Erythropoietin in diabetic retinopathy

Reid, Gerard; Lois, Noemi

doi:10.1016/j.visres.2017.05.010

Cited by 23 publications

(24 citation statements)

References 65 publications

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“…These data correspond to recent publications, where most elevated serum Epo concentration was determined along with more advanced stages of diabetic retinopathy, like in work of Semeraro, Mustafa and Reida (44,45,46). Moustafa et al compared vitreous and serum levels of Epo, as well as their correspondence with certain Epo gene, and their results are in accordance with our study report, where bigger concentrations of Epo in the eye and in serum were correlating with PDR forms of DR.…”

Section: Discussionsupporting

confidence: 92%

Systemic Erythropoietin Concentration and its Correlation with Stage of Diabetic Retinopathy

Davidović

Babić

Jovanović

et al. 2019

Preprint

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Summary: Background: Erythropoietin (Epo) is one of systemic angiogenic factors, and its role in ocular angiogenesis and in diabetic retinopathy (DR) is not yet fully understood. Latest research data reveal possible correlation of higher EPO concentrations of erythropoietin in blood and in the eye, with more severe of stages of DR. The main aim of this work was to examine the possible influence of serum concentrations of erythropoietin on the development and stages of diabetic retinopathy in patients with diabetes mellitus type 2. Methods: The research involved 90 patients examined at University Eye Clinic in Clinical Center of Vojvodina in Novi Sad, Serbia. First group comprised of 60 patients with diabetes mellitus lasting 10 years or more, with diabetic retinopathy. Second, control group, consisted of 30 healthy individuals. In the first group of 60 diabetic patients, 30 of them had non-proliferative diabetic retinopathy (NPDR), and 30 had proliferative diabetic retinopathy (PDR). Laboratory EPO serum levels were determined, and they were correlated to the stage of DR. Concentration of EPO was assessed by ELISA method at the end of the study. Results: The highest average concentration of EPO in serum (9.95 mIU/ml) was determined in group of diabetics with PDR. The lowest average concentration of EPO in serum (6.90 mIU/ml) was found in control group. The average concentration of Epo in serum in group of diabetics with NPDR was 7.00 mIU/ml. EPO concentration in serum was elevated in group of PDR, and it was directly proportional to the level of clinical stadium of PDR, being significantly higher in moderate and severe subgroup of PDR comparing to control healthy subjects, NPDR and mild PDR (h=9.858, p=0.007). Conclusions: Significantly elevated serum concentration of EPO in advanced stages of DR, and positive correlation between EPO serum concentration and clinical stadium of PDR, suggest that erythropoietin presents one of the important growth factors from blood, which plays role in retinal ischemia and angiogenesis in diabetic retinopathy, especially in the proliferative stage of this disease. Keywords: diabetic retinopathy; erythropoietin; glycated hemoglobin; non-proliferative diabetic retinopathy; proliferative diabetic retinopathy.

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Section: Discussionsupporting

confidence: 92%

Systemic Erythropoietin Concentration and its Correlation with Stage of Diabetic Retinopathy

Davidović

Babić

Jovanović

et al. 2019

Preprint

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“…Endothelin-1 (ET-1), upregulated in the retina of patients with diabetes, is also an alternative target for prevention of neurodegeneration in diabetic retinopathy (118). ET-1 has dual deleterious actions on microvessels and neurons caused by its capacity to bind to endothelin receptors A (ETA) which mainly mediate vasoconstriction and vascular degeneration and B (ETB), involved in retinal neurodegeneration (119).…”

Section: Treatment/prevention Of Neurodegenerationmentioning

confidence: 99%

“…Neuroprotective effects of intravitreal erythropoietin injections have been seen through anti-apoptotic, antioxidant, and anti-inflammatory actions in animal models (122,(124)(125)(126). Systemic use of erythropoietin has been associated with side effects including hypertension and increased risk of thrombosis, thus early, small clinical trials have investigated intravitreal delivery of recombinant EPO (118). In a small FDA phase 1a safety and tolerability trial, intravitreal erythropoietin (Procrit) in five eyes of five patients that were unresponsive to prior surgery, laser, steroid and anti-VEGF demonstrated a logMAR 0.3 or more significant improvement in chart acuity and central field acuity perimetry, with clearing of exudates, but little change in leakage defined by fluorescein angiography at 16 weeks ongoing injection and follow-up (127).…”

Section: Treatment/prevention Of Neurodegenerationmentioning

confidence: 99%

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Sinclair

Schwartz

2019

Front. Endocrinol.

