Abstract
Retinal degeneration (RD) results in photoreceptor loss and irreversible visual impairments. This study sought to alleviate the photoreceptor degeneration via the adeno-associated virus (AAV)-mediated erythropoietin (EPO) therapy. AAV-2/2-mCMV-EPO vectors were constructed and delivered into the subretinal space of a RD model. The retinal morphology, optokinetic behaviour and electrophysiological function of the treated animals were analysed. The subretinal delivery of AAV-2/2 vectors induced robust EPO gene expressions in the retinas. AAV2/2-mediated EPO therapy ameliorated the photoreceptor degeneration and visual impairments of the RD animal model. Furthermore, the multi-electrodes array (MEA) was used to detect the firing activities of retinal ganglion cells. MEA recording showed that the EPO therapy could restrain the spontaneous firing response, enhance the light-induced firing response and preserve the basic configurations of visual signal pathway in RD model. Our MEA assay provided an example to evaluate the potency of pharmacological compounds on retinal plasticity. In conclusion, AAV2/2-mediated EPO therapy can ameliorate the photoreceptor degeneration and rectify the abnormities in visual signal transmission. These beneficial results suggest the AAV vector is a viable therapeutic option for retinopathies with rapidly degenerating kinetics and lay the groundwork for future development of EPO gene therapy.
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