Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by a severe autosomal recessive genetic disorder of the central nervous (CNS) and peripheral nervous system (PNS), affecting children and young adults. Its onset is before 25 years of age, with mean ages of onset and death between 11 and 38 years, respectively. The incidence is 1 in 30,000-50,000 persons. It is caused, in 97% of cases, by a homozygous guanine-adenine-adenine (GAA) trinucleotide mutation in the first intron of the frataxin (FXN) gene on chromosome 9 (9q13-q1.1). The mutation of this gene causes a deficiency of frataxin, which induces an altered inflow of iron into the mitochondria, increasing the nervous system's vulnerability to oxidative stress. The main clinical signs include spinocerebellar ataxia with sensory loss and disappearance of deep tendon reflexes, cerebellar dysarthria, cardiomyopathy, and scoliosis. Diabetes, hearing loss, and pes cavus may also occur, and although most patients with FRDA do not present with symptomatic visual impairment, 73% present with clinical neuro-ophthalmological alterations such as optic atrophy and altered eye movement, among others. This review provides a brief overview of the main aspects of FRDA and then focuses on the ocular involvement of this pathology and the possible use of retinal biomarkers.
The neurodegenerative disease amyotrophic lateral sclerosis (ALS) affects the spinal cord, brain stem, and cerebral cortex. In this pathology, both neurons and glial cells are affected. However, few studies have analyzed retinal microglia in ALS models. In this study, we quantified the signs of microglial activation and the number of retinal ganglion cells (RGCs) in an SOD1G93A transgenic mouse model at 120 days (advanced stage of the disease) in retinal whole-mounts. For SOD1G93A animals (compared to the wild-type), we found, in microglial cells, (i) a significant increase in the area occupied by each microglial cell in the total area of the retina; (ii) a significant increase in the arbor area in the outer plexiform layer (OPL) inferior sector; (iii) the presence of cells with retracted processes; (iv) areas of cell groupings in some sectors; (v) no significant increase in the number of microglial cells; (vi) the expression of IFN-γ and IL-1ß; and (vii) the non-expression of IL-10 and arginase-I. For the RGCs, we found a decrease in their number. In conclusion, in the SOD1G93A model (at 120 days), retinal microglial activation occurred, taking a pro-inflammatory phenotype M1, which affected the OPL and inner retinal layers and could be related to RGC loss.
Amyotrophic Lateral Sclerosis/pathology , Microglia/pathology , Mutation , Retinal Ganglion Cells/pathology , Superoxide Dismutase-1/physiology , Amyotrophic Lateral Sclerosis/enzymology , Amyotrophic Lateral Sclerosis/etiology , Animals , Disease Models, Animal , Mice , Mice, Transgenic , Microglia/enzymology , Retinal Ganglion Cells/enzymology
: Background: This study compared functional and structural visual changes in Friedreich ataxia (FRDA) patients with healthy controls (HC) and correlated these changes with neurological disability. METHODS: Eight FRDA Spanish patients and eight HC were selected from 2014 to 2018. Best corrected visual acuity (BCVA), visual field (VF), optic coherence tomography (OCT), and neurological disability measured by "scale for the assessment and rating of ataxia" (SARA) were taken in a basal exploration and repeated after 6 months. A linear mixed analysis and Bonferroni p-value correction were performed. RESULTS: FRDA baseline and follow-up patients showed statistically significant decreases in BCVA, VF, and OCT parameters compared with the HC. Some of the VF measurements and most of the OCT parameters had an inverse mild-to-strong correlation with SARA. Moreover, the analysis of the ROC curve demonstrated that the peripapillary retinal nerve fiber layer (pRNFL) average thickness was the best parameter to discriminate between FRDA patients and HC. CONCLUSIONS: The follow-up study showed a progression in OCT parameters. Findings showed a sequential effect in pRNFL, ganglion cell complex (GCC), and macula. The VF and the OCT could be useful biomarkers in FRDA, both for their correlation with neurological disease as well as for their ability to evaluate disease progression.
BACKGROUND: To compare early visual changes in amyotrophic lateral sclerosis (ALS) patients with healthy controls in a baseline exploration, to follow-up the patients after 6 months, and to correlate these visual changes with neurological disability. METHODS: All patients underwent a comprehensive neurological and ophthalmological examination. A linear mixed analysis and Bonferroni p-value correction were performed, testing four comparisons as follows: Control baseline vs. control follow-up, control baseline vs. ALS baseline, control follow-up vs. ALS follow-up, and ALS baseline vs. ALS follow-up. RESULTS: The mean time from the diagnosis was 10.80 ± 5.5 months. The analysis of the optical coherence tomography (OCT) showed: (1) In ALS baseline vs. control baseline, a macular significantly increased thickness of the inner macular ring temporal and inferior areas; (2) in ALS follow-up vs. ALS baseline, a significant macular thinning in the inner and outer macular ring inferior areas; (3) in ALS follow-up vs. ALS baseline, a significant peripapillary retinal nerve fiber layer (pRNFL) thinning in the superior and inferior quadrants; and (4) ALS patients showed a moderate correlation between some OCT pRNFL parameters and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. CONCLUSION: The OCT showed retinal changes in patients with motoneuron disease and could serve as a complementary tool for studying ALS.
