Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis

Sättler, Muriel B.; Merkler, Doron; Maier, Katharina; Stadelmann, Christine; Ehrenreich, Hannelore; Bähr, Mathias; Diem, Ricarda

doi:10.1038/sj.cdd.4401504

Cited by 164 publications

(101 citation statements)

References 56 publications

(72 reference statements)

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“…Several distinguished investigations addressed the properties of the EPO to mediate protection against retinal damage through anti-apoptotic, 29,30 anti-oxidant, 22 and antiinflammatory 26,31 actions in hypoxia-, light-, and geneticinduced models. 5,8,12,15 Furthermore, Chung et al 20 reported on his finding for the expression of EPO and Figure 2 The role of erythropoietin in eye development via anti-apoptotic action.…”

Section: The Role Of Epo In the Eyementioning

confidence: 99%

“…The role of EPO in neural protection by anti-apoptosis makes it an ideal treatment in ocular disorders such as AMD, 67 retinitis pigmentosa, 10 glaucoma, 68,69 optic neuritis, 30 and retinal detachment. 32 Besides that, it is able to restore proteins at the tight junction level and protect BRB.…”

Section: Application Of Epo Therapy For Ocular Disordersmentioning

confidence: 99%

“…32 Besides that, it is able to restore proteins at the tight junction level and protect BRB. This added benefit makes it a favorable treatment in early DR, 35,70 optic neuritis, 30,59 and retinopathy of prematurity. 9 However, EPO therapy is a double-edged sword in the treatment of eye disease.…”

Section: Application Of Epo Therapy For Ocular Disordersmentioning

confidence: 99%

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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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Section: The Role Of Epo In the Eyementioning

confidence: 99%

Section: Application Of Epo Therapy For Ocular Disordersmentioning

confidence: 99%

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Revisiting the role of erythropoietin for treatment of ocular disorders

Ding

Leow

Munisvaradass

et al. 2016

Eye

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“…Besides its haematopoietic effect, EPO has revealed neuroprotective effects on the central nervous system [6,7,8,9]. Recent studies involving EPO in glaucoma have yielded very promising results [10,11,12].…”

Section: Introductionmentioning

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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“…Apart from this ''actively-induced EAE,'' it can also be induced by passive transfer of T cells from actively immunized animals (''adoptive transfer EAE''), which highlights the crucial role of T cells in this animal model. EPO has been tested in actively-induced EAE and various studies have shown that the administration of EPO delays disease onset and attenuates disease severity [16,[50][51][52][53][54]. This clinical improvement is associated with a decrease in levels of TNF and IL-6 [16].…”

Section: Epo In Experimental Autoimmune Encephalomyelitismentioning

confidence: 99%