Melanopsin Retinal Ganglion Cells in Patiens with Leber Hereditary Optic Neuropathy: an fMRI Study of Brain Activations under Monochromatic Light Stimulations

The current PhD thesis focused on a project that investigated brain responses to monochromatic light stimulation, as assessed by functional magnetic resonance imaging (fMRI), in a population of patients with Leber's hereditary optic neuropathy (LHON). In particular, the aim was to explore a possible role of melanopsin retinal ganglion cells (mRGCs) in visual processes and to assess their role in modulating brain responses during cognitive tasks, as in LHON patients it has been shown that mRGCs are relatively spared despite the general RGCs degeneration. Eleven LHON patients, and eleven matched healthy controls, underwent an fMRI protocol (1.5T MR scanner) that included purely visual stimulation and the combination n of a sustained attention task and light stimulation, both with blue (480nm) and red (620nm) light exposures of equivalent photon flux (5x1013ph cm?2s?1). Overall, lower activations of primary visual cortex in response to purely visual stimuli were observed in LHON compared to healthy subjects, and this is in line with the disease. When considering sustained brain response to monochromatic light stimuli (of 10 and 50s of duration), a higher cortical activity was found in LHON in response to blue rather than to red light, and only when considering blue light no differences between the two groups were observed. Moreover, a prominent modulation of brain responses to a cognitive sustained attention task was found under blue light exposure compared to the red one, both in cortical and subcortical areas. These results provide support to the relatively new hypothesis of melanopsin role in visual processes, and they give a confirmation of the maintained functionality of mRGCs in modulating brain activity during cognitive engagement for LHON patients, as it was previously shown for healthy subjects.