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.

Microvascular changes after conbercept therapy in central retinal vein occlusion analyzed by optical coherence tomography angiography

AIM: To investigate microvascular changes in eyes with central retinal vein occlusion(CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity(BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography(OCTA) automatic measurements of the vessel density in the superficial(SCP) and deep retinal capillary plexus(DCP), the foveal avascular zone(FAZ) area, the FAZ perimeter(PERIM), the vessel density within a 300-μm wide ring surrounding the FAZ(FD-300), the acircularity index(AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age-and sexmatched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were allsignificantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher(all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65(P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness.CONCLUSION: OCTA enables the non-invasive, layerspecific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.

Prevalence and characteristics of peripheral myopic retinopathy in Guangzhou office workers

AIM: To determine the prevalence and characteristics of peripheral myopic retinopathy among a sample of Guangzhou office workers. METHODS: A cross-sectional study of Guangzhou Chinese office works in different departments and units of the Guangzhou Power Supply Bureau, China, in 2016. Myopic retinopathy was recorded and analyzed with a scanning laser ophthalmoscope and by slit-lamp microscopy combined with a three-mirror contact lens. RESULTS: In total, 1910 eyes of 955 subjects(508 females and 447 males) aged 21-59 y were included; 69.6% of these eyes were myopic. The myopia group had a younger age and worse uncorrected visual acuity(UCVA) and bestcorrected visual acuity(BCVA) when compared with hyperopia and emmetropia groups(P<0.001). The axial length(AL) was significantly longer, the spherical equivalent(SE) was more serious, and the optic nerve crescent was significantly larger in subjects with myopia than with hyperopia and emmetropia. Subjects with myopia, and especially high myopia, had the highest frequency of myopic retinal 18 changes(49.4%, P<0.001) [white-without-pressure(43.8%, P<0.001), lattice degeneration(4.5%, P=0.044)] among the three groups. Logistic regression confirmed that any myopia(OR: 3.41, P<0.001) [mild myopia(OR: 1.93, P=0.001), moderate myopia(OR:3.64, P<0.001), and high myopia(OR:10.58, P<0.001)], a greater AL(OR: 1.55, P<0.001) and a much higher SE(OR: 0.77, P<0.001) increased the risk for peripheral retinal changes.CONCLUSION: Myopia-related retinal changes are positively associated with greater AL, higher SE, and myopia.