A zebrafish retina showing retinal ganglion cells (RGCs; in green) connecting to other neural cells (in magenta) in the inner synaptic layer (IPL) between them. Image credit: Ahmed et al. (CC BY 4.0).
The back of the eye is lined with an intricate tissue known as the retina, which consists of carefully stacked neurons connecting to each other in well-defined ‘synaptic’ layers. Near the surface, photoreceptors cells detect changes in light levels, before passing this information through the inner plexiform layer to retinal ganglion cells (or RGCs) below. These neurons will then relay the visual signals to the brain. Despite the importance of this inner retinal circuit, little is known about how it is created as an organism develops.
As a response, Ahmed et al. sought to identify which genes are essential to establish the inner retinal circuit, and how their absence affects retinal structure. To do this, they introduced random errors in the genetic code of zebrafish and visualised the resulting retinal circuits in these fast-growing, translucent fish. Initial screening studies found fish with mutations in a gene encoding a protein called Strip1 had irregular layering of the inner retina.
Further imaging experiments to pinpoint the individual neurons affected showed that in zebrafish without Strip1, RGCs died in the first few days of development. Consequently, other neurons moved into the RGC layer to replace the lost cells, leading to layering defects. Ahmed et al. concluded that Strip1 promotes RGC survival and thereby coordinates proper positioning of neurons in the inner retina.
In summary, these findings help to understand how the inner retina is wired; they could also shed light on the way other layered structures are established in the nervous system. Moreover, this study paves the way for future research investigating Strip1 as a potential therapeutic target to slow down the death of RGCs in conditions such as glaucoma.
