Systemic Administration of Erythropoietin Inhibits Retinopathy in RCS Rats

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Aug 15

PMID 25119659

Citations 16

Authors

Weiyong Shen

Sook H Chung

Mohammad R Irhimeh

Shiying Li

So-Ra Lee

Mark C Gillies

Affiliations

Soon will be listed here.

Abstract

Objective: Royal College of Surgeons (RCS) rats develop vasculopathy as photoreceptors degenerate. The aim of this study was to examine the effect of erythropoietin (EPO) on retinopathy in RCS rats.

Methods: Fluorescein angiography was used to monitor retinal vascular changes over time. Changes in retinal glia and vasculature were studied by immunostaining. To study the effects of EPO on retinal pathology, EPO (5000 IU/kg) was injected intraperitoneally in 14 week old normal and RCS rats twice a week for 4 weeks. Changes in the retinal vasculature, glia and microglia, photoreceptor apoptosis, differential expression of p75 neurotrophin receptor (p75NTR), pro-neurotrophin 3 (pro-NT3), tumour necrosis factor-α (TNFα), pigment epithelium derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A), the production of CD34(+) cells and mobilization of CD34(+)/VEGF-R2(+) cells as well as recruitment of CD34(+) cells into the retina were examined after EPO treatment.

Results: RCS rats developed progressive capillary dropout and subretinal neovascularization which were accompanied by retinal gliosis. Systemic administration of EPO stabilized the retinal vasculature and inhibited the development of focal vascular lesions. Further studies showed that EPO modulated retinal gliosis, attenuated photoreceptor apoptosis and p75NTR and pro-NT3 upregulation, promoted the infiltration of ramified microglia and stimulated VEGF-A expression but had little effect on TNFα and PEDF expression. EPO stimulated the production of red and white blood cells and CD34(+) cells along with effective mobilization of CD34(+)/VEGF-R2(+) cells. Immunofluorescence study demonstrated that EPO enhanced the recruitment of CD34+ cells into the retina.

Conclusions: Our results suggest that EPO has therapeutic potentials in treatment of neuronal and vascular pathology in retinal disease. The protective effects of EPO on photoreceptors and the retinal vasculature may involve multiple mechanisms including regulation of retinal glia and microglia, inhibition of p75NTR-pro-NT3 signaling together with stimulation of production and mobilization of bone marrow derived cells.

Citing Articles

Quantification of microvascular change of retinal degeneration in Royal College of Surgeons rats using high-resolution spectral domain optical coherence tomography angiography.

Zhang Z, Wu Y, Chien Y, Chen Y, Chiou S, Chen S J Biomed Opt. 2023; 28(10):106001.

PMID: 37841506 PMC: 10570624. DOI: 10.1117/1.JBO.28.10.106001.

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy.

Fu X, Feng S, Qin H, Yan L, Zheng C, Yao K Front Mol Neurosci. 2023; 16:1100254.

PMID: 36756614 PMC: 9899825. DOI: 10.3389/fnmol.2023.1100254.

Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote Pro-survival Gene Expression and Protect Photoreceptors From Sodium Iodate-Induced Cytotoxicity in a Retinal Degeneration Model.

Koh A, Alsaeedi H, Rashid M, Lam C, Nizam Harun M, Ng M Front Cell Dev Biol. 2021; 9:652017.

PMID: 33987180 PMC: 8111290. DOI: 10.3389/fcell.2021.652017.

Dorsal-Ventral Differences in Retinal Structure in the Pigmented Royal College of Surgeons Model of Retinal Degeneration.

Greferath U, Huynh M, Jobling A, Vessey K, Venables G, Surrao D Front Cell Neurosci. 2021; 14:553708.

PMID: 33536874 PMC: 7848141. DOI: 10.3389/fncel.2020.553708.

Longitudinal Structural and Microvascular Observation in RCS Rat Eyes Using Optical Coherence Tomography Angiography.

Tan B, Barathi V, Lin E, Ho C, Gan A, Yao X Invest Ophthalmol Vis Sci. 2020; 61(6):54.

PMID: 32579681 PMC: 7415900. DOI: 10.1167/iovs.61.6.54.

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