Abstract
ObjectiveRoyal 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.MethodsFluorescein 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.ResultsRCS 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.ConclusionsOur 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.
Highlights
Neuro-vascular degeneration and neovascularization are features of many retinal diseases such as diabetic retinopathy, inherited retinal degenerations and retinopathy of prematurity [1,2,3]
In order to study further the therapeutic mechanisms underlying EPO treatment for retinal diseases, we examined the effect of EPO on retinal capillary dropout and pathological neovascularization in Royal College of Surgeons (RCS) rats
We examined changes in retinal vascular density to determine whether EPO treatment prevented retinal capillary dropout (Figure 4)
Summary
Neuro-vascular degeneration and neovascularization are features of many retinal diseases such as diabetic retinopathy, inherited retinal degenerations and retinopathy of prematurity [1,2,3]. The earliest signs of diabetic retinopathy are associated with regional failure of retinal microvascular function, including loss of pericytes and vascular endothelial cells, blood-retinal barrier breakdown, microaneurysms and intraretinal haemorrhages [2,4]. These vascular abnormalities can lead to macular oedema, retinal ischemia and neovascularization without treatment. Regardless of its cause, one way to reduce the risk of blindness from retinal neovascularization is to prevent the retinal vasculopathy that precedes and causes it
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
