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- Title
Retinal fingerprints of ALS in patients: Ganglion cell apoptosis and TDP-43/p62 misplacement.
- Authors
Pediconi, Natalia; Gigante, Ylenia; Cama, Silvia; Pitea, Martina; Mautone, Lorenza; Ruocco, Giancarlo; Ghirga, Silvia; Di Angelantonio, Silvia
- Abstract
Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neuron function. Although ophthalmic deficits are not considered a classic symptom of ALS, recent studies suggest that changes in retinal cells, similar to those in the spinal cord motor neurons, have been observed in postmortem human tissues and animal models. Methods: In this study, we examined by immunofluorescence analysis the retinal cell layers of sporadic ALS patients in post-mortem retinal slices. We evaluated the presence of cytoplasmic TDP-43 and SQSTM1/p62 aggregates, activation of the apoptotic pathway, and microglia and astrocytes reactivity. Results: We found in the retinal ganglion cell layer of ALS patients the increase of mislocalized TDP-43, SQSTM1/p62 aggregates, activation of cleaved caspase-3, and microglia density, suggesting that retinal changes can be used as an additional diagnostic tool for ALS. Discussion: The retina is considered part of the central nervous system, and neurodegenerative changes in the brain may be accompanied by structural and possibly functional changes in the neuroretina and ocular vasculature. Therefore, using in vivo retinal biomarkers as an additional diagnostic tool for ALS may provide an opportunity to longitudinally monitor individuals and therapies over time in a noninvasive and cost-effective manner.
- Subjects
RETINAL anatomy; SPINAL cord; BIOLOGICAL models; RETINAL ganglion cells; POSTMORTEM changes; ANIMAL experimentation; APOPTOSIS; MANN Whitney U Test; FUNERAL industry; T-test (Statistics); AMYOTROPHIC lateral sclerosis; DNA-binding proteins; FLUORESCENT antibody technique; RESEARCH funding; DESCRIPTIVE statistics; BIOMETRY; NEUROGLIA; DATA analysis software; MOTOR neurons; CYTOPLASM; CASPASES
- Publication
Frontiers in Aging Neuroscience, 2023, Vol 15, p1
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2023.1110520