Evidence That Erythropoietin Modulates Neuroinflammation through Differential Action on Neurons, Astrocytes, and Microglia

Bond, Wesley S.; Rex, Tonia S.

doi:10.3389/fimmu.2014.00523

Cited by 84 publications

(87 citation statements)

References 107 publications

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“…Several investigations have addressed EPO properties to mediate protection against retinal damage through different pathways, including increasing resistance to inflammation, oxide-induced damage, ischemia, degeneration, and permeability [13,27]. Concerning RGCs, which are especially affected in glaucoma disease, EPO provides protection against apoptosis by activation of STAT5, MAPK/ERK, and PI3K/Akt.…”

Section: Discussionmentioning

confidence: 99%

Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals

et al. 2018

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Keywords Erythropoietin · Glaucoma · Subconjunctival route · Retinal ganglion cells · RatAbstract Purpose: The present study aimed to assess functional and structural benefits of erythropoietin (EPO) when administered subconjunctivally in the retina of glaucomatous rats using electroretinography (ERG) and retinal thickness (RT) measurements. Methods: Glaucoma was experimentally induced in 26 Wistar Hannover albino rats. Animals were divided into 2 groups of 13 animals each: a treated group receiving a unique subconjunctival injection of 1,000 IU of EPO and a control group receiving a saline solution. In each group, 7 animals were used for retinal function evaluation (ERG) and 6 animals were used for retinal structural evaluation (histology). RT was measured, dorsally and ventrally, at 500 μm (RT1) and at 1,500 μm (RT2) from the optic nerve. Results: Retinal function evaluation: for both scotopic and photopic conditions, ERG wave amplitudes increased in the treated group. This increase was statistically significant (p < 0.05) in photopic conditions. Structural evaluation: for both locations RT1 and RT2, the retinas were significantly (p < 0.05) thicker in the treated group. Conclusion: Sub- What Is It about?Glaucoma is the leading cause of irreversible blindness worldwide. Erythropoietin (EPO) has revealed neuroprotective properties on the retina, preserving visual function in several glaucoma models. The present study assesses functional and structural benefits of EPO when administered subconjunctivally in the retina of glaucomatous albino rats using electroretinography and retinal thickness measurements. Subconjunctival EPO administration, a mini-invasive and safe periocular route, showed beneficial effects both on retinal structure and on retinal function. This neuroprotective effect should be applied in other animal species, and more studies should be performed to assess EPO kinetics when administered via a subconjunctival route in glaucoma conditions. conjunctival EPO administration showed beneficial effects both on retinal structure and on retinal function in induced glaucoma in albino rats. This neuroprotective effect should be applied in other animal species.

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Section: Discussionmentioning

confidence: 99%

Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals

et al. 2018

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“…EPO acts in the retina in different ways, including increasing resistance to inflammation, oxide-induced damage, ischaemia, degeneration and permeability [14,20,21]. Concerning RGCs, especially affected in glaucoma, EPO provides protection against apoptosis by activation of STAT5, MAPK/ERK and PI3K/Akt.…”

Section: Discussionmentioning

confidence: 99%

Ocular Erythropoietin Penetration after Subconjunctival Administration in Glaucomatous Rats

Resende

Bráz

Delgado³

2016

Ophthalmic Res

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Purpose: The present study aimed to determine whether the subconjunctival administration of recombinant human erythropoietin (rHuEPO) reached the retina in glaucoma conditions. After subconjunctival rHuEPO administration, in a rat glaucoma model, erythropoietin (EPO) distribution in the rat's retina was studied by immunohistochemistry. Methods: Female Wistar Hannover albino rats (n = 15) were divided into 2 groups, control (n = 3) and treated (n = 12). The animals' unilateral glaucoma was induced by coagulation of episcleral veins, under general anaesthesia. After vein coagulation, 1,000 IU of rHuEPO were administered by the subconjunctival route to the treated group (n = 12). The control group (n = 3) received only a subconjunctival saline injection. The contralateral eye of each animal remained untouched. Treated group animals were euthanized at different time points, i.e. days 1, 3, 7 and 14. Bilateral enucleation was performed, and EPO distribution in the rat's retina was assessed by immunohistochemistry. Results: Glaucoma was confirmed by results of repeated intraocular pressure measurements over the experimental period. In the test group, EPO was identified in different neuroretinal cells, showing a stronger immunostaining signal during the first 2 time points in the retinal ganglion cell (RGC) layer. EPO protein was still present on day 14 after the subconjunctival injection. EPO was not detected in any of the control eyes or in any contralateral eye of the treated group. Conclusion: When administered subconjunctivally to glaucomatous eyes, rHuEPO reached the RGC layer and was still present at least 14 days after administration. The subconjunctival route was shown to be a promising alternative for ocular EPO delivery in glaucomatous conditions in a rat animal model.

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“…The Wnt signaling pathway has an important role in the developmental processes of the eye field, lens, and retina. [16][17][18] As presented in Figure 3, binding of EPO to heterodimeric EPOR/βcR complex, leads to binding of Wnt to the Frizzled transmembrane receptors and subsequent inhibition of the β-catenin phosphorylation by glycogen synthase kinase (GSK)-3β. Activated β-catenin then escapes from proteasomal destruction , the outer nuclear layer (ONL), the outer plexiform layer (OPL), the inner nuclear layer (INL), the inner plexiform layer (IPL), and the ganglion cell layer.…”

Section: The Role Of Epo In the Eyementioning

confidence: 99%

Revisiting the role of erythropoietin for treatment of ocular disorders

Ding

Leow

Munisvaradass

et al. 2016

Eye

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Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.

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Evidence That Erythropoietin Modulates Neuroinflammation through Differential Action on Neurons, Astrocytes, and Microglia

Cited by 84 publications

References 107 publications

Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals

Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals

Ocular Erythropoietin Penetration after Subconjunctival Administration in Glaucomatous Rats

Revisiting the role of erythropoietin for treatment of ocular disorders

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