AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2)thin films(PSF)with different degrees of opacity as IOL materi...AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2)thin films(PSF)with different degrees of opacity as IOL materials were prepared.The light transmission of the PSF-IOL was measured,and its in vitro biosafety was determined by cell counting kit(CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line.Subsequently,the in vivo safety was determined by implanting the PSF-IOL with 10%wt SiO_(2)into the right eyes of New Zealand white rabbits(PSF-IOL group),and compared with two control groups:contralateral comparison group and normal control(NC)group(Contralateral comparison group:the fellow eye;NC group:a group of binocular normal rabbits without intervention).The flash visual-evoked potentials(F-VEPs)were measured to verify amblyopia.RESULTS:PSFs containing 0,2%,and 10%wt SiO_(2)were successfully constructed.The 0 SiO_(2)PSF was transparent,while the 10%wt SiO_(2)PSF was completely opaque.It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro.In vitro,PSF-IOL with 10%wt SiO_(2)was also non-toxic,and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation.Finally,our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia.CONCLUSION:A PSF-IOL that mimics cataracts is created.A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit.It can be developed fast and stable and holds great potential for future study.展开更多
Background The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene(MMACHC)c.482G>A mutation in 195 Chinese ca...Background The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene(MMACHC)c.482G>A mutation in 195 Chinese cases with CblC disease.Methods We carried out a national,retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G>A variant either in a homozygous or compound heterozygous state.The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G>A mutation.Clinical features,including disease onset,symptoms,biochemical metabolites,gene mutation,and follow-up outcomes were reviewed and analyzed in detail.The median follow-up period spanned 3 years and 8 months,with a range of 1 year and 2 months to 12 years and 10 months.Results Among 195 patients carrying the c.482G>A variant,125(64.1%)cases were diagnosed by newborn screening(NBS),60(30.8%)cases were detected due to disease onset,and 10(5.1%)cases were identified from sibling diagnoses.One hundred and seventeen(93.6%)individuals who were diagnosed by NBS,and nine patients who came from sibling diagnoses remained asymptomatic in this study.From 69 symptomatic patients of the c.482G>A group,more patients presented with later onset,and the top six common clinical symptoms at disease onset were developmental delay(59.4%),lower limb weakness and poor exercise tolerance(50.7%),cognitive decline(37.7%),gait instability and abnormal posture(36.2%),seizures(26.1%),and psychiatric and behavioral disturbances(24.6%).In the 159 symptomatic patients lacking c.482G>A variants,the most frequently observed clinical manifestations at disease onset included developmental delay(81.8%),lethargy and feeding difficulty(62.9%),lower limb weakness and poor exercise tolerance(54.7%),prolonged neonatal jaundice(51.6%),vomiting(47.2%),and seizures(32.7%).Before treatment,the levels of blood propionylcarnitine,propionylcarnitine/acetylcarnitine ratio,and homocysteine in the c.482G>A group were significantly lower(P<0.05)than those in the non-c.482G>A group,while the concentration of urinary methylmalonic acid was slightly lower(P>0.05).The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels(P<0.05).In patients carrying the c.482G>A variant compared with the non-c.428G>A group,there were markedly lower rates of mortality(0.5%vs.2.0%)and developmental delay(20.5%vs.65.5%).When compared with individuals diagnosed due to disease onset,those identified through NBS in either group exhibited a reduced proportion of disease onset(6.7%vs.100%in the c.482G>A group,54.4%vs.100%in the non-c.482G>A group),lower mortality(0.0%vs.1.7%in the c.482G>A group,0.0%vs.3.6%in the non-c.482G>A group),and had a higher percentage of patients exhibiting normal psychomotor and language development(99.3%vs.33.3%in the c.482G>A group,58.9%vs.10.9%in the non-c.482G>A group).Conclusions The c.482G>A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease.Patients with this mutation tend to have a relatively better response to hydroxocobalamin,better metabolic control,and more favorable neurological outcomes.NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis,resulting in favorable clinical outcomes.展开更多
基金Supported by National Natural Science Foundation of China(No.81870680).
