The retina as a window to the brain—from eye research to CNS disorders

Abstract

Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.

Key Points

  • As an extension of the CNS, the retina displays similarities to the brain and spinal cord in terms of anatomy, functionality, response to insult, and immunology

  • Several major neurodegenerative disorders have manifestations in the retina, suggesting that the eye is a 'window' into the brain

  • Neurodegenerative processes that have been characterized in CNS disorders are also detected in some classic ocular pathologies

  • The accessibility and organization of the retina makes it a convenient research tool with which to study processes in the CNS

  • Advances in ocular imaging techniques support the potential of these approaches as effective aids in noninvasive diagnosis of CNS disorders

  • Future research should be aimed at testing whether therapies that are beneficial in brain disorders could also alleviate diseases of the eye, and vice versa

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Figure 1: The eye as an extension of the CNS.
Figure 2: Ocular manifestations of neurodegenerative disorders.

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Acknowledgements

We thank S. Schwarzbaum for editorial assistance. The work of the authors is supported in part by The Glaucoma Foundation, the European Research Council Advanced Grant, and the FP7-HEALTH-2011 two-stage grant given to M. Schwartz.

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A. London and I. Benhar contributed equally to this manuscript. All authors contributed to researching data for the article, discussions of content, writing, and to the review and/or editing of the manuscript before submission.

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Correspondence to Michal Schwartz.

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London, A., Benhar, I. & Schwartz, M. The retina as a window to the brain—from eye research to CNS disorders. Nat Rev Neurol 9, 44–53 (2013). https://doi.org/10.1038/nrneurol.2012.227

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