A Hypothesis: Can Erythropoietin Administration Affect the Severity of Retinopathy in Diabetic Patients With Renal Failure?

Diskin, Charles J.; Stokes, Thomas J.; Dansby, Linda M.; Radcliff, Lautrec; Carter, Thomas B.

doi:10.1097/maj.0b013e3180a5e8ed

Cited by 28 publications

(20 citation statements)

References 15 publications

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“…A similar effect of EPO on accelerating the decline of kidney function had been suggested by earlier studies (33). Furthermore, prevalence and severity of PDR have worsened with increased EPO dosing (34). Recent work indicates that administration of EPO early in retinal vascular development protects retinal neuron and vasculature, whereas administration of EPO during retinal capillary nonperfusion associated with hypoxia markedly worsens retinal neovascularization in OIR mice (35).…”

Section: Discussionmentioning

confidence: 56%

Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications

Tong

Yang

Patel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

183

191

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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 ؋ 10 ؊3 ; Genetics of Kidneys in Diabetes (GoKinD) Study: P ‫؍‬ 2.66 ؋ 10 ؊8 ; and Boston: P ‫؍‬ 2.1 ؋ 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. diabetic microvascular complication ͉ end stage renal disease ͉ proliferative diabetic retinopathy ͉ SNP ͉ association

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Section: Discussionmentioning

confidence: 56%

Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications

Tong

Yang

Patel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

183

191

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“…Spanish commercial presentations recommended start with a dosage of 0.5 once a week and titrated it every month following clinical response [79]. Other commercial recommendations for initiation of therapy are dosages of 0.25 mg twice a week and increased it by 0.25 mg twice weekly up to a dosage of 1 mg twice a week according to the patient's serum prolactin level [80]. In the last years, there is important concerns about cardiovascular side-effecs of the treatment of Parkinson's Disease with cabergoline and other dopamine agonist [81].…”

Section: Limitations Of the Resultsmentioning

confidence: 99%

Safety of Cabergoline in the Management of Pituitary Prolactin-Induced Symptoms with Patients Treated with Atypical Neuroleptics

Coronas¹,

Cobo

Giménez-Palop³

et al. 2012

CDS

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“…However, the effects that synthetic erythropoietin can have on the progression of diabetic retinopathy has not been completely established. Some authors defend that administration of erythropoietin increases the risk of proliferative retinopathy [86,87]. Even so, in a mouse model of retinopathy, a protective effect of erythropoietin has been described [88].…”

Section: Erythropoietinmentioning

confidence: 99%

Diabetic Retinopathy: Understanding Pathologic Angiogenesis and Exploring its Treatment Options

Falcão¹

2012

TOCVJ

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Diabetic retinopathy is the major cause of blindness at working age. The pathogenesis behind visual loss is related with retinal angiogenesis and increased retinal vascular permeability. These changes seem to be the result of chronic hyperglycemia and hypoxia. Several mechanisms have been proposed to cause the retinal and vasculature cellular damage. They include the formation of advanced end glycation products, aldose reductase activity and reactive oxygen species. Ultimately, they lead to the expression of VEGF-A. This growth factor seems to play the pivotal role in the development of the complications associated with the disease including break down of the inner blood retinal barrier, macular edema and vasoproliferation. Other mechanisms like inflammation, protein kinase C activity and erythropoietin have been strongly associated with the pathogenesis.Laser therapy is still the standard of care for diabetic retinopathy and prevents severe vision loss in 95% of patients if timely treatment is performed. The better understanding of the disease has led to the production of new management options that may become important adjuvants for the disease. They include intravitreal anti-VEGF therapy, intravitreal steroid therapy and systemic protein kinase C inhibitors. Vitrectomy is an important option for advanced cases of the disease such as tractional retinal detachment or non-absorbing vitreous hemorrhages.

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A Hypothesis: Can Erythropoietin Administration Affect the Severity of Retinopathy in Diabetic Patients With Renal Failure?

Cited by 28 publications

References 15 publications

Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications

Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications

Safety of Cabergoline in the Management of Pituitary Prolactin-Induced Symptoms with Patients Treated with Atypical Neuroleptics

Diabetic Retinopathy: Understanding Pathologic Angiogenesis and Exploring its Treatment Options

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