文摘AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2)thin films(PSF)with different degrees of opacity as IOL materials were prepared.The light transmission of the PSF-IOL was measured,and its in vitro biosafety was determined by cell counting kit(CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line.Subsequently,the in vivo safety was determined by implanting the PSF-IOL with 10%wt SiO_(2)into the right eyes of New Zealand white rabbits(PSF-IOL group),and compared with two control groups:contralateral comparison group and normal control(NC)group(Contralateral comparison group:the fellow eye;NC group:a group of binocular normal rabbits without intervention).The flash visual-evoked potentials(F-VEPs)were measured to verify amblyopia.RESULTS:PSFs containing 0,2%,and 10%wt SiO_(2)were successfully constructed.The 0 SiO_(2)PSF was transparent,while the 10%wt SiO_(2)PSF was completely opaque.It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro.In vitro,PSF-IOL with 10%wt SiO_(2)was also non-toxic,and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation.Finally,our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia.CONCLUSION:A PSF-IOL that mimics cataracts is created.A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit.It can be developed fast and stable and holds great potential for future study.
基金funded by the Scientific research Project Plan of Shanghai Municipal Health Commission(No.202140346)the National Key Research and Development Program of China(No.2016YFC0901505).
文摘Background The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene(MMACHC)c.482G>A mutation in 195 Chinese cases with CblC disease.Methods We carried out a national,retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G>A variant either in a homozygous or compound heterozygous state.The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G>A mutation.Clinical features,including disease onset,symptoms,biochemical metabolites,gene mutation,and follow-up outcomes were reviewed and analyzed in detail.The median follow-up period spanned 3 years and 8 months,with a range of 1 year and 2 months to 12 years and 10 months.Results Among 195 patients carrying the c.482G>A variant,125(64.1%)cases were diagnosed by newborn screening(NBS),60(30.8%)cases were detected due to disease onset,and 10(5.1%)cases were identified from sibling diagnoses.One hundred and seventeen(93.6%)individuals who were diagnosed by NBS,and nine patients who came from sibling diagnoses remained asymptomatic in this study.From 69 symptomatic patients of the c.482G>A group,more patients presented with later onset,and the top six common clinical symptoms at disease onset were developmental delay(59.4%),lower limb weakness and poor exercise tolerance(50.7%),cognitive decline(37.7%),gait instability and abnormal posture(36.2%),seizures(26.1%),and psychiatric and behavioral disturbances(24.6%).In the 159 symptomatic patients lacking c.482G>A variants,the most frequently observed clinical manifestations at disease onset included developmental delay(81.8%),lethargy and feeding difficulty(62.9%),lower limb weakness and poor exercise tolerance(54.7%),prolonged neonatal jaundice(51.6%),vomiting(47.2%),and seizures(32.7%).Before treatment,the levels of blood propionylcarnitine,propionylcarnitine/acetylcarnitine ratio,and homocysteine in the c.482G>A group were significantly lower(P<0.05)than those in the non-c.482G>A group,while the concentration of urinary methylmalonic acid was slightly lower(P>0.05).The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels(P<0.05).In patients carrying the c.482G>A variant compared with the non-c.428G>A group,there were markedly lower rates of mortality(0.5%vs.2.0%)and developmental delay(20.5%vs.65.5%).When compared with individuals diagnosed due to disease onset,those identified through NBS in either group exhibited a reduced proportion of disease onset(6.7%vs.100%in the c.482G>A group,54.4%vs.100%in the non-c.482G>A group),lower mortality(0.0%vs.1.7%in the c.482G>A group,0.0%vs.3.6%in the non-c.482G>A group),and had a higher percentage of patients exhibiting normal psychomotor and language development(99.3%vs.33.3%in the c.482G>A group,58.9%vs.10.9%in the non-c.482G>A group).Conclusions The c.482G>A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease.Patients with this mutation tend to have a relatively better response to hydroxocobalamin,better metabolic control,and more favorable neurological outcomes.NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis,resulting in favorable clinical outcomes.
