ALS Linked to Neurons’ Death in Retina, a Potential Biomarker

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Amyotrophic lateral sclerosis (ALS) leads to neuron damage in an eye layer called the retina through the activation of pro-inflammatory microglia, or immune cells of the brain and spinal cord, a study in a mouse model of the disease suggests.

Consistent with previous evidence of retinal damage in ALS patients, the findings suggest that retinal changes “can serve as biomarkers for the diagnosis and monitoring of patients with ALS, and to check the efficacy of different treatments through a simple, non-invasive and less expensive form of monitoring,” Pilar Rojas, MD, one of the study’s authors, said in a press release.

Rojas is an ophthalmologist at the Hospital General Universitario Gregorio Marañón and a researcher at the Complutense University of Madrid’s Ramón Castroviejo Institute for Eye Research (IIORC).

The study, “Amyotrophic lateral sclerosis, a neurodegenerative motor neuron disease with retinal involvement,” was published in the form of a perspective in the journal Neural Regeneration Research.

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ALS causes the loss of motor neurons — the specialized nerve cells that control voluntary movements — in the spinal cord and the brain. However, a few previous studies have reported retinal damage in ALS patients without eye disease.

The retina — the innermost, light-sensitive region in the eye that sends vision signals to the brain — is increasingly considered a “window to the brain,” as it has been shown to reflect brain changes in several neurodegenerative diseases.

Previous studies evaluating retinal changes through a widely used, noninvasive method called optical coherence tomography (OCT) have detected thinner-than-normal retinal layers in ALS patients. This thinning was associated with a loss of retinal neurons called ganglion cells, which convey visual information from other retinal neurons to the rest of the brain.

While the loss of motor neurons in ALS and other neurodegenerative diseases has been associated with overly active pro-inflammatory microglia, their role in retinal damage remains poorly understood.

To address this, Rojas and her colleagues at IIORC analyzed the retina and the microglia located at that eye layer in a mouse model of ALS that carries a mutation in SOD1, a common ALS-associated gene.

Using mice at an advanced stage of disease, the researchers found microglial changes, such as morphological changes, displacement, and clustering, in the main retinal layers where they were located. Also, these cells showed pro-inflammatory markers, highlighting the presence of microglia in a pro-inflammatory state.

The team also detected a loss of retinal ganglion cells in these mice, “consistent with the damage observed in these cells in other ALS models,” the researchers wrote.

Given that previous studies showed that in the spinal cord of ALS patients, microglia are present in a pro-inflammatory state in late stages of the disease, these findings suggest that “changes occurring at the spinal cord or brain level are occurring in parallel in the retina,” the team added.

“This had been observed in the spinal cord of these patients, but not in the retina, which is a step forward, because this may be less invasive to monitor patients,” said Rosa de Hoz, MD, PhD, of the IIORC.

“We showed that ALS is a neurodegenerative disease that not only damages motor neurons but also affects retinal tissue, with microglial activation and loss of retinal ganglion cells,” the researchers wrote.

José Manuel Ramírez, a professor in ophthalmology at UCM and the director of IIORC, said, “Our group has extensively researched the retinal changes in different neurodegenerative diseases, such as Alzheimer’s.

“However, few studies have described what happens in the retina and more specifically in the microglial cells for ALS,” Ramírez added.