Lorenceau, J. | Search bioRxiv

bioRxiv2023

Method to quickly map multifocal Pupillary Response Fields (mPRF) using Frequency Tagging

We present a method for mapping multifocal Pupillary Response Fields in a short amount of time, using a visual stimulus covering 40{degrees} of visual angle, divided in 9 contiguous sectors, simultaneously modulated in luminance at specific, incommensurate, temporal frequencies. We tested this multiple Pupillary Frequency Tagging (mPFT) approach with young healthy participants (N=36), and show that the spectral power of the sustained pupillary response elicited by 45 seconds of fixation of this multipartite stimulus reflects the relative contribution of each sector/frequency to the overall pupillary response. We further analyze the phase lag for each temporal frequency as well as several global features related to pupil state. Test retest performed on a subset of participants indicates good repeatability. We also investigate the existence of structural (RNFL)/functional (mPFT) relationships. We then summarize results of clinical studies conducted with mPFT on patients with neuropathies and retinopathies and show that the features derived from pupillary signal analyzes, the distribution of spectral power in particular, allows sorting patients from healthy participants with excellent sensitivity and specificity. This method thus appears a convenient, objective and fast tool for assessing the integrity of retino-pupillary circuits, as well as idiosyncrasies, that permits to objectively detect or follow-up retinopathies or neuropathies in a short amount of time.

neuroscience↗

bioRxiv2022

Failed remyelination of the non-human primate optic nerve leads to axon degeneration, retinal damages and visual dysfunction.

White matter disorders of the CNS such as MS, lead to failure of nerve conduction and long-lasting neurological disabilities affecting a variety of sensory and motor systems including vision. While most disease-modifying therapies target the immune and inflammatory response, the promotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery. Most of these strategies are developed in short-lived rodent models of demyelination, which spontaneously repair and do not reflect the size, organization, and biology of the human CNS. Thus, well-defined non-human primate models are required to efficiently advance therapeutic approaches for patients. Here, we followed the consequence of long-term toxin-induced demyelination of the macaque optic nerve on remyelination and axon preservation, as well as its impact on visual functions. Findings from oculo-motor behavior, ophthalmic examination, electrophysiology, and retinal imaging indicate visual impairment involving the optic nerve and retina. These visual dysfunctions fully correlated at the anatomical level, with sustained optic nerve demyelination, axonal degeneration, and alterations of the inner retinal layers. This non-human primate model of chronic optic nerve demyelination associated with axonal degeneration and visual dysfunction, recapitulates several key features of MS lesions and should be instrumental in providing the missing link to translate emerging repair pro-myelinating/neuroprotective therapies to the clinic for myelin disorders such as MS. Significance StatementPromotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery in white matter diseases such as MS. To date most of these strategies are developed in short-lived rodent models of demyelination, which spontaneously repair. Well-defined non-human primate models closer to man would allow to efficiently advance therapeutic approaches. Here we present a non-human primate model of optic nerve demyelination that recapitulates several features of MS lesions. The model leads to failed remyelination, associated with progressive axonal degeneration and visual dysfunction, thus providing the missing link to translate emerging pre-clinical therapies to the clinic for myelin disorders such as MS.

neuroscience↗