To report the case of a patient who presented with idiopathic choroidal neovascularization(CNV)as the first sign of multiple evanescent white dot syndrome(MEWDS).A 25-year-old woman presented with recent onset of decr...To report the case of a patient who presented with idiopathic choroidal neovascularization(CNV)as the first sign of multiple evanescent white dot syndrome(MEWDS).A 25-year-old woman presented with recent onset of decreased vision and metamorphopsia in the right eye.The results of fundoscopic examination,fluorescein angiography,and optical coherence tomography(OCT) were compatible with a diagnosis of idiopathic CNV,which was treated with one intravitreal injection of bevacizumab.Five years later,the patient returned complaining of photopsia and decreased vision in the same eye.The fundoscopic examination showed typical signs of MEWDS.After 3 months,recurrence of CNV was observed in the same eye.In conclusion,idiopathic CNV might be the only manifestation of a subclinical occurrence of MEWDS.In this case,it was followed by a recurrence of MEWDS and subsequent reactivation of CNV.展开更多
Background:To investigate the effect of sirolimus(SRL)eye drops on acute alkali-burn-induced corneal neovascularization(CNV)and explore its possible mechanism.Methods:A total of 57 male Sprague-Dawley rats weighing 16...Background:To investigate the effect of sirolimus(SRL)eye drops on acute alkali-burn-induced corneal neovascularization(CNV)and explore its possible mechanism.Methods:A total of 57 male Sprague-Dawley rats weighing 160-180 g were randomly divided into four groups including a normal control group(NC group,n=12),an untreated alkali-burned model control group(MC group,n=15),a blank eye drop treatment group(BT group,n=15),and an SRL eye drop treatment group(ST group,n=15).Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3,7,and 14 days after alkali exposure.Three rats were randomly sacrificed in each group before modeling and 3,7,14 days after modeling,and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.Results:Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC,BT,and ST groups 1 day after alkali exposure but were alleviated at day 3.The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7(F=9.77,P<0.05)and 14(F=5.81,P<0.05).At day 1,the corneal limbal vascular network was markedly filled.SNV was obvious at days 3,7,and 14.The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups,and the CNV scores showed significant differences among these groups(day 3:F=8.60,P<0.05;day 7:F=11.40,P<0.05;and day 14:F=41.59,P<0.01).Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups(F=0.52,P>0.05;F=0.98,P>0.05).The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3,7,and 14 days after alkali exposure,and there were significant differences in relative gray-scale values among these groups(day 3:F=32.16,P<0.01;day 7:F=85.96,P<0.01;day 14:F=57.68,P<0.01).The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3,7,and 14,and there were significant differences in relative gray-scale values among groups(day 3:F=32.16,P<0.01;day 7:F=53.02,P<0.01;day 14:F=38.67,P<0.01).Conclusions:SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models.It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue,which may contribute to the inhibition of alkali-burn-induced CNV.展开更多
Background:We investigated the role of beta-adrenergic receptor(B-AR)on choroidal neovascularization(CNV)in an animal model of age-related macular degeneration in mice.Methods:The angiogenic effect of the B-AR was eva...Background:We investigated the role of beta-adrenergic receptor(B-AR)on choroidal neovascularization(CNV)in an animal model of age-related macular degeneration in mice.Methods:The angiogenic effect of the B-AR was evaluated in retinal pigment epithelium(RPE)-choroid explants from C57Bl6 mice stimulated with propranolol or isoproterenol(10μM)(respectively antagonist and agonist of the B-AR)during 24 h.Conversely,a classic choroidal neovascularization(CNV)model induced by laser burn in C57Bl6 mice(8 weeks)was used to assess the anti-angiogenic effect of propranolol.In this experiment,mice were treated with intraperitoneal propranolol(6 mg/kg/d)or vehicle(saline solution)daily for 10 days,starting on day 4 after laser burn and until sacrifice(day 14).Immunostaining analysis on retinal flatmounts and cryosections were performed to determine the surface of CNV,the distribution of B-AR and the number and morphology of microglia/macrophages associated with CNV.To explore if the antiangiogenic effect of propranolol involved the modulation of the inflammatory microenvironment associated with CNV,we used RPE primary cells,J774 macrophages cell line and polarized M1 and M2 bone marrow-derived macrophage(BMDM).Choroidal explants treated with conditioned media(CM)from J774 or polarized M1/M2 BMDM pre-treated with propranolol to confirm the anti-angiogenic effect of propranolol.Expression of angiogenic factors was evaluated by RT PCR and Elisa.Results:The expression and distribution of the B-1,B-2 and B-3 adrenergic receptors were localized in the choroid and RPE cells.The stimulation of RPE-choroid explants with isoproterenol increased CNV compared to vehicle,while propranolol decreased CNV.In vivo,propranolol inhibited significantly the levels of VEGF and CNV growth in laser burn model compared to the vehicle.Additionally,the treatment with propranolol