Contributions
Abstract: P1103
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurophysiology
Objective: Test the hypothesis that the melanopsin-mediated sustained pupillary constriction response can be attenuated in the context of damage to retinal architecture.
Background: We can objectively investigate the relationship between retinal architecture and a corresponding tissue-specific neurophysiologic signature: the blue light-induced, melanopsin-mediated pupillary constriction response. Also, retinal ganglion cell neurons expressing melanopsin project to the suprachiasmatic nucleus (SCN), known as the body´s circadian clock. Understanding how retinal damage in MS changes the melanopsin-mediated pupillary response may help elucidate the impact of damage on transmission to the hypothalamus. This can potentially alter homeostatic networks associated with fatigue, cognition, mood regulation, autonomically-mediated immune system regulation, satiety, sexual behavior, neuroendocrine reflex arcs, and thermodysregulation in MS patients.
Methods: We developed a novel device capable of stimulating the retina with a restricted range of blue light in 10nm bins from 400-500nm in order to determine if blue light-induced persistent constriction responses are of variable magnitude in different MS patients when employing discrete blue light stimuli. This melanopsin-mediated response following cessation of a blue light stimulus was compared to the photoreceptor-mediated pupillary constriction following cessation of a red light stimulus. OCT was used to characterize the relation of pupillary responses to changes in retinal architecture, specifically the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL+IPL).
Results: A significant correlation between GCL+IPL thickness and duration of the melanopsin-mediated pupil constriction phase response establishes this unique response as a potential pathophysiologic signature and biomarker for understanding the relationship between structure and function of the visual system in MS.
Conclusions: Retinal damage in MS correlates with deficits in a unique blue light-specific pupillary response. We can profile individual MS patients for the stimulus characteristics of greatest response for them, and potentially fabricate glasses or other devices capable of delivering therapeutic ´epochs´ of blue light stimulation specifically optimized for each patient. Such treatment may be germane to improving a vast array of the body´s homeostatic states; and specifically those that cause significant morbidity in MS.
Disclosure: Dr. Eric Kildebeck has nothing to disclose.
Dr. Shin Beh has nothing to disclose.
Amy Conger has nothing to disclose.
Darrel Conger has nothing to disclose.
Dr. Laura Balcer has received honoraria for consulting on development of visual outcomes for MS trials from Biogen and Genzyme. She is on a clinical trial advisory board for Biogen.Shiv Saidha has nothing to disclose.
Dr. Calabresi has provided consultation services to Novartis, EMD-Serono, Teva, Biogen; and has received grant support from EMD-Serono, Teva, Biogen, Genentech, Bayer, Abbott, and Vertex.
Dr. Shiv Saidha has nothing to disclose.
Dr. Robert Rennaker has nothing to disclose.
Dr. Elliot Frohman has received speaking and consulting fees from, TEVA Neuroscience, Genzyme, Acorda, and Novartis.
Teresa Frohman has received speaker and consultant fees from Genzyme, Novartis and Acorda.
Abstract: P1103
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurophysiology
Objective: Test the hypothesis that the melanopsin-mediated sustained pupillary constriction response can be attenuated in the context of damage to retinal architecture.
Background: We can objectively investigate the relationship between retinal architecture and a corresponding tissue-specific neurophysiologic signature: the blue light-induced, melanopsin-mediated pupillary constriction response. Also, retinal ganglion cell neurons expressing melanopsin project to the suprachiasmatic nucleus (SCN), known as the body´s circadian clock. Understanding how retinal damage in MS changes the melanopsin-mediated pupillary response may help elucidate the impact of damage on transmission to the hypothalamus. This can potentially alter homeostatic networks associated with fatigue, cognition, mood regulation, autonomically-mediated immune system regulation, satiety, sexual behavior, neuroendocrine reflex arcs, and thermodysregulation in MS patients.
Methods: We developed a novel device capable of stimulating the retina with a restricted range of blue light in 10nm bins from 400-500nm in order to determine if blue light-induced persistent constriction responses are of variable magnitude in different MS patients when employing discrete blue light stimuli. This melanopsin-mediated response following cessation of a blue light stimulus was compared to the photoreceptor-mediated pupillary constriction following cessation of a red light stimulus. OCT was used to characterize the relation of pupillary responses to changes in retinal architecture, specifically the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL+IPL).
Results: A significant correlation between GCL+IPL thickness and duration of the melanopsin-mediated pupil constriction phase response establishes this unique response as a potential pathophysiologic signature and biomarker for understanding the relationship between structure and function of the visual system in MS.
Conclusions: Retinal damage in MS correlates with deficits in a unique blue light-specific pupillary response. We can profile individual MS patients for the stimulus characteristics of greatest response for them, and potentially fabricate glasses or other devices capable of delivering therapeutic ´epochs´ of blue light stimulation specifically optimized for each patient. Such treatment may be germane to improving a vast array of the body´s homeostatic states; and specifically those that cause significant morbidity in MS.
Disclosure: Dr. Eric Kildebeck has nothing to disclose.
Dr. Shin Beh has nothing to disclose.
Amy Conger has nothing to disclose.
Darrel Conger has nothing to disclose.
Dr. Laura Balcer has received honoraria for consulting on development of visual outcomes for MS trials from Biogen and Genzyme. She is on a clinical trial advisory board for Biogen.Shiv Saidha has nothing to disclose.
Dr. Calabresi has provided consultation services to Novartis, EMD-Serono, Teva, Biogen; and has received grant support from EMD-Serono, Teva, Biogen, Genentech, Bayer, Abbott, and Vertex.
Dr. Shiv Saidha has nothing to disclose.
Dr. Robert Rennaker has nothing to disclose.
Dr. Elliot Frohman has received speaking and consulting fees from, TEVA Neuroscience, Genzyme, Acorda, and Novartis.
Teresa Frohman has received speaker and consultant fees from Genzyme, Novartis and Acorda.