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Diabetes mellitus is a world-wide epidemic and diabetic retinopathy, a devastating, vision-threatening condition, is one of the most common diabetes-specific complications. Diabetic retinopathy is now recognized to be an inflammatory, neuro-vascular complication with neuronal injury/dysfunction preceding clinical microvascular damage. Importantly, the same pathophysiologic mechanisms that damage the pancreatic β-cell (e.g., inflammation, epigenetic changes, insulin resistance, fuel excess, and abnormal metabolic environment), also lead to cell and tissue damage causing organ dysfunction, elevating the risk of all complications, including diabetic retinopathy. Viewing diabetic retinopathy within the context whereby diabetes and all its complications arise from common pathophysiologic factors allows for the consideration of a wider array of potential ocular as well as systemic treatments for this common and devastating complication. Moreover, it also raises the importance of the need for methods that will provide more timely detection and prediction of the course in order to address early damage to the neurovascular unit prior to the clinical observation of microangiopathy. Currently, treatment success is limited as it is often initiated far too late and after significant neurodegeneration has occurred. This forward-thinking approach of earlier detection and treatment with a wider array of possible therapies broadens the physician's armamentarium and increases the opportunity for prevention and early treatment of diabetic retinopathy with preservation of good vision, as well the prevention of similar destructive processes occurring among other organs.

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“…Cibinetide, also known as ARA 290 and helix B surface peptide (HBSP), is a synthetic 11 amino acid peptide, derived from the structure of the B helix of EPO, with marked anti-apoptotic, anti-inflammatory and anti-permeability effects, recapitulating the effects of the endogenous EPO [ 9 , 10 , 11 ]. Unlike EPO, is not haematopoietic and, thus, is free of the possible side effects of EPO, which can be life threatening (reviewed by Reid and Lois) [ 12 ]. In an experimental model of DR, cibinetide administered systemically inhibited vascular leakage and edema [ 10 ] and protected against retinal blood vessel and neuroglial degeneration [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema

Lois

Gardner

McFarland

et al. 2020

JCM

Self Cite

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Purpose: Evaluating the effects of cibinetide in diabetic macular edema (DME). Methods: Phase 2 trial. Naïve patients with >400 µm central retinal thickness (CRT) DME in one/both eyes were recruited (May 2016–April 2017) at the Belfast Health and Social Care Trust. The study eye was that with best vision and lowest CRT. Patients self-administered cibinetide 4 mg/day subcutaneously for 12 weeks. Primary and secondary outcomes: mean change from baseline to week 12 in best corrected visual acuity (BCVA), CRT, central retinal sensitivity, tear production, patient-reported outcomes, adverse events and antibodies to cibinetide. Descriptive statistics were used; exploratory analyses focused on non-study eyes, diabetic control, serum cytokines and albuminuria. Results: Nine patients were recruited; eight completed the study. There was no improvement in mean change baseline-week 12 in BCVA (−2.9 + 5.0), CRT (10 + 94.6 microns), central retinal sensitivity (−0.53 + 1.9 dB) or tear production (−0.13 + 7.7 mm), but there was an improvement in National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite scores (2.7 + 3.1). Some participants experienced improvements in CRT, tear production, diabetic control and albuminuria. No serious adverse events/reactions or anti-cibinetide antibodies were seen. Conclusions: The cibinetide 12-week course was safe. Improvements in NEI VFQ-25 scores, CRT, tear production, diabetic control and albuminuria, observed in some participants, warrant further investigation. Trial Registration: EudraCT number: 2015-001940-12. ISRCTN16962255—registration date 25.06.15.

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Erythropoietin in diabetic retinopathy

Cited by 23 publications

References 65 publications

Systemic Erythropoietin Concentration and its Correlation with Stage of Diabetic Retinopathy

Systemic Erythropoietin Concentration and its Correlation with Stage of Diabetic Retinopathy

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema

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