decremented the number of activated(amoeboid shape)microglia/macrophages but surprisingly,the number of non-activated microglia/macrophages around the CNV was higher than with the vehicle treatment.In vitro,propranolol modulated the angiogenic balance in macrophages promoting anti-angiogenic factors expression,especially with M2 BMDM.CM from macrophages pre-treated with propranolol reduced CNV on choroidal explants.Conclusions:These ex vivo and in vivo studies highlight the importance of B-adrenergic receptor in the CNV.Propranolol can inhibit CNV by decreasing the levels of VEGF and modulating microglia/macrophages activation.Further work will investigate the role of B-adrenergic receptor on suppression of the inflammatory environment in order to understand the link between neovascularization and inflammation in CNV during age-related macular degeneration.展开更多
In developed countries,age-related macular degeneration(AMD)is the main cause of visual impairment in the elderly.Though the etiology of AMD is still unclear,it has been well understood that vascular endothelial growt...In developed countries,age-related macular degeneration(AMD)is the main cause of visual impairment in the elderly.Though the etiology of AMD is still unclear,it has been well understood that vascular endothelial growth factor(VEGF)is involved in the development of aberrant vasculature that represents the neovascular AMD(nAMD).Hence,VEGF inhibition is a more effective way to control nAMD.Pegaptanib,ranibizumab,and aflibercept are three drugs approved by the US Food and Drug Administration(FDA)to treat nAMD.Bevacizumab(an anti-VEGF medication comparable to ranibizumab)is already widely used off label.Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies.Synthetic designed ankyrin repeat proteins(DARPins)imitate antibodies introduced recently by evolutions in bioengineering technology.These agents are designed to have high specificity and affinity to a specific target,smaller molecular size,and better tissue penetration,making them more stable and longer-acting at less concentration.Abicipar pegol(Allergan,Dublin,Ireland)is a DARPin that interlocks all VEGF-A isoforms.It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab,making it a feasible anti-VEGF agent.This review describes the properties and efficacy of abicipar,the new anti-VEGF agent,in clinical practice,which aims to improve outcomes,safety,and treatment burden of nAMD.展开更多
文摘To report the case of a patient who presented with idiopathic choroidal neovascularization(CNV)as the first sign of multiple evanescent white dot syndrome(MEWDS).A 25-year-old woman presented with recent onset of decreased vision and metamorphopsia in the right eye.The results of fundoscopic examination,fluorescein angiography,and optical coherence tomography(OCT) were compatible with a diagnosis of idiopathic CNV,which was treated with one intravitreal injection of bevacizumab.Five years later,the patient returned complaining of photopsia and decreased vision in the same eye.The fundoscopic examination showed typical signs of MEWDS.After 3 months,recurrence of CNV was observed in the same eye.In conclusion,idiopathic CNV might be the only manifestation of a subclinical occurrence of MEWDS.In this case,it was followed by a recurrence of MEWDS and subsequent reactivation of CNV.
基金Supported by the Guangdong Natural Science Foundation(2016A030313294).
文摘Background:To investigate the effect of sirolimus(SRL)eye drops on acute alkali-burn-induced corneal neovascularization(CNV)and explore its possible mechanism.Methods:A total of 57 male Sprague-Dawley rats weighing 160-180 g were randomly divided into four groups including a normal control group(NC group,n=12),an untreated alkali-burned model control group(MC group,n=15),a blank eye drop treatment group(BT group,n=15),and an SRL eye drop treatment group(ST group,n=15).Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3,7,and 14 days after alkali exposure.Three rats were randomly sacrificed in each group before modeling and 3,7,14 days after modeling,and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.Results:Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC,BT,and ST groups 1 day after alkali exposure but were alleviated at day 3.The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7(F=9.77,P<0.05)and 14(F=5.81,P<0.05).At day 1,the corneal limbal vascular network was markedly filled.SNV was obvious at days 3,7,and 14.The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups,and the CNV scores showed significant differences among these groups(day 3:F=8.60,P<0.05;day 7:F=11.40,P<0.05;and day 14:F=41.59,P<0.01).Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups(F=0.52,P>0.05;F=0.98,P>0.05).The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3,7,and 14 days after alkali exposure,and there were significant differences in relative gray-scale values among these groups(day 3:F=32.16,P<0.01;day 7:F=85.96,P<0.01;day 14:F=57.68,P<0.01).The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3,7,and 14,and there were significant differences in relative gray-scale values among groups(day 3:F=32.16,P<0.01;day 7:F=53.02,P<0.01;day 14:F=38.67,P<0.01).Conclusions:SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models.It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue,which may contribute to the inhibition of alkali-burn-induced CNV.
