Microscopy image of an injured chick retina showing neurofilament (green) in the axons of neurons and the cell bodies of progenitor cells, a transcription factor expressed by retinal progenitors and Müller glia (Sox9; magenta), and a marker of proliferating cells (phosphor-histone H3: red). Image credit: Taylor et al. (CC BY 4.0)
The retina is a layered structure of the central nervous system located at the back of our eyes that contains neuronal cells. Retinal neurons convert visible light into nerve signals, which travel from our eyes to our brain along the optic nerve, allowing us to see. Healthy retinas are, therefore, critical for vision.
Unfortunately, many factors can damage our retinas. These range from acute eye injuries to eye diseases like diabetic retinopathy and glaucoma; if too many neurons are damaged, it can lead to blindness. In some animals, damaged retinas can repair themselves, or ‘regenerate’. This ability varies depending on the species: in fish, retinal regeneration is highly efficient, but it is reduced in birds and entirely absent in mammals – including humans.
In animals that can regenerate their retinas, the resident support cells of the retina (called Müller glia) respond to retinal injury by dividing to form progenitor cells. These progenitor cells can further reprogram into new neurons to replace damaged tissue and restore sight. The efficiency of this regeneration process depends on how many cells proliferate and the ability of these progenitors to become neurons. In birds, for example, many progenitor cells are formed, but only a fraction turn into neurons.
In the Müller glia of birds – specifically, in chicks – the activity of the genes for a set of biological signals (collectively termed the S1P signalling pathway, or S1P) changes after retinal injury. More generally, S1P is also known to be associated with tissue damage and inflammation. Taylor et al. therefore wanted to determine if S1P played a role in chick retinal regeneration, particularly in the development of Müller glia into ‘successful’ progenitor cells capable of replacing damaged neurons.
Taylor et al. employed a combination of microscopy and genetic techniques to track the production of various cell types and measure S1P gene activity under different conditions. When chick retinas were treated with drugs known to suppress S1P activity, the production of progenitor cells increased. Importantly, these new progenitor cells were also more likely to develop into new neurons. In contrast, drugs that turned on S1P activity resulted in fewer progenitor cells being formed. These findings suggest that S1P signalling activity suppresses retinal regeneration.
This study adds to our understanding of how inflammatory signals control the retina’s ability to repair itself after damage. However, more research is needed to determine the role of S1P in mammalian retinas. Ultimately, Taylor et al. hope that the knowledge gained will produce treatments to recover vision for people with retinal disease.
