Inner retina and melanopsin retinal ganglion cells in Parkinson's disease
Authors: La Morgia Chiara , Romagnoli Martina , Carbonelli Michele , Amore Giulia , Carelli Valerio 
Published: December 2022

AbstractParkinson's disease (PD) is a neurogenerative disorder characterized by sleep and circadian dysfunction.Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive retinal ganglion cells mainly contributing to circadian photoentrainment by projecting to the suprachiasmatic nucleus of the hypothalamus. They also regulate pupillary light response projecting to the olivary pretectal nucleus.In PD there is evidence of inner retinal pathology as documented by OCT studies showing optic nerve thinning (Zhou et al., 2021). Interestingly, retinal nerve fibre layer thinning is more evident in the temporal sector of the optic nerve and more pronounced in the eye contralateral to the most affected body side (La Morgia et al., 2013). Moreover, α‐synuclein deposition has been reported in the inner retina of PD patients (Bodis‐Wollner et al., 2014).Furthermore, there is evidence of mRGC loss but also of morphological abnormalities (reduced dendritic arborization) in PD retinas which can contribute to circadian and sleep dysfunction reported in PD patients (Ortuño‐Lizarán et al., 2018). Interestingly, also the melanopsin‐mediated pupil function (i.e. post‐illumination pupil response‐PIPR) is abnormal in PD patients and is correlated to poor sleep function again supporting a dysfunction of mRGCs in PD (Joyce et al., 2018; Feigl et al., 2020). The presence of mRGC‐mediated pupil dysfunction has been recently described also in isolated REM behaviour disorder (iRBD), the prodromal stage of PD (La Morgia et al.,2022) and PIPR has been recently proposed as a biomarker of cognitive dysfunction in iRBD (Steiner et al., 2022).References1. La Morgia C, Barboni P, Rizzo G, Carbonelli M, Savini G, Scaglione C, Capellari S, Bonazza S, Giannoccaro MP, Calandra‐Buonaura G, Liguori R, Cortelli P, Martinelli P, Baruzzi A, Carelli V. Loss of temporal retinal nerve fibres in Parkinson disease: a mitochondrial pattern? Eur J Neurol. 2013 Jan;20(1):198–201.2. Bodis‐Wollner I, Kozlowski PB, Glazman S, Miri S. α‐synuclein in the inner retina in parkinson disease. Ann Neurol. 2014 Jun;75(6):964–6.3. Zhou WC, Tao JX, Li J. Optical coherence tomography measurements as potential imaging biomarkers for Parkinson's disease: A systematic review and meta‐analysis. Eur J Neurol. 2021 Mar;28(3):763–774.4. Ortuño‐Lizarán I, Esquiva G, Beach TG, Serrano GE, Adler CH, Lax P, Cuenca N. Degeneration of human photosensitive retinal ganglion cells may explain sleep and circadian rhythms disorders in Parkinson's disease. Acta Neuropathol Commun. 2018 Sep 10;6(1):90.5. Joyce DS, Feigl B, Kerr G, Roeder L, Zele AJ. Melanopsin‐mediated pupil function is impaired in Parkinson's disease. Sci Rep. 2018 May 17;8(1):7796.6. Feigl B, Dumpala S, Kerr GK, Zele AJ. Melanopsin Cell Dysfunction is Involved in Sleep Disruption in Parkinson's Disease. J Parkinsons Dis. 2020;10(4):1467–1476.7. La Morgia C, Romagnoli M, Pizza F, Biscarini F, Filardi M, Donadio V, Carbonelli M, Amore G, Park JC, Tinazzi M, Carelli V, Liguori R, Plazzi G, Antelmi E. Chromatic Pupillometry in Isolated Rapid Eye Movement Sleep Behaviour Disorder. Mov Disord. 2022 Jan;37(1):205–210.8. Steiner O, de Zeeuw J, Stotz S, Bes F, Kunz D. Post‐Illumination Pupil Response as a Biomarker for Cognition in α‐Synucleinopathies. J Parkinsons Dis. 2022;12(2):593–598.