文摘Background:We investigated the role of beta-adrenergic receptor(B-AR)on choroidal neovascularization(CNV)in an animal model of age-related macular degeneration in mice.Methods:The angiogenic effect of the B-AR was evaluated in retinal pigment epithelium(RPE)-choroid explants from C57Bl6 mice stimulated with propranolol or isoproterenol(10μM)(respectively antagonist and agonist of the B-AR)during 24 h.Conversely,a classic choroidal neovascularization(CNV)model induced by laser burn in C57Bl6 mice(8 weeks)was used to assess the anti-angiogenic effect of propranolol.In this experiment,mice were treated with intraperitoneal propranolol(6 mg/kg/d)or vehicle(saline solution)daily for 10 days,starting on day 4 after laser burn and until sacrifice(day 14).Immunostaining analysis on retinal flatmounts and cryosections were performed to determine the surface of CNV,the distribution of B-AR and the number and morphology of microglia/macrophages associated with CNV.To explore if the antiangiogenic effect of propranolol involved the modulation of the inflammatory microenvironment associated with CNV,we used RPE primary cells,J774 macrophages cell line and polarized M1 and M2 bone marrow-derived macrophage(BMDM).Choroidal explants treated with conditioned media(CM)from J774 or polarized M1/M2 BMDM pre-treated with propranolol to confirm the anti-angiogenic effect of propranolol.Expression of angiogenic factors was evaluated by RT PCR and Elisa.Results:The expression and distribution of the B-1,B-2 and B-3 adrenergic receptors were localized in the choroid and RPE cells.The stimulation of RPE-choroid explants with isoproterenol increased CNV compared to vehicle,while propranolol decreased CNV.In vivo,propranolol inhibited significantly the levels of VEGF and CNV growth in laser burn model compared to the vehicle.Additionally,the treatment with propranolol decremented the number of activated(amoeboid shape)microglia/macrophages but surprisingly,the number of non-activated microglia/macrophages around the CNV was higher than with the vehicle treatment.In vitro,propranolol modulated the angiogenic balance in macrophages promoting anti-angiogenic factors expression,especially with M2 BMDM.CM from macrophages pre-treated with propranolol reduced CNV on choroidal explants.Conclusions:These ex vivo and in vivo studies highlight the importance of B-adrenergic receptor in the CNV.Propranolol can inhibit CNV by decreasing the levels of VEGF and modulating microglia/macrophages activation.Further work will investigate the role of B-adrenergic receptor on suppression of the inflammatory environment in order to understand the link between neovascularization and inflammation in CNV during age-related macular degeneration.
文摘In developed countries,age-related macular degeneration(AMD)is the main cause of visual impairment in the elderly.Though the etiology of AMD is still unclear,it has been well understood that vascular endothelial growth factor(VEGF)is involved in the development of aberrant vasculature that represents the neovascular AMD(nAMD).Hence,VEGF inhibition is a more effective way to control nAMD.Pegaptanib,ranibizumab,and aflibercept are three drugs approved by the US Food and Drug Administration(FDA)to treat nAMD.Bevacizumab(an anti-VEGF medication comparable to ranibizumab)is already widely used off label.Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies.Synthetic designed ankyrin repeat proteins(DARPins)imitate antibodies introduced recently by evolutions in bioengineering technology.These agents are designed to have high specificity and affinity to a specific target,smaller molecular size,and better tissue penetration,making them more stable and longer-acting at less concentration.Abicipar pegol(Allergan,Dublin,Ireland)is a DARPin that interlocks all VEGF-A isoforms.It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab,making it a feasible anti-VEGF agent.This review describes the properties and efficacy of abicipar,the new anti-VEGF agent,in clinical practice,which aims to improve outcomes,safety,and treatment burden of nAMD.
