Overexpressing NeuroD1 reprograms Müller cells into various types of retinal neurons

The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that in adult mice, NeuroD1 can reprogram Müller cells, the principal glial cell type in the retina, to become retinal neurons. Most strikingly, ectopic expression of NeuroD1 using two different viral vectors converted Müller cells into different cell types. Specifically, AAV7 m8 GFAP681::GFP-ND1 converted Müller cells into inner retinal neurons, including amacrine cells and ganglion cells. In contrast, AAV9 GFAP104::ND1-GFP converted Müller cells into outer retinal neurons such as photoreceptors and horizontal cells, with higher conversion efficiency. Furthermore, we demonstrate that Müller cell conversion induced by AAV9 GFAP104::ND1-GFP displayed clear dose-and time-dependence. These results indicate that Müller cells in adult mice are highly plastic and can be reprogrammed into various subtypes of retinal neurons.

Is there a relationship between dopamine and rhegmatogenous retinal detachment?

Dopamine and its receptors have been widely studied in the neurological conditions and in the retina. In this study, we evaluated the possible role of dopamine in rhegmatogenous retinal detachment(RRD) by comparing the amount of 3,4-dihydroxyphenylacetic acid(DOPAC), a surrogate index of retinal dopamin levels, in the vitreous sample of patients affected by RRD with those affected by macular pucker and vitre ous hemorrhage. Our results showed that significantly higher levels of DOPAC were found in the vitreou sample of patients affected by RRD compared with those affected by vitreous hemorrhage and macula pucker(P = 0.002). Specifically, no trace of the substance was found in vitreous hemorrhage and macula pucker samples. A slightly significant positive correlation was found among DOPAC and post-operativ best corrected visual acuity(r = 0.470, P = 0.049). No correlation was found between DOPAC and the day elapsed between diagnosis and surgery(P = 0.317). For the first time our findings suggest that DOPAC i released in RRD, but not in other retinal diseases such as vitreous hemorrhage and macular pucker. More over, we showed a correlation between visual acuity outcome and the amount of DOPAC in the vitreous This might have a potential, although still unknown, implication in the pathogenesis of the disease and/o in the associated photoreceptors loss. This study was approved by the Ethics Committee of Rome Tor Ver gata University Hospital(R.S.92.10) on September 24, 2010.