Is retina affected in Huntington’s disease? Is optical coherence tomography a good biomarker?

Abstract

Aim of the study Comparative cross-sectional study of retinal parameters in Huntington’s disease and their evaluation as marker of disease progression. Clinical rationale for the study Huntington’s disease (HD) is a neurodegenerative disorder with dominant motor and neuropsychiatric symptoms. Involvement of sensory functions in HD has been investigated, however studies of retinal pathology are incongruent. Effect sizes of previous findings were not published. OCT data of the subjects in previous studies have not been published. Additional examination of structural and functional parameters of retina in larger sample of patients with HD is warranted. Materials and methods This is a prospective cross-sectional study that included: peripapillary retinal nerve fiber layer thickness (RNFL) and total macular volume (TMV) measured by spectral domain optical coherence tomography (OCT) of retina, Pelli-Robson Contrast Sensitivity test, Farnsworth 15 Hue Color discrimination test, ophthalmology examination and Unified Huntington’s disease Rating Scale (UHDRS). Ninety-four eyes of 41 HD patients examined in total 47 visits and 82 eyes of 41 healthy controls (HC) examined in total 41 visits were included. Analyses were performed by repeated measures linear mixed effects model with age and gender as covariates. False discovery rate was corrected by Benjamini-Hochberg procedure. Results HD group included 21 males and 20 females (age 50.6±12.0 years [mean ± standard deviation], disease duration 7.1±3.6 years, CAG triplet repeats 44.1±2.4). UHDRS Total Motor Score (TMS) was 30.0±12.3 and Total Functional Capacity 8.2±3.2. Control group (HC) included 19 males and 22 females with age 48.2±10.3 years. There was no statistically significant difference between HD and HC in age. The effect of the disease was not significant in temporal segment RNFL thickness. It was significant in the mean RNFL thickness and TMV, however not passing false discovery rate adjustment and with small effect size. In the HD group, the effect of disease duration and TMS was not significant. The Contrast Sensitivity test in HD was within normal limits and the 15-hue-test in HD did not reveal any specific pathology. Conclusions The results of our study support possible diffuse retinal changes in global RNFL layer and in macula in Huntington’s disease, however, these changes are small and not suitable as a biomarker for disease progression. We found no other structural or functional changes in retina of Huntington’s disease patients using RNFL layer and macular volume spectral domain OCT and Contrast Sensitivity Test and 15-hue-test. Clinical implications Current retinal parameters are not appropriate for monitoring HD disease progression.

Metabolomics: An Emerging “Omics” Platform for Systems Biology and Its Implications for Huntington Disease Research

“…The phenomenon of nuclear magnetic resonance (NMR) was first described in 1946 by Bloch and Purcell [123]. Atoms with an odd mass number, such as 1 H, 31 P, 15 N, 17 O, and 13 C, have the quantum property of "spin" and behave as dipoles aligning along the axis of an applied magnetic field. During relaxation after excitation, radiofrequency signals are generated, which can be expressed as a frequency spectrum that can be further converted to chemical shift values by Fourier transformation.…”

“…It is well suited for studying intact tissues, organs, and other solid or semisolid samples through solid-state NMR and magic-angle sample spinning [127][128][129][130]. Primary metabolites (compounds ubiquitous in living organisms and essential for life, such as carbohydrates, essential amino acids, and the polymers derived from them) are composed of hydrogen, carbon, nitrogen, oxygen, and phosphorus, all of which have magnetic isotopes ( 1 H, 13 C, 15 N, 17 O, 31 P) that can be detected by NMR [131]. NMR spectrometers are equipped with electromagnetic radiation (EMR) sources that can be tuned to different frequencies so that they can be used to obtain NMR spectra from different kinds of nuclei.…”

“…This in-depth comprehension opens avenues for precise and individualized interventions, potentially enhancing the effectiveness of treatments and optimizing the overall care for those impacted by Huntington's. Metabolomics emerges as a crucial field in precisely identifying distinct metabolic alterations linked to the disease [9][10][11][12][13][14][15][16][17][18].…”

“…Because a nucleus is a charged particle in motion, it will develop a magnetic field. 1 H and 13 C have nuclear spins of 1/2 and so behave similarly to a bar magnet. In the absence of a magnetic field, these nuclear spins are randomly oriented, but when a field is applied, they line up parallel to the applied field, either spin-aligned or spin-opposed [137].…”

“…One way to address peak overlapping is to perform NMR experiments with stronger magnets and higher magnetic fields, which increases spectral dispersion. The effect of overlapping peaks can also be minimized either by using two-dimensional spectroscopy, a well-established technique in metabolomics [143], or by probing alternative NMR-active nuclei, such as 31 P, 15 N, or 13 C. Whereas 1 H-NMR spectroscopy is characterized by narrow line widths and a relatively narrow chemical shift dispersion (of ~10 ppm), 13 C NMR spectroscopy has narrow line widths combined with a rather broad (~200 ppm) chemical shift dispersion. Therefore, 13 C-NMR has significantly better resolution than 1 H-NMR.…”