Erythropoietin Protects against Retinal Damage in A Rat Model of Optic Neuropathy via Glial Suppression

Document Type : Original Article


1 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

2 Neuro-Ophthalmology Unit, Rassoul Akram Hospital, Iran University of Medical Science, Tehran, Iran

3 Ophthalmic Research Center, Tehran University of Medical Sciences, Tehran, Iran


Objective: Traumatic optic neuropathy (TON) causes partial or complete blindness because death of irreplaceable
retinal ganglion cells (RGCs). Neuroprotective functions of erythropoietin (EPO) in the nervous system have been
considered by many studies investigating effectiveness of this cytokine in various retinal disease models. It has been
found that changes in retinal neurons under conditions of glial cells are effective in vision loss, therefore, the present
study hypothesized that EPO neuroprotective effect could be mediated through glial cells in TON model.
Materials and Methods: In this experiment study, 72 rats were assessed in the following groups: intact and optic nerve
crush which received either the 4000 IU EPO or saline. Visual evoked potential and optomotor response and RGC
number were assessed and regenerated axons evaluated by anterograde test. Cytokines gene expression changes
were compared by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Density of astrocytes cells,
assessed by fluorescence intensity, in addition, possible cytotoxic effect of EPO was measured on mouse astrocyte
culture in vitro.
Results: In vitro data showed that EPO was not toxic for mouse astrocytes. Intravenous injection of EPO improved
vision, in terms of visual behavioral tests. RGCs protection was more than two times in EPO, compared to the vehicle
group. More regenerated axons were determined by anterograde tracing in the EPO group compared to the vehicle.
Moreover, GFAP immunostaining showed while the intensity of reactive astrocytes was increased in injured retina,
systemic EPO decreased it. In the treatment group, expression of GFAP was down-regulated, while CNTF was upregulated
as assessed by qRT-PCR in the 60th day post-crush.
Conclusion: Our study showed that systemic administration of EPO can protect degenerating RGCs. Indeed,
exogenous EPO exerted neuroprotective and neurotrophic functions by reducing reactive astrocytic gliosis. Therefore,
reduction of gliosis by EPO may be considered as therapeutic targets for TON.


Main Subjects

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