Inflammation in the anterior visual pathway in multiple sclerosis:what do the animal models teach us?

A provocative and overly reductive mantra is that “the back of the eye is the front of the brain.” Retinal imaging techniques that take advantage of this ‘window’ to the central nervous system can provide valuable information regarding injury to the nervous system with relative ease and with a limited burden to patients. The retina develops embryonically as part of the neuroectoderm, is made up principally of neurons and their supporting cells, and is synaptically tied to the CNS. This has led to significant interest in using retinal health as a biomarker for brain health – given the relatively limited accessibility of brain tissue in chronic neurodegenerative diseases that progress over decades. The retina is not truly part of the CNS, and as with much of brain imaging – the grounds for asserting the pathological specificity of retinal imaging is limited. Biophotonics based methods such as optical coherence tomography indirectly provide an opportunity, while autopsy studies, histology, and immunohistochemistry predominate as the methods to collect direct pathological data. Our understanding of pathological retinal lesions characteristic of demyelinating disease, especially disease showing anterior visual pathway involvement, has grown significantly in recent years. However, much of the underlying pathobiology of injury remain unexplored. This review aims to highlight the major pathological features of the retina in multiple sclerosis, and its most used animal models (EAE and cuprizone), focusing on the role of inflammation.