Eye Plasticity

Is how the eye remodels itself during foetal development providing a model for changes in our plastic brain?

KEY POINTS

• Early development in the eye provides a model for neuronal plasticity.
• Elucidating the mechanisms of normal neuronal development will help understand disease processes.
• Innate immunity mechanisms through the HLA Class I molecules seem to have shared roles in both fighting the foreign and neuronal recognition processes. 

Elucidation of remodelling processes as complex human vision pathways develop in the foetus may provide clues to the mechanisms of neural plasticity that drive nervous system adaptation.

• Clues to the Normal and Disease

The processes of plasticity in neuronal circuits and cells are not only significant for normal functioning but also they play a role in complex and diverse brain and nervous system disorders. An increased understanding of these processes may help in the future treatment of disease and also, for example, aid the recovery from brain damage by conditions such as stroke.

To understand disease it is important first to understand what is normal. Our understanding of how the brain works and how it remodels itself is key to our understanding of brain complexity and normal- and disease-related plasticity.

• Throwing Light on Vision

The development of our highly evolved vision system provides an ideal model for how neural circuits and cells connect and how they remodel.

We start off in the womb with a primitive non-light dependent system. Then biochemical processes trigger activity that leads to the development of our complex visual sensory pathways. In early development, there is neuronal activity with spontaneous firing leading to the remodelling of the circuits involved in vision. It is this activity that leads to the development of the more complex adult wiring.

• Role for the Immune

Analysis of the molecular mechanisms driving this early sophistication has surprisingly shown the involvement of similar molecules to those with a central role in innate immunity – the MHC class 1 molecules – the distinguisher of what is self and non-self. The MHC1 molecules in neurons seem to bind to a similar receptor molecule to the T-cell receptor called PirB. This interaction has been found to play a role in the switch from the more primitive in utero visual system to our more complex final adult wiring.

The optic tract leads from the retina and ends in the lateral geniculate nucleus (LGN), which is a sensory relay nucleus in the thalamus brain region. Maturing of the optic circuits occurs, so they up the normal pattern and organisation.

• Foetal Development

In the foetus, there are initially no layers in the LGN. The ganglion cell inputs from the two eyes are intermixed and then gradually sort out to form the layers. In adult wiring, there is ocular dominance manifest in the LGN, and it is highly ordered such that ganglion cells from opposite eyes form connections within separate but adjacent interdigitated, eye-specific layers.

Blocking the neuronal activity in utero or preventing vision after birth disrupts rewiring plasticity of optic circuits and the immature pattern persists.

The rewiring involves elimination of inappropriate ganglions through  a process of weakening and regression and those that are made in the appropriate area are strengthened and stabilised.

• Therapeutic Clues

Elucidation of the mechanisms involved in synaptic plasticity may offer a range of therapeutic options for behavioural disorders such schizophrenia and autism.

Cell and circuit changes accompany these disorders and there may be commonality between the processes in the development of wiring in the eye.

Even if we know all of the genes and the mutations or deletions involved in development disorders, such as schizophrenia or autism, then we will not know everything about these diseases until we understand the detailed circuit and cellular changes that occur in the disease state.

• Conclusion

The way the immune and nervous system interact through the function of the MHC1 genes may partially explain some of the aetiology of these developmental disorders.

It seems as it the immune and nervous system share a common molecular language. This is important because when the immune system is in the brain it needs to communicate to have an effect on the neurons. Immune cells interact directly with neurons by interrogating their MHC1 proteins. The release of cytokines in the microenvironment of cells within the nervous system and brain may have profound effects in health and disease.

Conor Caffrey is a medical and science writer.

After a presentation by Carla Schatz at the Wiring the Brain Conference held in Powerscourt, County Wicklow.