Neuroprotective effects of erythropoietin on rat retinas subjected to oligemia

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.

Synthetic Polyclonal-Derived CDR Peptides as an Innovative Strategy in Glaucoma Therapy

“…The adolescent porcine retina organ culture [17] provides excellent requirements to study CDR-induced effects on RGCs after an optic nerve cut (ONC) and is suitable to assess the effectiveness of synthetic CDR peptides as potential drug candidates in future glaucoma therapy. The immunohistochemical Brn3a staining represents an established method in our laboratory and is routinely used for the evaluation of neuroprotective effects on RGCs during stress conditions [19,48,49,50]. And indeed, quantitative analysis of RGC/mm 2 (also Brn3a + cells/mm 2 , see Figure 3a,b) revealed a significantly higher RGC survival rate in CDR-treated retinal explants (296 ± 29 RGC/mm 2 , n = 4) in contrast to untreated control explants (203 ± 45 RGC/mm 2 , n = 4, p = 0.013).…”