ABSTRACT
Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case-control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P = 1.91 x 10(-3); Genetics of Kidneys in Diabetes (GoKinD) Study: P = 2.66 x 10(-8); and Boston: P = 2.1 x 10(-2)]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications.
Subject(s)
Diabetic Nephropathies/complications , Diabetic Nephropathies/genetics , Diabetic Retinopathy/complications , Diabetic Retinopathy/genetics , Erythropoietin/genetics , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics , Alleles , Animals , Cell Line , Cohort Studies , Erythropoietin/metabolism , Gene Expression Regulation , Genes, Reporter , Genetic Predisposition to Disease , Haplotypes , Humans , Kidney/metabolism , Kidney/pathology , Luciferases/metabolism , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , Retina/metabolism , Retina/pathologyABSTRACT
PURPOSE: To report the recurrent bullous retinal detachments as complications of photodynamic therapy (PDT) for idiopathic polypoidal choroidal vasculopathy (IPCV). DESIGN: Interventional case report. METHODS: A pseudophakic 84-year-old-woman had IPCV and decreased vision. Angiography demonstrated macular leakage. PDT with verteporfin was applied. Two days later, visual acuity decreased from 20/50 to 20/400. Examination revealed extensive inferior subretinal fluid, which mimicked a pseudophakic rhegmatogenous retinal detachment. A scleral buckle was placed; no retinal breaks were identified. RESULTS: Vision and fluid resolved over three weeks. Four months later, examination revealed decreased vision and persistent leakage. Two days after repeat PDT, bullous exudative macular detachment recurred. Detachment resolved over two weeks; visual acuity returned to 20/50. CONCLUSION: IPCV that is treated with PDT may be complicated by iatrogenic bullous exudative retinal detachments that resemble rhegmatogenous detachments. Modified treatment parameters may reduce the risk of recurrence. The natural history likely includes spontaneous resolution and visual recovery.
