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

• Published in: Cell journal (Yakhteh) 2023-05, Vol.25 (5), p.327-337
• Main Authors: Eghbali, Atiyeh, Anvarinia, Yasaman, Sanjari, Mostafa Soltan, Pakdel, Farzad, Seyedsadr, Maryam, Hosseini Mazinani, Fatemehsadat, Zare, Leila, Zarei-Kheirabadi, Masoumeh, Satarian, Leila
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Axons; Cell culture; Crushing; Cytokines; Cytotoxicity; Developmental biology; Electrodes; Erythropoietin; Fluorescence; Gene expression; Glaucoma; Glial cells; Glial fibrillary acidic protein; Gliosis; Injuries; Ischemia; Mice; Nervous system; Neuroglia; Neuronal-glial interactions; Neurons; Neuroprotection; Ophthalmology; Optic nerve; Optic neuropathy; Optomotor response; Original; Polymerase chain reaction; Research centers; Retina; Retinal ganglion cells; Reverse transcription; Stem cells; Therapeutic targets; traumatic optic neuropathy; Vision; Visual acuity; Visual evoked potentials
• ISSN: 2228-5806; 2228-5814
• DOI: 10.22074/cellj.2023.1971689.1159

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. 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 . 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, immunostaining showed while the intensity of reactive astrocytes was increased in injured retina, systemic EPO decreased it. In the treatment group, expression of was down-regulated, while was upregulated as assessed by qRT-PCR in the 60 day post-crush. 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.