Abstract
OBJECTIVES:Erythropoietin may have neuroprotective potential after ischemia of the central nervous system. Here, we conducted a study to characterize the protective effects of erythropoietin on retinal ganglion cells and gliotic reactions in an experimentally induced oligemia model.METHODS:Rats were subjected to global oligemia by bilateral common carotid artery occlusion and then received either vehicle or erythropoietin via intravitreal injection after 48 h; they were euthanized one week after the injection. The densities of retinal ganglion cells and contents of glial fibrillary acidic protein (astrocytes/Müller cells) and cluster of differentiation 68 clone ED1 (microglia/macrophages), assessed by fluorescence intensity, were evaluated in frozen retinal sections by immunofluorescence and epifluorescence microscopy.RESULTS:Retinal ganglion cells were nearly undetectable one week after oligemia compared with the sham controls; however, these cells were partially preserved in erythropoietin-treated retinas. The contents of glial fibrillary acidic protein and cluster of differentiation 68 clone ED1, markers for reactive gliosis, were significantly higher in retinas after bilateral common carotid artery occlusion than those in both sham and erythropoietin-treated retinas.CONCLUSIONS:The number of partially preserved retinal ganglion cells in the erythropoietin-treated group suggests that erythropoietin exerts a neuroprotective effect on oligemic/ischemic retinas. This effect could be related to the down-modulation of glial reactivity, usually observed in hypoxic conditions, clinically observed during glaucoma or retinal artery occlusion conditions. Therefore, glial reactivity may enhance neurodegeneration in hypoxic conditions, like normal-tension glaucoma and retinal ischemia, and erythropoietin is thus a candidate to be clinically applied after the detection of decreased retinal blood flow.
Highlights
Erythropoietin (EPO) is a glycoprotein secreted in response to hypoxia that stimulates the differentiation and proliferation of erythrocyte progenitor cells and may have additional physiological effects as a cytokine with antiapoptotic, neurotrophic, angiogenic and antioxidant roles [1,2,3,4]
Ten days after the rats were subjected to oligemia, retinas of both the bilateral common carotid artery occlusion (BCCAO) and phosphate buffered saline (PBS) groups showed reduced thickness compared with that of the sham group, and both plexiform layers appeared to be disorganized (Figure 1 A-C)
Compared with that in the sham group, brain-specific homeobox/POU domain protein 3A (Brn3a) labeling revealed a significant loss of RGCs in both the BCCAO and the PBS groups (Figure 1E-G) and labeling of a considerable number of cells after EPO administration (Figure 1H)
Summary
Erythropoietin (EPO) is a glycoprotein secreted in response to hypoxia that stimulates the differentiation and proliferation of erythrocyte progenitor cells and may have additional physiological effects as a cytokine with antiapoptotic, neurotrophic, angiogenic and antioxidant roles [1,2,3,4]. The neuroprotective potential of EPO has been described in several animal models of central nervous system (CNS) injury. No potential conflict of interest was reported. Received for publication on May 8, 2017. Accepted for publication on November 27, 2017
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