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Retinal neurodegeneration in the DBA/2J mouse—a model for ocular hypertension

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Abstract

Mice of the DBA/2J strain spontaneously develop complex ocular abnormalities, including glaucomatous loss of retinal ganglion cells (RGC). In the present study ultrastructural features of retinal neurodegeneration in DBA/2J mice of different age (3, 6, 8 and 11 months) are described. By 3 months, RGC apoptosis characterized by electron-dense karioplasm and cytoplasm of ganglion cells was observed. The occurrence of apoptotic ganglion cells peaked at the age of 6 months. Past this age, necrosis characterized by swelling and electron-rare cytoplasm appeared to be the prevailing form of cell death. Müller glia activation increased with age, but there were no signs of leukocyte infiltration. At 8 and 11 months, signs of neoangiogenesis were found both at the ultrastructural level and in clinical examinations. In these older animals myelin-like bodies, most probably representing the intracellular aggregates of phospholipids in irreversibly injured cells, were also seen. Photoreceptor cells were not affected at any age. Our observations suggest that retinal degeneration in the DBA/2J mice does not involve recruitment of blood-borne inflammatory/phagocytosing cells, and that apoptosis is gradually replaced by necrosis as the predominant pathway of RGC death. Retinal degeneration in 3- to 11-month-old DBA/2J mice partially resembles human pigment dispersion syndrome and pigmentary glaucoma with characteristic anterior segment changes and elevation of intraocular pressure. However, neovasculogenesis and myelin-like bodies are observed during aging. Therefore, the DBA/2J model requires judicious interpretation as a glaucoma model.

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Acknowledgements

This study was supported in part by the European Union under the Marie Curie Individual Fellowship to Dr. Robert Rejdak (contract number:QLK2-CT-2002-51562). Dr. Frank Schuettauf was supported by the Fortüne program (912-1-0) and the European Union (QLK6-CT-2001-00385). The authors thank Sandra Bernhard-Kurz for excellent technical assistance.

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Authors and Affiliations

  1. Experimental Ophthalmology, University Eye Hospital, Roentgenweg 11, 72076, Tuebingen, Germany

    Frank Schuettauf, Robert Rejdak, Michael Voelker, Georgios Blatsios, Kei Shinoda & Eberhart Zrenner

  2. Tadeusz Krwawicz Chair of Ophthalmology and 1st Eye Hospital, Medical University, Lublin, Poland

    Robert Rejdak & Zbigniew Zagorski

  3. Laboratory of Cell Ultrastructure, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland

    Michal Walski & Malgorzata Frontczak-Baniewicz

  4. Laboratory of Experimental Pharmacology, Medical Research Center, Polish Academy of Science, Warsaw, Poland

    Pawel Grieb

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  1. Frank Schuettauf
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Correspondence to Frank Schuettauf.

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Schuettauf, F., Rejdak, R., Walski, M. et al. Retinal neurodegeneration in the DBA/2J mouse—a model for ocular hypertension. Acta Neuropathol 107, 352–358 (2004). https://doi.org/10.1007/s00401-003-0816-9

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  • DOI: https://doi.org/10.1007/s00401-003-0816-9

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