Mirella Telles Salgueiro Barboni1,2, Clarissa Bueno3, Balázs Vince Nagy1,4, Patrícia Lobo Maia3, Kallene Summer Moreira Vidal1, Rosana Cardoso Alves3, Russel J Reiter5, Fernanda Gaspar do Amaral6, José Cipolla-Neto7, Dora Fix Ventura1. 1. University of São Paulo, Department of Experimental Psychology, Institute of Psychology, São Paulo, Brazil. 2. Semmelweis University, Department of Ophthalmology, Budapest, Hungary. 3. University of São Paulo, Department of Neurology, Faculty of Medicine, São Paulo, Brazil. 4. Budapest University of Technology and Economics, Department of Mechatronics, Optics and Engineering Informatics, Budapest, Hungary. 5. University of Texas, Department of Cellular and Structural Biology, San Antonio, Texas, United States. 6. Federal University of São Paulo, Department of Physiology, São Paulo, Brazil. 7. University of São Paulo, Department of Physiology and Biophysics, Institute of Biomedical Sciences, São Paulo, Brazil.
Abstract
Purpose: Smith-Magenis syndrome (SMS) causes sleep disturbance that is related to an abnormal melatonin profile. It is not clear how the genomic disorder leads to a disturbed synchronization of the sleep/wake rhythm in SMS patients. To evaluate the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system, the transducers of the light-inhibitory effect on pineal melatonin synthesis, we recorded pupillary light responses (PLR) in SMS patients. Methods: Subjects were SMS patients (n = 5), with molecular diagnosis and melatonin levels measured for 24 hours and healthy controls (n = 4). Visual stimuli were 1-second red light flashes (640 nm; insignificant direct ipRGC activation), followed by a 470-nm blue light, near the melanopsin peak absorption region (direct ipRGC activation). Blue flashes produce a sustained pupillary constriction (ipRGC driven) followed by baseline return, while red flashes produce faster recovery. Results: Pupillary light responses to 640-nm red flash were normal in SMS patients. In response to 470-nm blue flash, SMS patients had altered sustained responses shown by faster recovery to baseline. SMS patients showed impairment in the expected melatonin production suppression during the day, confirming previous reports. Conclusions: SMS patients show dysfunction in the sustained component of the PLR to blue light. It could explain their well-known abnormal melatonin profile and elevated circulating melatonin levels during the day. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. This retinal dysfunction might be related to a deficit in melanopsin-based photoreception, but a deficit in rod function is also possible.
Purpose: Smith-Magenis syndrome (SMS) causes sleep disturbance that is related to an abnormal melatonin profile. It is not clear how the genomic disorder leads to a disturbed synchronization of the sleep/wake rhythm in SMSpatients. To evaluate the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system, the transducers of the light-inhibitory effect on pineal melatonin synthesis, we recorded pupillary light responses (PLR) in SMSpatients. Methods: Subjects were SMSpatients (n = 5), with molecular diagnosis and melatonin levels measured for 24 hours and healthy controls (n = 4). Visual stimuli were 1-second red light flashes (640 nm; insignificant direct ipRGC activation), followed by a 470-nm blue light, near the melanopsin peak absorption region (direct ipRGC activation). Blue flashes produce a sustained pupillary constriction (ipRGC driven) followed by baseline return, while red flashes produce faster recovery. Results: Pupillary light responses to 640-nm red flash were normal in SMSpatients. In response to 470-nm blue flash, SMSpatients had altered sustained responses shown by faster recovery to baseline. SMSpatients showed impairment in the expected melatonin production suppression during the day, confirming previous reports. Conclusions: SMSpatients show dysfunction in the sustained component of the PLR to blue light. It could explain their well-known abnormal melatonin profile and elevated circulating melatonin levels during the day. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. This retinal dysfunction might be related to a deficit in melanopsin-based photoreception, but a deficit in rod function is also possible.
Authors: Harrison McAdams; Aleksandra Igdalova; Manuel Spitschan; David H Brainard; Geoffrey K Aguirre Journal: Invest Ophthalmol Vis Sci Date: 2018-11-01 Impact factor: 4.799
Authors: Mirjam Münch; Anna Wirz-Justice; Steven A Brown; Thomas Kantermann; Klaus Martiny; Oliver Stefani; Céline Vetter; Kenneth P Wright; Katharina Wulff; Debra J Skene Journal: Clocks Sleep Date: 2020-02-28