In January 2020 I was able to undertake a 6-week visiting scientist placement at the University of Berkeley California (UCB) in Professor Richard Kramer’s lab. The research in the Kramer lab at UCB focuses on the use of novel strategies to investigate the visual system and how this is impacted by the presence of disease, including retinal degeneration. At UCB I undertook a small research project, based on the findings of previous research (Telias et al., 2019). This research found that in mouse models of retinal degeneration there is an increase in spontaneous firing of retinal ganglion cells in the absence of light stimuli, which dampens the visual response of the remaining photoreceptive cells. There was found to be heightened retinoic acid signalling in the degenerated retinas and increasing retinoic acid signalling in healthy retinas induced the same spontaneous firing observed in degeneration. This spontaneous hyperactivity was reduced pharmacologically with the use of retinoic acid receptor inhibitors, and in turn improved the light responses of the retina.

The aim of the research that I was involved in was to investigate if a drug delivered to mice with retinal degeneration orally, disulfiram, that inhibits the activity of retinoic acid, could reduce the spontaneous firing in the degenerated retina and therefore, improve visual response. To investigate this, I used in vitro electrophysiology recordings in the eyes of diseased mice who had received either disulfiram or vehicle. These recordings allowed us to examine whether the light responsiveness was improved in the eyes of mice who had received the drugs. Preliminary findings showed increased light responses in the treated eyes compared to control. Future study is planned to determine how the drug can affect the visual level in vivo by using behavioural studies. It is hoped that the drug can be used to improve or maintain low visual levels in humans with later stage retinal degeneration, or in conjunction with other vision restoration methods such as gene therapy to optimise the visual response.

With thanks to the Professor Richard Kramer and his laboratory for affording me this opportunity and to Dr. Bristol Denlinger and Dr. Kevin Cao for their continued support.

References

Telias, M., Denlinger, B., Helft, Z., Thornton, C., Beckwith-Cohen, B. and Kramer, R. H. (2019) ‘Retinoic Acid Induces Hyperactivity, and Blocking Its Receptor Unmasks Light Responses and Augments Vision in Retinal Degeneration’, Neuron, 102(3), pp. 574-586.e5.