Download Retinal pathology in multiple sclerosis: insight

doi:10.1093/brain/awq358
Brain 2011: 134; 1–2
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BRAIN
A JOURNAL OF NEUROLOGY
LETTER TO THE EDITOR
Retinal pathology in multiple sclerosis: insight
into the mechanisms of neuronal pathology
Fatih C. Gundogan,1 Ahmet Tas,2 Uzeyir Erdem3 and Gungor Sobaci3
1 Etimesgut Military Hospital, Department of Ophthalmology, Ankara, Turkey
2 Ankara Mevki Military Hospital, Department of Ophthalmology, Ankara, Turkey
3 Department of Ophthalmology, Gulhane Military Medical Academy, Ankara, Turkey
Correspondence to: Fatih C. Gundogan
Yayla mah. Bağc| cad. 1392 sok.
No: 4/9 Etlik-Keçiören
06018 Etlik-Ankara, Turkey
E-mail: [email protected]
Sir, We congratulate Calabresi et al. (2010) for the scientific commentary regarding retinal pathology in multiple sclerosis. The authors have excellently summarized the pathological mechanism in
multiple sclerosis in the brain and retina. We would like to make a
contribution to the retinal aspects of their comments.
Full-field flash electroretinogram is the mass electrical activity of
the retina to a flash of light. Pattern electroretinogram reflects the
retinal response to a structured, contrast-reversal stimulus, mostly
a checkerboard pattern. There have been many studies investigating the functional and structural retinal changes in the retinas of
patients with multiple sclerosis. Mostly, optical coherence tomography has been used to explore the structural changes that show
retinal nerve fibre layer thinning. This change was linked to the
retrograde axonal degeneration in ganglion cells, as the retinal
nerve fibres lack a myelin sheath.
In a recent study, we investigated the full-field flash electroretinogram changes in multiple sclerosis (Gundogan et al.,
2007). The N95 component of pattern electroretinogram originates from the ganglion cell function and many studies have shown
N95 amplitude reduction in patients with multiple sclerosis with
or without optic neuritis history. However, we found that rod
response b-wave amplitude was significantly reduced and
standard-combined response a- and b-wave implicit times were
significantly delayed in patients with multiple sclerosis. In addition,
patients with multiple sclerosis with a delayed P100 latency
(as assessed by 95% confidence interval in control subjects) had
significantly reduced cone response b-wave amplitude and, significantly delayed cone response a- and b-wave implicit times
(Gundogan et al., 2007). These findings were surprising, as
these data showed photoreceptor cell dysfunction in the retina.
The photoreceptor cell layer is the outermost layer of the retina
and retrograde transsynaptic retinal degeneration as distal as that
layer does not seem reasonable. Moreover, a study that was conducted by Hollander et al. (1984) in cat eyes, showed that pathological changes in the retina after transection of the optic nerve
were restricted to the innermost layers by light and electron microscopic examinations (Hollander et al., 1984). As mentioned by
Calebresi et al. (2010) in their commentary, Green et al. (2010)
reported a post-mortem analysis of eyes from 82 cases of multiple
sclerosis and 10 control patients. The authors reported extensive
retinal atrophy with shrunken neurons and dropout of both retinal
ganglion cells in 79% of eyes and inner nuclear layer atrophy in
40% of eyes from patients with multiple sclerosis. As Calebresi
et al. (2010) stated, the study by Green et al. (2010) is the first
description of inner nuclear cell layer loss in multiple sclerosis.
Calebresi et al. (2010) named this new finding as a ‘paradigm
shift’ in the understanding of multiple sclerosis. However, as we
mentioned above, this finding was showed in an experimental
model in 1984. The importance of the study by Green et al.
(2010) lies in the fact that this is the first study in the post-mortem
human eye.
We believe that the findings reported by Gorczyca et al. (2004)
were a cornerstone in the understanding of retinal damage
in patients with multiple sclerosis. The patients whose sera
showed the highest reactivity with 41 and 46 kD antigens had
deficiencies in visual acuity, visual fields, ophthalmoscopy and
Advance Access publication January 11, 2011
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| Brain 2011: 134; 1–2
electroretinograms. Multiple sclerosis has been associated with
pars planitis, suggesting an immunological link between the uvea
and central nervous system. Pars planitis and multiple sclerosis are
both associated with the HLA-DR15 allele. All of these findings, in
addition to our study, suggest an immune-mediated mechanism
that is responsible from the damage in the outer layers of the
retina in patients with multiple sclerosis.
References
Calabresi PA, Balcer LJ, Frohman EM. Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology. Brain 2010;
133 (Pt 6): 1575–7.
Letter to the Editor
Gorczyca WA, Ejma M, Witkowska D, Misiuk-Hojlo M, Kuropatwa M,
Mulak M, et al. Retinal antigens are recognized by antibodies present
in sera of patients with multiple sclerosis. Ophthalmic Res 2004; 36:
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Green AJ, McQuaid S, Hauser SL, Allen IV, Lyness R. Ocular pathology
in multiple sclerosis: retinal atrophy and inflammation irrespective of
disease duration. Brain 2010; 133: 1591–601.
Gundogan FC, Demirkaya S, Sobaci G. Is optical cherence tomography
really a new biomarker candidate in multiple sclerosis. A structural
and functional evaluation. Invest Ophthalmol Vis Sci 2007; 48:
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Hollander H, Bitsi S, Maffei L, Hebel R. Electroretinographic responses
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