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Long-term cellular and regional specificity of the photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina

  • LI LIANG (a1), YOSHIAKI KATAGIRI (a2), LUISA M. FRANCO (a2), YASUYUKI YAMAUCHI (a2) (a3), VOLKER ENZMANN (a2) (a4), HENRY J. KAPLAN (a2) and JULIE H. SANDELL (a1)...

Abstract

This study investigated the anatomical consequences of a photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Retinae were examined 2 weeks, 1, 3, and 6 months after systemic IAA injection. The retinae were processed using standard histological methods to assess the gross morphology and topographical distribution of damage, and by immunohistochemistry to examine specific cell populations in the retina. Degeneration was restricted to the photoreceptors and was most common in the ventral retina and visual streak. In damaged regions, the outer nuclear layer was reduced in thickness or eliminated entirely, with a concomitant loss of immunoreactivity for rhodopsin. However, the magnitude of the effect varied between animals with the same IAA dose and survival time, suggesting individual differences in the bioavailability of the toxin. In all eyes, the inner retina remained intact, as judged by the thickness of the inner nuclear layer, and by the pattern of immunoreactivity for protein kinase C-α (rod bipolar cells) and calbindin D-28 (horizontal cells). Müller cell stalks became immunoreactive for glial fibrillary acidic protein (GFAP) even in IAA-treated retinae that had no signs of cell loss, indicating a response of the retina to the toxin. However, no marked hypertrophy or proliferation of Müller cells was observed with either GFAP or vimentin immunohistochemistry. Thus the selective, long lasting damage to the photoreceptors produced by this toxin did not lead to a reorganization of the surviving cells, at least with survival as long as 6 months, in contrast to the remodeling of the inner retina that is observed in inherited retinal degenerations such as retinitis pigmentosa and retinal injuries such as retinal detachment.

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Corresponding author

Address correspondence and reprint requests to: Julie H. Sandell, Department of Anatomy & Neurobiology, Room R-1014, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. E-mail: jsandell@bu.edu

