Objective To evaluate nitric oxide(NO)and vascular endothelial growth factor(VEGF)in vitreous humor and blood samples in patients with proliferative diabetic retinopathy(PDR)and in patients with branch retinal vein oc...Objective To evaluate nitric oxide(NO)and vascular endothelial growth factor(VEGF)in vitreous humor and blood samples in patients with proliferative diabetic retinopathy(PDR)and in patients with branch retinal vein occlusion(BRVO).Methods NO concentrations were determined by using the Greiss reaction in plasma and vitreous humor samples.VEGF levels were assayed by ELISA.The patients in the studies were divided into four groups:16 patients with PDR,5 patients with BRVO,11 patients with rhegmatogenous retinal detachment(RRD),and 10 patients with idiopathic macular hole(IMH).Results The vitreous fluid levels of NO were significantly higher in patients with PDR(15.2μmol/L,4.6-50.9μmol/L)than those in the other three groups(F=5.13,P=0.005).The concentrations of VEGF were significantly higher in patients with PDR and BRVO(1507.2 μg/mL,50.71-3722.0μg/ml;838.8μg/mL,159.6-3328.0μg/mL)than those in the other two groups(F=6.84,P=0.0008),but highest in PDR(T=3.92,P=0.001).There was no significant difference between NO and VEGF in serum in four groups.There was no correlation between concentrations of NO and VEGF in four groups whatever in vitreous or plasma(all P>0.05).Conclusion The results suggest that higher levels of NO and VEGF may be related to the angiogenesis in DR.展开更多
Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for ra- re genetic disorders is perhaps the most extreme form of personalized medicine, in that th...Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for ra- re genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients＇ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation（s） underlying disease. In this review, we discuss the application of Next Generation Sequencing （NGS） to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases： Leber＇s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt＇s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinforrnatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine.展开更多
基金Supported by Shanghai Leading Academic Discipline Project(S30205)Shanghai Science and Technology Commission Foundation(08JC1415600)National Natural Science Foundation of China(60978030)
文摘Objective To evaluate nitric oxide(NO)and vascular endothelial growth factor(VEGF)in vitreous humor and blood samples in patients with proliferative diabetic retinopathy(PDR)and in patients with branch retinal vein occlusion(BRVO).Methods NO concentrations were determined by using the Greiss reaction in plasma and vitreous humor samples.VEGF levels were assayed by ELISA.The patients in the studies were divided into four groups:16 patients with PDR,5 patients with BRVO,11 patients with rhegmatogenous retinal detachment(RRD),and 10 patients with idiopathic macular hole(IMH).Results The vitreous fluid levels of NO were significantly higher in patients with PDR(15.2μmol/L,4.6-50.9μmol/L)than those in the other three groups(F=5.13,P=0.005).The concentrations of VEGF were significantly higher in patients with PDR and BRVO(1507.2 μg/mL,50.71-3722.0μg/ml;838.8μg/mL,159.6-3328.0μg/mL)than those in the other two groups(F=6.84,P=0.0008),but highest in PDR(T=3.92,P=0.001).There was no significant difference between NO and VEGF in serum in four groups.There was no correlation between concentrations of NO and VEGF in four groups whatever in vitreous or plasma(all P>0.05).Conclusion The results suggest that higher levels of NO and VEGF may be related to the angiogenesis in DR.
基金Jacques Zaneveld is supported by NIH training grant T32 EY007102Chen Rui is supported by grants from the Retinal Research Foundation and National Eye Institute (R01EY018571,R01EY022356)
文摘Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for ra- re genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients＇ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation（s） underlying disease. In this review, we discuss the application of Next Generation Sequencing （NGS） to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases： Leber＇s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt＇s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinforrnatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine.
