Retinal Damage in Amyotrophic Lateral Sclerosis: Underlying Mechanisms

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting in a gradual loss of motor neuron function. Although ophthalmic complaints are not presently considered a classic symptom of ALS, retinal changes such as thinning, axonal degeneration and inclusion bodies have been found in many patients. Retinal abnormalities observed in postmortem human tissues and animal models are similar to spinal cord changes in ALS. These findings are not dramatically unexpected because retina shares an ontogenetic relationship with the brain, and many genes are associated both with neurodegeneration and retinal diseases. Experimental studies have demonstrated that ALS affects many "vulnerable points" of the retina. Aggregate deposition, impaired nuclear protein import, endoplasmic reticulum stress, glutamate excitotoxicity, vascular regression, and mitochondrial dysfunction are factors suspected as being the main cause of motor neuron damage in ALS. Herein, we show that all of these pathways can affect retinal cells in the same way as motor neurons. Furthermore, we suppose that understanding the patterns of neuro-ophthalmic interaction in ALS can help in the diagnosis and treatment of this disease.