Visual Neuroscience

CSPGs (green) are present in the retina. Blue indicates the nuclei of retinal cells including photoreceptors and RGCs. Reactive astrocytes (red) can be seen in the ganglion cell layer.

I am currently pursuing my PhD as an NIH Cambridge Scholar, working at the John van Geest Centre for Brain Repair at the University of Cambridge and at the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH). I study the cellular and molecular mechanisms of neural regeneration in the optic nerve. My long-term objective is to conduct clinical research in visual neuroscience and develop new treatments for blindness and vision loss.

Retinal ganglion cells (RGCs) carry visual information from the retina to the brain via their axons. Like other central nervous system (CNS) neurons, RGC axons show only limited regeneration after injury or damage from disease. Successful regeneration requires a stimulus to initiate axon extension, as well as a means of overcoming the growth-inhibitory environment of the adult CNS. A key aspect of this environment is the glial scar, which forms when astrocytes become reactive after injury and also includes activated microglia, macrophages, and extracellular matrix molecules such as chondroitin sulfate proteoglycans (CSPGs). The glial scar and its components inhibit growth of new axons and are thus targets for enhancing regeneration.

Even when treatments stimulate a significant population of RGC axons to regenerate beyond the site of injury, they often fail to navigate properly and very few establish successful synaptic connections to their targets in the brain. Regenerating RGC axons must retrace a complex path that takes them out of the eye, along the optic nerve, across the optic chiasm, into the optic tract, and finally to central visual targets. During development, specific guidance cues are expressed in a tightly regulated temporal and spatial manner to create a pro-migratory environment for newly projecting RGC axons. Changes in the expression of these cues in the adult optic pathway may account for the observed misguidance of regenerating RGC axons. 
 
My PhD research aims to characterise the cellular and molecular changes that occur throughout the optic pathway following acute injury. By enhancing our understanding of the extracellular environment through which regenerating RGC axons must navigate after injury, I hope to identify new targets for treatment. Our objectives are to stimulate long-distance axon regeneration throughout the optic pathway and improve the path-finding ability of regenerating axons so that they can ultimately establish active connections to their targets in the brain.

The optic pathway of a mouse has been removed and sectioned for imaging on a fluorescence microscope. Astrocyte cells are visible throughout the optic pathway.

The optic pathway of a mouse has been removed and sectioned for imaging on a fluorescence microscope. Astrocyte cells are visible throughout the optic pathway.