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Tonia S Rex, Jessica Hines-Beard; Delayed erythropoietin gene therapy preserves vision by decreasing microglia in the DBA/2J model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2423. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The current study investigates if delayed systemic gene therapy with a form of erythropoietin (EPO) that has attenuated erythropoietic activity (EPO-R76E) is effective and if EPO-R76E preserves vision in glaucoma by modulating neuroinflammation.
To result in therapeutic levels of EPO-R76E at onset of elevated intraocular pressure (IOP) DBA/2J mice were given an intramuscular injection of recombinant adeno-associated virus (rAAV) carrying either enhanced green fluorescent protein (eGFP) or EpoR76E at 5 months of age. Flash visual evoked potentials (VEP) and IOP were measured longitudinally. Axon transport of fluorescently labeled cholera toxin B to the superior colliculus was quantified. Microglial number and morphology was assessed at 8 months by immunolabeling with anti-IBA1, confocal microscopy and morphometrics analysis.<br />
Ten month old mice treated with rAAV.EpoR76E had average VEP N1 and P1 amplitudes of 34μV and 45μV, respectively as compared to 23μV and 22μV, respectively in the rAAV.eGFP controls (p<0.05). Percent axon transport was better preserved in the rAAV.EpoR76E treated mice as compared to rAAV.eGFP controls (p<0.05). The number of microglia/frame in retinas from mice treated with rAAV.EpoR76E was 11±4 as compared to 9±3 in 3 month old controls and 16±3 in rAAV.eGFP controls (p<0.001 for all groups). Soma size was 326±104mm2 in 3 month controls as compared to 713±231mm2 and 598±220mm2 in the central retina of rAAV.eGFP or rAAV.EpoR76E treated mice (p<0.001 for all groups). There was no difference in ramification between the rAAV.eGFP and rAAV.EpoR76E groups.<br />
Treatment with EPO-R76E beginning at presentation of elevated IOP preserves vision and axon transport in glaucomatous mice possibly by limiting the number of microglia present in the retina.<br />
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