT）.Results Mean BCVA was 0.64±0.27 in PDT group and 0.69±0.22 in ranibizumab group at baseline （P=0.55）.When compared with the baseline,mean BCVA in PDT group was improved significantly at 3-month after PDT （0.41±0.16,P=0.002）,then changed little （0.42±0.25 at 12-month,P=0.88）.Whereas mean BCVA in Ranibizumab group was improved significantly at each follow-up visit.It improved much more obviously in the first month and then remained stable.The mean BCVA in the ranibizumab group was significantly better at each follow-up visit than that in PDT （P ＜0.05）.When compared with the baseline,mean CRT in PDT group decreased significantly since 3-month visit,whereas mean CRT in ranibizumab group decreased significantly from 1-month visit.Mean CRT at 1-month and 3-month decreased much more in ranibizumab group than that in PDT group,almost in the same period as BCVA improving.When compared with the baseline,mean CCT did not change significantly at each follow-up visit in each group （P ＞0.05）.The CCT difference was not statistically significant between the two groups at each same time visit （P ＞0.05）.Mean BCVA was correlated with CRT,but was not correlated with CCT.Conclusions Both intravitreal ranibizumab therapy and PDT are effective for the treatment of I-CNV.It is obvious that ranibizumab therapy is significantly superior to PDT in improving BCVA and decreasing CRT.CRT decreases much more rapidly in ranibizumab group than in PDT group,simultaneously with visual improvement.CRT reduction has significant correlation with the visual outcomes in the recovery of I-CNV,whereas BCVA prognosis may have no correlation with CCT.CCT is not changed significantly after each of the treatments.Both PDT and ranibizumab therapy may have no significant effect on choroid.展开更多
Long noncoding RNA(lncRNA)regulates the proliferation and migration of human retinal endothelial cells,as well as retinal neovascularization in diabetic retinopathy.Based on similarities between the pathogenesis of re...Long noncoding RNA(lncRNA)regulates the proliferation and migration of human retinal endothelial cells,as well as retinal neovascularization in diabetic retinopathy.Based on similarities between the pathogenesis of retinopathy of prematurity(ROP)and diabetic retinopathy,lncRNA may also play a role in ROP.Seven-day-old mice were administered 75±2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP model.Expression of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology,and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The results showed that compared with the control group,57 lncRNAs were differentially expressed,including 43 upregulated and 14 downregulated,in the retinal tissue of ROP mice.Compared with control mice,42 mRNAs were differentially expressed in the retinal tissue of ROP mice,including 24 upregulated and 18 downregulated mRNAs.Differentially expressed genes were involved in ocular development and related metabolic pathways.The differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling pathways.Our results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP treatment.This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25,2016(approval No.2016PS074K).展开更多
文摘AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases.METHODS:DL-AAA(80 mmol/L)was administered IVT into both eyes of Dutch Belted rabbit.Post DL-AAA delivery,clinical ophthalmic examinations were performed weekly following modified Mc Donald-Shadduck Scoring System.Color fundus photography,fluorescein angiography(FA),and optical coherence tomography(OCT)procedures were performed every 2 or 4 wk until stable retinal vascular leakage was observed.Once stable retinal leakage(12 wk post DL-AAA administration)was established,anti-vascular endothelial growth factor(VEGF)(bevacizumab,ranibizumab and aflibercept)and anti-inflammatory(triamcinolone,TAA)drugs were tested for their efficacy after IVT administration.Fluorescein angiograms were scored before and after treatment following a novel grading system,developed for the DL-AAA rabbit model.RESULTS:Post DL-AAA administration,eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor.Retinal hemorrhage was restricted to the tips of neo-retinal vessels.FA revealed maximum retinal vascular leakage at 2 wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12.Retinal vascular angiographic and tomographic features were stable and consistent up to 36 mo among two different staggers induced for RNV at two different occasions.Day 7,mean FA scores showed that 1μg/eye of bevacizumab,ranibizumab,aflibercept and 2μg/eye of TAA suppress 65%,90%,100%and 50%retinal vascular leakage,respectively.Day 30,bevacizumab and TAA continued to show 66%and 44%suppression while ranibizumab effect was becoming less effective(68%).In contrast,aflibercept was still able to fully(100%)suppress vascular leakage on day 30.On day 60,bevacizumab,ranibizumab and TAA showed suppression of 7%,12%,and 9%retinal vascular leakage,respectively,however,aflibercept continued to be more effective showing 50%suppression of vascular leakage.CONCLUSION:The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage.Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations,alone or in combination with anti-inflammatory compounds.