References

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Aonuma, H., Yamazaki, R. & Watanabe, I. (1999). Retinal cell death by light damage. Japanese Journal of Ophthalmology 43, 171179.
Ashburn, F.S. Jr., Pilkerton, A.R., Rao, N.A. & Marak, G.E. (1980). The effects of iodate and iodoacetate on the retinal adhesion. Investigative Ophthalmology & Visual Science 19, 14271432.
Barnstable, C.J. (1980). Monoclonal antibodies which recognize different cell types in the rat retina. Nature 286, 231235.
Bringmann, A., Pannicke, T., Grosche, J., Francke, M., Wiedemann, P., Skatchkov, S.N., Osborne, N.N. & Reichenbach, A. (2006). Muller cells in the healthy and diseased retina. Progress in Retinal and Eye Research 25, 397424.
Chang, M.L., Wu, C.H., Jiang-Shieh, Y.F., Shieh, J.Y. & Wen, C.Y. (2007). Reactive changes of retinal astrocytes and Muller glial cells in kainate-induced neuroexcitotoxicity. Journal of Anatomy 210, 5465.
DiLoreto, D.A. Jr., Martzen, M.R., del Cerro, C., Coleman, P.D. & del Cerro, M. (1995). Muller cell changes precede photoreceptor cell degeneration in the age-related retinal degeneration of the Fischer 344 rat. Brain Research 698, 114.
Famiglietti, E.V. & Sharpe, S.J. (1995). Regional topography of rod and immunocytochemically characterized “blue” and “green” cone photoreceptors in rabbit retina. Visual Neuroscience 12, 11511175.
Fariss, R.N., Li, Z.Y. & Milam, A.H. (2000). Abnormalities in rod photoreceptors, amacrine cells, and horizontal cells in human retinas with retinitis pigmentosa. American Journal of Ophthalmology 129, 215223.
Fisher, S.K. & Lewis, G.P. (2003). Muller cell and neuronal remodeling in retinal detachment and reattachment and their potential consequences for visual recovery: A review and reconsideration of recent data. Vision Research 43, 887897.
Francke, M., Faude, F., Pannicke, T., Uckermann, O., Weick, M., Wolburg, H., Wiedemann, P., Reichenbach, A., Uhlmann, S. & Bringmann, A. (2005). Glial cell-mediated spread of retinal degeneration during detachment: A hypothesis based upon studies in rabbits. Vision Research 45, 22562267.
Franco, L., Yamauchi, Y., Sandell, J., Rizzo, J., Ziv, R., Kaplan, H. & Enzmann, V. (2005). Electrophysiological and anatomical changes in the outer retina after iodoacetic acid injection in the rabbit. Association for Research in Vision and Ophthalmology 46, Abstract 1492.
Gargini, C., Terzibasi, E., Mazzoni, F. & Strettoi, E. (2007). Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG study. Journal of Comparative Neurology 500, 222238.
Humayun, M.S., Prince, M., de Juan, E. Jr., Barron, Y., Moskowitz, M., Klock, I.B. & Milam, A.H. (1999). Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa. Investigative Ophthalmology & Visual Science 40, 143148.
Humayun, M., Sato, Y., Propst, R. & de Juan, E. Jr. (1995). Can potentials from the visual cortex be elicited electrically despite severe retinal degeneration and a markedly reduced electroretinogram? German Journal of Ophthalmology 4, 5764.
Juliusson, B., Bergstrom, A., Rohlich, P., Ehinger, B., van Veen, T. & Szel, A. (1994). Complementary cone fields of the rabbit retina. Investigative Ophthalmology & Visual Science 35, 811818.
Kohno, H., Sakai, T. & Kitahara, K. (2006). Induction of nestin, Ki-67, and cyclin D1 expression in Muller cells after laser injury in adult rat retina. Graefes Archive for Clinical and Experimental Ophthalmology 244, 9095.
Lasansky, A. & De Robertis, E. (1959). Submicroscopic changes in visual cells of the rabbit induced by iodoacetate. Journal of Biophysics and Biochemistry Cytology 5, 245250.
Li, Z.Y., Kljavin, I.J. & Milam, A.H. (1995). Rod photoreceptor neurite sprouting in retinitis pigmentosa. Journal of Neuroscience 15, 54295438.
Liang, L., Rizzo, J. & Sandell, J. (2007). Chx10 and nestin labelling in retinitis pigmentosa. Investigative Ophthalmology & Visual Science 48, Abstract 3749.
Lyser, K.M., Li, A. & Nunez, M. (1994). Horizontal cells in the rabbit retina: Differentiation of subtypes at neonatal and postnatal stages. International Journal of Developmental Neuroscience 12, 673682.
Marc, R.E., Jones, B.W., Watt, C.B. & Strettoi, E. (2003). Neural remodeling in retinal degeneration. Progress in Retinal Eye Research 22, 607655.
Martin, P.R. & Grünert, U. (1992). Spatial density and immunoreactivity of bipolar cells in the macaque monkey retina. Journal of Comparative Neurology 323, 269287.
McKechnie, N.M. & Foulds, W.S. (1980). Recovery of the rabbit retina after light damage (preliminary observations). Graefes Archive for Clinical and Experimental Ophthalmology 212, 271283.
Milam, A.H., Li, Z.Y. & Fariss, R.N. (1998). Histopathology of the human retina in retinitis pigmentosa. Progress in Retinal Eye Research 17, 175205.
Nakajima, M., Yuge, K., Senzaki, H., Shikata, N., Miki, H., Uyama, M. & Tsubura, A. (1996). Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N-nitrosourea in the rat retina. American Journal of Pathology 148, 631641.
Noell, W.K. (1951). The effect of iodoacetate on the vertebrate retina. Journal of Cell Physiology 37, 283307.
Noell, W.K. (1953). Experimentally induced toxic effects on structure and function of visual cells and pigment epithelium. American Journal of Ophthalmology 36, 103116.
Noell, W.K., Walker, V.S., Kang, B.S. & Berman, S. (1966). Retinal damage by light in rats. Investigative Ophthalmology & Visual Science 5, 450473.
Nork, T.M., Kim, C.B., Shanmuganayagam, D., Van Lysel, M.S., Ver Hoeve, J.N. & Folts, J.D. (2006). Measurement of regional choroidal blood flow in rabbits and monkeys using fluorescent microspheres. Archive of Ophthalmology 124, 860868.
Orzalesi, N., Calabria, G.A. & Grignolo, A. (1970). Experimental degeneration of the rabbit retina induced by iodoacetic acid. A study of the ultrastructure, the rhodopsin cycle and the uptake of 14C-labeled iodoacetic acid. Experimental Eye Research 9, 246253.
O'Steen, W.K., Shear, C.R. & Anderson, K.V. (1972). Retinal damage after prolonged exposure to visible light. A light and electron microscopic study. American Journal of Anatomy 134, 521.
Pagon, R.A. (1988). Retinitis pigmentosa. Survey of Ophthalmology 33, 137177.
Peichl, L. & Bolz, J. (1984). Kainic acid induces sprouting of retinal neurons. Science 223, 503504.
Robinson, S.R. & Dreher, Z. (1990). Muller cells in adult rabbit retinae: Morphology, distribution and implications for function and development. Journal of Comparative Neurology 292, 178192.
Roof, D.J., Adamian, M. & Hayes, A. (1994). Rhodopsin accumulation at abnormal sites in retinas of mice with a human P23H rhodopsin transgene. Investigative Ophthalmology & Visual Science 35, 40494062.
Santos, A., Humayun, M.S., de Juan, E. Jr., Greenburg, R.J., Marsh, M.J., Klock, I.B. & Milam, A.H. (1997). Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis. Archive of Ophthalmology 115, 511515.
Schnitzer, J. (1985). Distribution and immunoreactivity of glia in the retina of the rabbit. Journal of Comparative Neurology 240, 128142.
Seiler, M.J., Liu, O.L., Cooper, N.G., Callahan, T.L., Petry, H.M. & Aramant, R.B. (2000). Selective photoreceptor damage in albino rats using continuous blue light. A protocol useful for retinal degeneration and transplantation research. Graefes Archive for Clinical and Experimental Ophthalmology 238, 599607.
Strettoi, E. & Pignatelli, V. (2000). Modifications of retinal neurons in a mouse model of retinitis pigmentosa. Proceedings of the National Academy of Science USA 97, 1102011025.
Tyler, N.K. & Burns, M.S. (1991). Alterations in glial cell morphology and glial fibrillary acidic protein expression in urethane-induced retinopathy. Investigative Ophthalmology & Visual Science 32, 246256.
Wasowicz, M., Morice, C., Ferrari, P., Callebert, J. & Versaux-Botteri, C. (2002). Long-term effects of light damage on the retina of albino and pigmented rats. Investigative Ophthalmology & Visual Science 43, 813820.
Winkler, B.S., Sauer, M.W. & Starnes, C.A. (2003). Modulation of the Pasteur effect in retinal cells: Implications for understanding compensatory metabolic mechanisms. Experimental Eye Research 76, 715723.
Yu, D.Y. & Cringle, S.J. (2005). Retinal degeneration and local oxygen metabolism. Experimental Eye Research 80, 745751.

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