Melanopsin System Dysfunction in Smith-Magenis Syndrome Patients

Author(s)

Salgueiro Barboni, Mirella Telles ^{[1, 2]} ; Bueno, Clarissa ^[3] ; Nagy, Balazs Vince ^{[1, 4]} ; Maia, Patricia Lobo ^[3] ; Moreira Vidal, Kallene Summer ^[1] ; Alves, Rosana Cardoso ^[3] ; Reiter, Russel J. ^[5] ; do Amaral, Fernanda Gaspar ^[6] ; Cipolla-Neto, Jose ^[7] ; Ventura, Dora Fix ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Expt Psychol, Inst Psychol, Sao Paulo - Brazil

^[2] Semmelweis Univ, Dept Ophthalmol, Budapest - Hungary

^[3] Univ Sao Paulo, Dept Neurol, Fac Med, Sao Paulo - Brazil

^[4] Budapest Univ Technol & Econ, Dept Mechatron Opt & Engn Informat, Budapest - Hungary

^[5] Univ Texas San Antonio, Dept Cellular & Struct Biol, San Antonio, TX - USA

^[6] Univ Fed Sao Paulo, Dept Physiol, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Av Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE; v. 59, n. 1, p. 362-369, JAN 2018.
• Web of Science Citations: 6

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. (AU)

• FAPESP's process: 14/26818-2 - Development and implementation of visual evaluation methods: clinical applications and animal models
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/50457-0 - Melatonin and the control of energy metabolism: basic, clinical and epidemiological research
• Grantee: José Cipolla Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/06457-5 - Scientific instrumentation in vision research studies at the Vision Laboratory of IPUSP
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• FAPESP's process: 15/22227-2 - Electrophysiological and psychophysical evaluation of visual functions: a comparative study in Alzheimer's disease, glaucomatous neuropathy and age-related macular degeneration
• Grantee: KALLENE SUMMER MOREIRA VIDAL
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/04538-3 - Dystrophin and the human visual system: study of the visual phenotypes of Duchenne muscular dystrophy patients
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/22007-5 - Optimization of the visual functional ability in patients with macular diseases using visual training programs
• Grantee: Mirella Telles Salgueiro Barboni
• Support Opportunities: Scholarships abroad - Research