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Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model

  • Retinal Disorders
  • Published:
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An Erratum to this article was published on 08 June 2010

Abstract

Background

Bone spicule pigments (BSP) are a hallmark of retinitis pigmentosa (RP). In this study, we examined the process of BSP formation in the rhodopsin knockout (rho -/-) mouse, a murine model for human RP.

Methods

In rho -/- mice from 2 to 16 months of age, representing the range from early to late stages of degeneration, retinal sections and whole mounts were examined morphologically by light and electron microscopy. The results were compared to scanning laser ophthalmoscopy of BSP degeneration in human RP.

Results

After the loss of all photoreceptor cells in rho-/- mice, the outer retina successively degenerated, leading to approximation and finally a direct contact of inner retinal vessels and the retinal pigment epithelium (RPE). We could show that it was the event of proximity of retinal vessel and RPE that triggered migration of RPE cells along the contacting vessels towards the inner retina. Ultrastructurally, these mislocalized RPE cells partially sealed the vessels by tight junction linkage and deposited extracellular matrix perivascularly. Also, the vascular endothelium developed fenestrations similar to the RPE-choroid interface. In whole mounts, the pigmented cell clusters outlining retinal capillaries correlated well with BSPs in human RP. The structure of the inner retina remained well preserved, even in late stages.

Conclusions

The Rho -/- mouse is the first animal model that depicts all major pathological changes, even in the late stages of RP. Using the rho -/- mouse model we were able to analyze the complete dynamic process of BSP formation. Therefore we conclude that: (1) In rho -/- retinas, BSPs only form in areas devoid of photoreceptors; (2) Direct contact between inner retinal vessels and RPE appears to be a major trigger for migration of RPE cells; (3) The distribution of the RPE cells in BSPs reflects the vascular network at the time of formation. The similarity of the disease process between mouse and human and the possibility to study all consecutive steps of the course of the disease makes the rho -/- mouse valuable for further insights in the dynamics of BSP formation in human RP.

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Acknowledgements

The authors thank Dr. Dominik Fischer for the SLO investigation.

Financial interest

None.

Author information

Author notes

  1. Andreas Gießl

    Present address: Dept. of Biology and Animal Physiology, University of Erlangen-Nuernberg, Erlangen, Germany

Authors and Affiliations

  1. Ocular Neurodegeneration Research Group, Institute for Ophthalmic Research, Tuebingen, Germany

    M. D. Fisher & M. W. Seeliger

  2. University Eye Hospital Tuebingen, Centre for Ophthalmology, Schleichstr. 12, 72076, Tuebingen, Germany

    Gesine B. Jaissle & Peter Szurman

  3. Department of Anatomy, TU Dresden, Dresden, Germany

    Christian Albrecht May

  4. Neuromedical Genetics, Netherlands Inst. for Neuroscience, Amsterdam, The Netherlands

    Serge A. van de Pavert & Jan Wijnholds

  5. Laboratory of Retinal Cell Biology, University Hospital Zürich, Zürich, Switzerland

    Andreas Wenzel

  6. Max Planck Institute for Brain Research, Frankfurt/Main, Germany

    Ellen Claes-May

  7. Institute for Zoology, University Mainz, Mainz, Germany

    Andreas Gießl & Uwe Wolfrum

  8. Ocular Genetics Unit, Trinity College, Smurfit Institute, Dublin, Ireland

    P. Humphries

Authors
  1. Gesine B. Jaissle
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  2. Christian Albrecht May
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  10. M. D. Fisher
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Corresponding author

Correspondence to Gesine B. Jaissle.

Additional information

Supported by DFG grants Se837/1–1, 1–2, 4–1,6–1, Wo 548/6–2, and BMBF grant 0314106.

The authors have full control of all primary data and they agree to allow Graefe′s Archive for Clinical and Experimental Ophthalmology to review their data upon request.

Gesine B. Jaissle and Christian Albrecht May contributed equally to this work

An erratum to this article can be found at http://dx.doi.org/10.1007/s00417-010-1357-2

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Jaissle, G.B., May, C.A., van de Pavert, S.A. et al. Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model. Graefes Arch Clin Exp Ophthalmol 248, 1063–1070 (2010). https://doi.org/10.1007/s00417-009-1253-9

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  • DOI: https://doi.org/10.1007/s00417-009-1253-9

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