Adeno-associated virus (AAV)-mediated neuroprotective effects on the degenerative retina: the therapeutic potential of erythropoietin.

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.

Intravitreal Delivery of Melatonin Is Protective Against the Photoreceptor Loss in Mice: A Potential Therapeutic Strategy for Degenerative Retinopathy.

Melatonin is a circadian hormone with potent cytoprotective effects. Retinitis pigmentosa (RP) comprises a heterogeneous group of inherent retinopathies that characterized by the photoreceptor death in bilateral eyes. The N-methyl-N-nitrosourea (MNU) administered mouse is a type of chemically induced RP model with rapid progressive rate. We intend to study the melatonin mediated effects on the MNU administered mice. Melatonin was delivered into the vitreous body of the MNU administered mice. Subsequently, the melatonin treated mice were subjected to histological analysis, optokinetic behavior tests, spectral-domain optical coherence tomography (SD-OCT), and electroretinogram (ERG) examination. Multi-electrodes array (MEA) was used to analyze the status of visual signal transmission within retinal circuits. Biochemical analysis was performed to quantify the expression levels of antioxidative enzymes, oxidative stress markers, and apoptotic factors in the retinas. The intravitreal injection of melatonin ameliorated effectively the MNU induced photoreceptor degeneration. Melatonin therapy mitigated the spontaneous firing response, and preserved the basic configurations of visual signal pathway in MNU administered mice. MEA is effective to evaluate the pharmacological effects on retina. Of note, the cone photoreceptors in degenerative retinas were rescued efficiently by melatonin therapy. Melatonin afforded these protective effects by modulating the apoptotic cascades and alleviating the oxidative stress. These findings suggest that melatonin could act as an alternative treatment for degenerative retinopathy. Melatonin might be used in combination with other therapeutic approaches to alleviate the photoreceptor loss and preserve the visual function of RP patients.