Polydopamine nanoparticles attenuate retina ganglion cell degeneration and restore visual function after optic nerve injury

Background Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs. Results The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function. Conclusions The PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases. Graphical Abstract

Polydopamine Nanoparticles Attenuate Retina Ganglion Cell Degeneration and Restore Visual Function After Optic Nerve Injury

Background: Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs. Results: The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function. Conclusions: the PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases.

Development of the retina and its relation with myopic shift varies from childhood to adolescence

AimsTo elucidate the influence of age and myopic shift on retinal development.MethodsThis 1-year longitudinal study included 769 participants aged 6–17 years. Cycloplegic refraction, axial length and swept-source optical coherence tomography were examined at baseline and follow-up. The thickness changes in the retina, ganglion cell complex (GCC) and outer retinal layers (ORL) in the macular region were calculated, and their relation with age and myopic shift was analysed with multiple linear regression analysis.ResultsThe thickness of the central foveal retinal layers was increased in children (<10 years) but unchanged or decreased in adolescents (>13 years). The thickness changes in the retina, GCC and ORL decreased with age (r=−0.24,–0.23, −0.15, respectively, all p<0.01). Multiple regression analysis showed that the changes in central foveal retinal thickness (RT) and GCC thickness were independently associated with age and baseline spherical equivalent (SE), while the changes in ORL thickness were associated with age and SE changes. In children 8–9 years, a greater increase was observed in central foveal ORL thickness in those with no myopic shift (p<0.01). The thickness of the most parafoveal and perifoveal retinal layers was less increased or more decreased in children <9 years with myopic shift (p<0.05).ConclusionsRetinal development and its relation with myopic shift varies from childhood to adolescence. Myopia-related retinal thinning may result from less increase in the RT in childhood rather than a decrease in RT in adolescents. Children under 9 years old could be at a critical age for future myopia-related retinal thinning.

Time-Multiplexed Spiking Convolutional Neural Network Based on VCSELs for Unsupervised Image Classification

In this work, we present numerical results concerning a multilayer “deep” photonic spiking convolutional neural network, arranged so as to tackle a 2D image classification task. The spiking neurons used are typical two-section quantum-well vertical-cavity surface-emitting lasers that exhibit isomorphic behavior to biological neurons, such as integrate-and-fire excitability and timing encoding. The isomorphism of the proposed scheme to biological networks is extended by replicating the retina ganglion cell for contrast detection in the photonic domain and by utilizing unsupervised spike dependent plasticity as the main training technique. Finally, in this work we also investigate the possibility of exploiting the fast carrier dynamics of lasers so as to time-multiplex spatial information and reduce the number of physical neurons used in the convolutional layers by orders of magnitude. This last feature unlocks new possibilities, where neuron count and processing speed can be interchanged so as to meet the constraints of different applications.

In vivo and in vitro knockout system labelled using fluorescent protein via microhomology-mediated end joining

Gene knockout is important for understanding gene function and genetic disorders. The CRISPR/Cas9 system has great potential to achieve this purpose. However, we cannot distinguish visually whether a gene is knocked out and in how many cells it is knocked out among a population of cells. Here, we developed a new system that enables the labelling of knockout cells with fluorescent protein through microhomology-mediated end joining–based knock-in. Using a combination with recombinant adeno-associated virus, we delivered our system into the retina, where the expression of Staphylococcus aureus Cas9 was driven by a retina ganglion cell (RGC)–specific promoter, and knocked out carnitine acetyltransferase (CAT). We evaluated RGCs and revealed that CAT is required for RGC survival. Furthermore, we applied our system to Keap1 and confirmed that Keap1 is not expressed in fluorescently labelled cells. Our system provides a promising framework for cell type–specific genome editing and fluorescent labelling of gene knockout based on knock-in.