From bench to bicycle: new insights into monocular deprivation mechanisms of homeostatic plasticity in mice and recovery from amblyopia in human patients

The first aim of the present Thesis was to characterize a new model for short-term monocular deprivation effects in mice, investigating the underlying mechanisms. In adult wild-type mice (~2-4 months). Awake mice underwent three sessions of electrophysiological recordings over two consecutive days. On Day 1, recordings were first conducted before deprivation (Pre), then after 2 hours of deprivation of either the ipsilateral or contralateral eye relative to the recording site (Post), and again after 2 hours of binocular vision (After 2h). On Day 2, I performed, as control, three consecutive recordings, spaced 2 hours apart, without any eye deprivation. I found that 2 hours of monocular deprivation transiently shifted the OD of mice in favor of the deprived eye, irrespective of whether it was contralateral or ipsilateral eye to have been deprived. Then, I explored whether short-term monocular deprivation could induce homeostatic plasticity phenomena in juvenile mice (P28), in which plasticity has classically been attributed to competition between the two eyes. Ipsilateral eye deprivation resulted in a pronounced and transient OD shift toward the deprived eye. This effect was more marked with respect to that observed in adult mice. Finally, the reduction of PV interneurons activity amplified the effects of deprivation observed in adult mice, resulting in a marked OD shift toward the deprived eye. Thus, the results obtained in mice support previously reported findings in humans and provide a valuable platform for further research focused on the mechanisms underlying short-term monocular deprivation effects. The second aim of my Thesis was to assess the translational potential of this paradigm for amblyopia treatment in young human adults. To this purpose, I employed a protocol of occlusion of the amblyopic eye with a translucent patch for two hours, during which patients engaged in moderate physical exercise on a stationary bicycle. A telemedicine-based treatment program was then developed, allowing patients to perform training at home with remote supervision via video call. Throughout the treatment, a progressive improvement in visual acuity was observed. The improvement turned out to be longlasting, as it persisted six months after the end of the treatment. The results obtained in amblyopic subjects open the way to further clinical applications of this non-invasive intervention based on short-term eye patching of the amblyopic eye combined with the plasticising effect of voluntary physical exercise.