A Sidekick for Sight

With new research published every day on the causes of and cures for diseases of the eye, it’s easy to overlook the fact that we still lack a complete understanding of normal vision. The way the brain and the eye work together to create an image of the world around us is still, in many ways, a mystery – but one that scientists from the National Eye Institute (NEI) are working to unravel.

One group, led by Arjun Krishnaswamy, is focused on understanding a type of retinal ganglion cell (RGC) called the W3B-RGC, which acts as an object motion sensor. W3B-RGCs depolarize and fire when the movement of a small object differs from that of its background, but not when they coincide (examples of when these cells would fire include when a bird lands high in a tree, or when a wasp buzzes angrily around an office). But unlike other RGCs (that receive their visual signals directly), it turns out that the W3B-RGCs receive strong and selective input indirectly via an unusual excitatory amacrine cell type known as VG3-AC (vesicular glutamate transporter 3-amacrine cell) (1). Krishnaswamy and his colleagues theorize that the delay caused by the extra synapse allows the eye to distinguish different movements.

Both object motion sensor cells and VG3-ACs express an immunoglobulin superfamily recognition (IgSF) molecule called sidekick 2 (Sdk2). IgSF molecules are involved in the recognition, binding and adhesion processes of cells, and in this case, Sdk2 might act to bias connectivity in favour of specific pairings: VG3-ACs and W3B-RBCs. To test this, researchers at the National Eye Institute created genetically engineered mice that allowed them to control Sdk2 gene expression. They found that the protein allows object motion sensors to communicate with VG3-ACs. Transgenic mice were created that expressed a null allele of Sdk2 (Sdk2^ce/ce) – and were unable to distinguish the movements of small objects – helping to confirm the central role of Sdk2 in functional vision.

As next steps, Krishnaswamy hopes to investigate the neurological role of Sdk2 further – first by investigating its effect on mouse brain development, then by attempting to determine the role Sdk2 plays in human vision.