Enhanced retinal responses in Huntington’s disease patients

Article type: Research Article

Authors: Pearl, Jocelynn R.^{a; b} | Heath, Laura M.^a | Bergey, Dani E.^a | Kelly, John P.^d | Smith, Corrie^g | Laurino, Mercy Y.^f | Weiss, Avery^d | Price, Nathan D.^a | LaSpada, Albert^e | Bird, Thomas D.^{c; g} | Jayadev, Suman^{c; *}

Affiliations: [a] Institute for Systems Biology, Seattle, WA, USA | [b] Molecular & Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA | [c] Department of Neurology, University of Washington, Seattle, WA, USA | [d] Department of Ophthalmology, Seattle Children’s Hospital, Seattle, WA, USA | [e] Departments of Pediatrics, Cellular & Molecular Medicine, and Neurosciences, Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA | [f] Cancer Prevention Programs, Seattle Cancer Care Alliance, Seattle, WA, USA | [g] Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA

Correspondence: [*] Correspondence to: Dr. Suman Jayadev, Department of Neurology, University of Washington, Seattle, WA, USA. E-mail: [email protected].

Abstract: Background:Huntington’s disease (HD) is a fatal progressive neurodegenerative disease characterized by chorea, cognitive impairment and psychiatric symptoms. Retinal examination of HD patients as well as in HD animal models have shown evidence of retinal dysfunction. However, a detailed retinal study employing clinically available measurement tools has not been reported to date in HD. Objective:The goal of this study was to assess retinal responses measured by electroretinogram (ERG) between HD patients and controls and evaluate any correlation between ERG measurements and stage of disease. Methods:Eighteen patients and 10 controls with inclusion criteria of ages 18–70 years (average age HD subjects: 52.1 yrs and control subjects: 51.9 yrs) were recruited for the study. Subjects with previous history of retinal or ophthalmologic disease were excluded. Retinal function was examined by full-field ERG in both eyes of each subject. Amplitudes and latencies to increasing flash intensities in both light- and dark-adaptation were measured in all subjects. Statistical analyses employed generalized estimating equations, which account for repeated measures per subject. Results:We analyzed the b-wave amplitudes of ERG response in all flash intensities and with 30 Hz flicker stimulation. We found statistically significant increased amplitudes in HD patients compared to controls at light-adapted (photopic) 24.2 and 60.9 cd.sec/m2 intensities, dark-adapted (scotopic, red flash) 0.22 cd.sec/m2 intensity, and a trend toward significance at light-adapted 30 Hz flicker. Furthermore, we found a significant increase in light-adapted ERG response from female compared to male HD patients, but no significant difference between gender amongst controls. We also noted a positive association between number of CAG repeats and ERG response at the smallest light adapted intensity (3.1 cd.sec/m2). Conclusions:ERG studies revealed significantly altered retinal responses at multiple flash intensities in subjects with an HD expansion allele compared to controls. Significant differences were observed with either light-adapted tests or the dark-adapted red flash which suggests that the enhanced responses in HD patients is specific to the cone photoreceptor pathway.

Keywords: Cone photoreceptor, electroretinogram, Huntington’s disease, retina

DOI: 10.3233/JHD-170255

Journal: Journal of Huntington's Disease, vol. 6, no. 3, pp. 237-247, 2017