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Glatiramer acetate elevates cell production in the mature retinal pigment epithelium

Published online by Cambridge University Press:  22 December 2011

GOLNAZ SHAHABI  and
GLEN JEFFERY
GOLNAZ SHAHABI
Affiliation:
Institute of Ophthalmology, University College London, London, UK
GLEN JEFFERY*
Affiliation:
Institute of Ophthalmology, University College London, London, UK
*
*Address correspondence and reprint requests to: Glen Jeffery, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. E-mail: [email protected]
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Abstract

The retinal-pigmented epithelium (RPE) is critical for visual function. Throughout life, central RPE cells are lost but replenished by peripheral cell production. Glatiramer acetate increases neuronal production in mature brains and is thought to erode age-related deposits in the human retina that are risk factors for macular degeneration. Here, we ask whether this agent also elevates RPE production in mature rat eyes. If so, it may be used to replenish these cells in damaged eyes. Glatiramer acetate was given systemically for 14 days combined with Bromodeoxyuridine (BrdU) to mark cell division. One eye was then processed for the cell cycle marker Ki67 and the other for BrdU. Glatiramer acetate significantly elevated the number of RPE cells in the cell cycle, with more labeled with Ki67. There were also significantly more BrdU-labeled cells over the 14 days, confirming that some cells divided. However, while Ki67 positive cell numbers increased by approximately 100% following examination at one time point, BrdU cell numbers increased by only 3% when averaged per day. Hence, glatiramer acetate induces cells to proliferate, but many may fail either to complete division or to survive. This may have long-term consequences for this tissue.

Keywords

RPEProliferationCell cycleKi67BromodeoxyduridineAge-related macular degeneration
Type
Brief Communication
Information
Visual Neuroscience , Volume 28 , Issue 6 , November 2011 , pp. 543 - 546
Copyright
Copyright © Cambridge University Press 2011

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References

Adams, T., Shahabi, G., Hoh-Kam, J. & Jeffery, G. (2010). Held under arrest: Many mature albino RPE cells display polyploidal features consistent with abnormal cell cycle retention. Experimental Eye Research 90, 368–372.CrossRefGoogle ScholarPubMed
Al-Hussaini, H., Schneiders, M., Lundh, P. & Jeffery, G. (2009). Drusen are associated with local and distant disruptions to human retinal pigment epithelium cells. Experimental Eye Research 88, 610–612.CrossRefGoogle ScholarPubMed
Al-Hussaini, H., Vugler, A., Semo, M. & Jeffery, G. (2008). Mature mammalian retinal pigment epithelium cells proliferate in vivo. Molecular Vision 14, 1784–1791.Google ScholarPubMed
Butovsky, O., Koronyo-Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H. & Schwartz, M. (2006). Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proceedings of the National Academy of Sciences of the United States of America 103, 11784–11789.CrossRefGoogle ScholarPubMed
Carpintero, R., Brandt, K.L., Gruaz, L., Molnarfi, N., Lalive, PH. & Burger, D. (2010). Glatiramer acetate triggers PI3Kβ/Akt and MEK/ERK pathways to induce IL-1 receptor antagonist in human monocyte. Proceedings of the National Academy of Science, USA 107, 17692–17697.CrossRefGoogle Scholar
Cernak, I., Stoica, B., Byrnes, K.R., Di Giovanni, S. & Faden, S. (2005). Role of cell cycle in the pathobiology of central nervous system trauma. Cell Cycle 4, 1286–1293.Google Scholar
Del Priore, L.V., Kuo, Y.H. & Tezel, T.H. (2002). Age-related changes in human RPE cell density and apoptosis proportion in situ. Investigative Ophthalmology and Visual Science 43, 3312–3318.Google ScholarPubMed
Gao, H. & Hollyfield, J.G. (1992). Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells. Investigative Ophthalmology and Visual Science 33, 1–17.Google ScholarPubMed
Green, W.R. (1999). Histopathology of age-related macular degeneration. Molecular Vision 5, 27.Google ScholarPubMed
Harman, A.M., Fleming, P.A., Hoskins, R.V. & Moore, S.A. (1997). Development and ageing of cell topography in the human retinal pigment epithelium. Investigative Ophthalmology and Visual Science 38, 2016–2026.Google Scholar
Hollyfield, J.G. (2010). Age-related macular degeneration: the molecular link between oxidative damage, tissue specific inflammation and outer retinal disease: The Proctor lecture. Investigative Ophthalmology and Visual Science 51, 1275–1281.Google Scholar
Illia, M. & Jeffery, G. (1999). Retinal mitosis is regulated by dopa, a melanin precursor that may influence the time at which cells exit the cell cycle: analysis of patterns of cell production in pigmented and albino retinae. The Journal of Comparative Neurology 405, 394–405.3.0.CO;2-Y>CrossRefGoogle Scholar
Landa, G., Butovsky, O., Shoshani, J., Schwartz, M. & Pollack, A. (2008). Weekly vaccination with Copaxone (glatiramer acetate) as a potential therapy for dry age-related macular degeneration. Current Eye Research 33, 1011–1013.Google Scholar
Landa, G., Rosen, R.B., Patel, A., Lima, V.C., Tai, K.W., Perez, V.R., Aizman, A. & Garcia, P.M. (2011). Qualitative spectral OCT/SLO analysis of dursen change in dry age-related macular degeneration patients treated with copaxone. Journal of Ocular Pharmacology and Therapeutics 27, 77–82.CrossRefGoogle Scholar
Panda-Jonas, S., Jonas, J.B. & Jackobczyk-Zmija, M. (1996). Retinal pigment epithelial cell count, distribution and correlations in normal human eyes. American Journal of Ophthalmology 212, 181–189.CrossRefGoogle Scholar
Sarks, S.H. (1976). Ageing and degeneration in the macular region: A clinico-pathological study. The British Journal of Ophthalmology 60, 324–341.CrossRefGoogle ScholarPubMed
Shahabi, G., Lenassi, E. & Jeffery, G., (2011). Distorting the Mosaic: The Effect of Melanin on Ageing RPE. ARVO Meeting Presentation 3208/A456. Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL.Google Scholar
Ts’o, M.O.M. & Friedman, E. (1967). The retinal pigmented epithelium. I. Comparative histology. Archives of Ophthalmology 78, 641–649.CrossRefGoogle ScholarPubMed
Van Kaer, L. (2011). Glatiramer acetate for treatment of MS: regulatory B cells join the cast of players. Experimental Neurology 227, 19–23.Google Scholar
von Leithner, P.L., Ciurtin, C. & Jeffery, G. (2010). Microscopic mammalian retinal pigment epithelium lesions induce widespread proliferation with different magnitudes between centre and periphery. Molecular Vision 16, 570–581.Google Scholar
Yang, Y. & Herrup, K. (2007). Cell division in the CNS: Protective response or lethal event in post-mitotic neurons. Biochimica et Biophysica Acta 1772, 457–466.Google Scholar