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: 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.
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Authors | Weiyong Shen, Sook H Chung, Mohammad R Irhimeh, Shiying Li, So-Ra Lee, Mark C Gillies |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 8
Pg. e104759
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25119659
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptor, Nerve Growth Factor
- Tumor Necrosis Factor-alpha
- Erythropoietin
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Topics |
- Animals
- Apoptosis
(drug effects)
- Blotting, Western
- Diabetic Retinopathy
(prevention & control)
- Erythropoietin
(administration & dosage, pharmacology)
- Flow Cytometry
- Fluorescein Angiography
- Fluorescent Antibody Technique
- Image Processing, Computer-Assisted
- In Situ Nick-End Labeling
- Neuroglia
(drug effects)
- Rats
- Rats, Mutant Strains
- Receptor, Nerve Growth Factor
(metabolism)
- Retina
(cytology, drug effects)
- Retinal Vessels
(drug effects)
- Tumor Necrosis Factor-alpha
(metabolism)
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