Acta Neuropathologica

, Volume 132, Issue 6, pp 765–766 | Cite as

Eyeing the brain

  • M. Francesca CordeiroEmail author
Open Access

The involvement of the retina in CNS disease is increasingly recognized in the area of neurodegeneration, as there is accumulating evidence showing that similar mechanisms occur in the eye and the brain. These neuropathological processes ultimately lead to neuronal cell death and include ischaemia, inflammation, mitochondrial dysfunction (including oxidative stress), deposition of misfolded proteins, and changes in fluid dynamics [aqueous and cerebrospinal fluid (CSF)] [1, 5, 6, 9, 10, 11].

Although common to some degree in all neurodegenerative conditions, specific events are associated more closely with certain diseases. Hence, deposition and aggregation of the misfolded proteins alpha-synuclein and beta-amyloid are believed to be key in their development in Parkinson’s disease (PD) and Alzheimer’s disease (AD), respectively [4]; mitochondrial dysfunction is particularly associated with LHON (Leber’s Hereditary optic neuropathy) and PD [12]; an important element of optic neuritis and LHON is inflammation [2, 14]; both optic neuritis and glaucoma include an ischemic aetiology [3, 8]; and finally, abnormal fluid dynamics is heavily implicated in glaucoma (through intraocular pressure) [3] and AD (CSF clearance) [7]. These overlaps are illustrated in the Venn diagram above (Fig. 1).
Fig. 1

Examples of neurodegenerative eye and brain diseases illustrating overlap of key neuropathological mechanisms

This issue of Acta Neuropathologica includes a cluster of three review papers on different aspects of neurodegeneration involving the retina, from experts in ophthalmology, neuro-ophthalmology, and neuroscience and covering glaucoma [3], Alzheimer’s disease [7], and LHON [13]. In each case, they address the neuropathological mechanisms that highlight why the retina may serve as a valuable model to study brain disease. They include molecular advances, evidence for commonalities between brain and eye changes, cell death processes, and recent updates on targets for therapy. Furthermore, they promote the idea that due to its accessibility, the eye can be a tool through which disease activity and treatment response can be assessed with widespread applications for neurological disease. This cluster will hopefully be of interest to neuropathologists, ophthalmic pathologists, neuroscientists, and neurologists intrigued by how and why it might be possible to eye the brain.



The author acknowledges the Wellcome Trust for supporting research in the group for providing the funds.


  1. 1.
    Cordeiro MF, Guo L, Luong V, Harding G, Wang W, Jones HE, Moss SE, Sillito AM, Fitzke FW (2004) Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci USA 101:13352–13356CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Costello F (2014) Inflammatory optic neuropathies. Continuum (Minneap Minn) 20:816–837. doi: 10.1212/01.CON.0000453316.60013.52 Google Scholar
  3. 3.
    Davis BM, Crawley L, Pahlitzsch M, Javaid F, Cordeiro MF (2016) Glaucoma: the retina and beyond. Acta Neuropathol. doi: 10.1007/s00401-016-1609-2 Google Scholar
  4. 4.
    Dobson CM (2003) Protein folding and misfolding. Nature 426:884–890. doi: 10.1038/nature02261 CrossRefPubMedGoogle Scholar
  5. 5.
    Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V (2012) Role of apoptosis in disease. Aging (Albany NY) 4:330–349. doi: 10.18632/aging.100459 CrossRefGoogle Scholar
  6. 6.
    Guo L, Salt TE, Luong V, Wood N, Cheung W, Maass A, Ferrari G, Russo-Marie F, Sillito AM, Cheetham ME et al (2007) Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci USA 104:13444–13449. doi: 10.1073/pnas.0703707104 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hart NJ, Koronyo Y, Black KL, Koronyo-Hamaoui M (2016) Ocular indicators of Alzheimer’s: exploring disease in the retina. Acta Neuropathol. doi: 10.1007/s00401-016-1613-6 Google Scholar
  8. 8.
    Kelley RE (2006) Ischemic demyelination. Neurol Res 28:334–340. doi: 10.1179/016164106X98242 CrossRefPubMedGoogle Scholar
  9. 9.
    London A, Benhar I, Schwartz M (2013) The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol 9:44–53. doi: 10.1038/nrneurol.2012.227 CrossRefPubMedGoogle Scholar
  10. 10.
    Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 1:120–129. doi: 10.1038/35040009 CrossRefPubMedGoogle Scholar
  11. 11.
    Normando EM, Davis BM, De Groef L, Nizari S, Turner LA, Ravindran N, Pahlitzsch M, Brenton J, Malaguarnera G, Guo L et al (2016) The retina as an early biomarker of neurodegeneration in a rotenone-induced model of Parkinson’s disease: evidence for a neuroprotective effect of rosiglitazone in the eye and brain. Acta Neuropathol Commun 4:86. doi: 10.1186/s40478-016-0346-z CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Valero T (2014) Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des 20:5507–5509CrossRefPubMedGoogle Scholar
  13. 13.
    Yu-Wai-Man P, Votruba M, Burte F, La Morgia C, Barboni P, Carelli V (2016) A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathol. doi: 10.1007/s00401-016-1625-2 PubMedGoogle Scholar
  14. 14.
    Yu AK, Song L, Murray KD, van der List D, Sun C, Shen Y, Xia Z, Cortopassi GA (2015) Mitochondrial complex I deficiency leads to inflammation and retinal ganglion cell death in the Ndufs4 mouse. Hum Mol Genet 24:2848–2860. doi: 10.1093/hmg/ddv045 CrossRefPubMedPubMedCentralGoogle Scholar

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© The Author(s) 2016

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Institute of OphthalmologyUCL Institute of OphthalmologyLondonUK
  2. 2.ICORG, Imperial College LondonLondonUK
  3. 3.Imperial College NHS TrustWestern Eye HospitalLondonUK

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