基金This study was supported by grants from the National Natural Science Foundation of China （No.81272981） and Natural Sciences Fundation of Beijing,China （No.7112031）.
文摘Background Photodynamic therapy （PDT） has been recommended as a main treatment for idiopathic choroidal neovascularization （I-CNV）.But the visual results of PDT were inconsistent and variable,and PDT may bring severe damage to the retinal pigment epithelium and choriocapillaries.In recent years,intravitreal ranibizumab therapy,showing favorable visual outcomes,has developed as an advanced treatment for choroidal neovascularization （CNV）.Although both methods have been reported to be effective in treating I-CNV,there is no detailed comparative report between the two methods.This study aimed to compare visual outcomes,retinal and choroidal thickness between intravitreal ranibizumab therapy and PDT in the treatment of I-CNV,and investigate the correlation of visual outcomes with retinal and choroidal thickness in each of the two groups.Methods Thirty-seven eyes of 37 patients with I-CNV were involved in this study; 19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were treated with PDT.The best corrected visual acuity （BCVA） was recorded before and at each follow-up visit after treatments （IogMAR）.Enhanced-depth imaging optical coherence tomography （EDI-OCT） was used to evaluate the retinal structural changes,and to measure central retinal thickness （CRT） and central choroidal thickness （CCT）.Results Mean BCVA was 0.64±0.27 in PDT group and 0.69±0.22 in ranibizumab group at baseline （P=0.55）.When compared with the baseline,mean BCVA in PDT group was improved significantly at 3-month after PDT （0.41±0.16,P=0.002）,then changed little （0.42±0.25 at 12-month,P=0.88）.Whereas mean BCVA in Ranibizumab group was improved significantly at each follow-up visit.It improved much more obviously in the first month and then remained stable.The mean BCVA in the ranibizumab group was significantly better at each follow-up visit than that in PDT （P ＜0.05）.When compared with the baseline,mean CRT in PDT group decreased significantly since 3-month visit,whereas mean CRT in ranibizumab group decreased significantly from 1-month visit.Mean CRT at 1-month and 3-month decreased much more in ranibizumab group than that in PDT group,almost in the same period as BCVA improving.When compared with the baseline,mean CCT did not change significantly at each follow-up visit in each group （P ＞0.05）.The CCT difference was not statistically significant between the two groups at each same time visit （P ＞0.05）.Mean BCVA was correlated with CRT,but was not correlated with CCT.Conclusions Both intravitreal ranibizumab therapy and PDT are effective for the treatment of I-CNV.It is obvious that ranibizumab therapy is significantly superior to PDT in improving BCVA and decreasing CRT.CRT decreases much more rapidly in ranibizumab group than in PDT group,simultaneously with visual improvement.CRT reduction has significant correlation with the visual outcomes in the recovery of I-CNV,whereas BCVA prognosis may have no correlation with CCT.CCT is not changed significantly after each of the treatments.Both PDT and ranibizumab therapy may have no significant effect on choroid.
基金supported by the National Natural Science Foundation of China,No.81600747(to YD)Startup Foundation for Doctors of Liaoning Province,China,No.201501020(to YD)
文摘Long noncoding RNA(lncRNA)regulates the proliferation and migration of human retinal endothelial cells,as well as retinal neovascularization in diabetic retinopathy.Based on similarities between the pathogenesis of retinopathy of prematurity(ROP)and diabetic retinopathy,lncRNA may also play a role in ROP.Seven-day-old mice were administered 75±2% oxygen for 5 days and normoxic air for another 5 days to establish a ROP model.Expression of lncRNA and mRNA in the retinal tissue of mice was detected by high-throughput sequencing technology,and biological functions of the resulted differentially expressed RNAs were evaluated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The results showed that compared with the control group,57 lncRNAs were differentially expressed,including 43 upregulated and 14 downregulated,in the retinal tissue of ROP mice.Compared with control mice,42 mRNAs were differentially expressed in the retinal tissue of ROP mice,including 24 upregulated and 18 downregulated mRNAs.Differentially expressed genes were involved in ocular development and related metabolic pathways.The differentially expressed lncRNAs may regulate ROP in mice via microRNAs and multiple signaling pathways.Our results revealed that these differentially expressed lncRNAs may be therapeutic targets for ROP treatment.This study was approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University on February 25,2016(approval No.2016PS074K).
