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Detailed functional and structural characterization of a macular lesion in a rhesus macaque

Documenta Ophthalmologica volume 125, pages 179–194 (2012)Cite this article

Abstract

Purpose

Animal models are powerful tools to broaden our understanding of disease mechanisms and to develop future treatment strategies. Here we present detailed structural and functional findings of a rhesus macaque suffering from a naturally occurring bilateral macular dystrophy (BMD), partial optic atrophy and corresponding reduction of central V1 signals in visual fMRI experiments when compared to data in a healthy macaque (CTRL) of similar age.

Methods

Retinal imaging included infrared and autofluorescence recordings, fluorescein and indocyanine green angiography and spectral domain optical coherence tomography (OCT) on the Spectralis HRA + OCT platform. Electroretinography included multifocal and Ganzfeld-ERG recordings. Animals were killed and eyes analyzed by immunohistochemistry.

Results

Angiography showed reduced macular vascularization with significantly larger foveal avascular zones (FAZ) in the affected animal (FAZBMD = 8.85 mm2 vs. FAZCTRL = 0.32 mm2). OCT showed bilateral thinning of the macula within the FAZ (total retinal thickness, TRTBMD = 174 ± 9 µm) and partial optic nerve atrophy when compared to control (TRTCTRL = 303 ± 45 µm). Segmentation analysis revealed that inner retinal layers were primarily affected (inner retinal thickness, IRTBMD = 33 ± 9 µm vs. IRTCTRL = 143 ± 45 µm), while the outer retina essentially maintained its thickness (ORTBMD = 141 ± 7 µm vs. ORTCTRL = 160 ± 11 µm). Altered macular morphology corresponded to a preferential reduction of central signals in the multifocal electroretinography and to a specific attenuation of cone-derived responses in the Ganzfeld electroretinography, while rod function remained normal.

Conclusion

We provided detailed characterization of a primate macular disorder. This study aims to stimulate awareness and further investigation in primates with macular disorders eventually leading to the identification of a primate animal model and facilitating the preclinical development of therapeutic strategies.

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Acknowledgments

We would like to thank Susanne Kohl and Nicole Weisschuh for sequencing the PAX6 gene and Matthias Munk and Henry Evrardj for perfusing the BMD animal. This study was supported by the Deutsche Forschungsgesellschaft (NKL), National Eye Institute (NEI) R01 grant EY019272 (SS) and National Institute of Neurological Disorders and Stroke (NINDS) R21NS059607 (SS).

Conflict of Interest

The study sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Furthermore, the authors state that they have full control of all primary data and that they agree to allow interested parties to review their data if requested.

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Author notes

  1. M. Dominik Fischer

    Present address: Nuffield Laboratory of Ophthalmology, University of Oxford, Levels 5 and 6 West Wing, The John Radcliffe Hospital, Oxford, OX3 9DU, UK

Affiliations

  1. Centre for Ophthalmology, University Eye Hospital, Schleichstr. 12-14, 72076, Tübingen, Germany

    M. Dominik Fischer

  2. Institute for Ophthalmic Research, Centre for Ophthalmology, Schleichstr. 12-14, 72076, Tübingen, Germany

    M. Dominik Fischer, Ditta Zobor & Mathias W. Seeliger

  3. Max-Planck Institute for Biological Cybernetics, Spemannstr. 38-44, 72076, Tübingen, Germany

    Georgios A. Keliris, Yibin Shao, Nikos K. Logothetis & Stelios M. Smirnakis

  4. Neuroanatomy, Max Planck Institute for Brain Research, Deutschordenstr. 46, 60528, Frankfurt a.M., Germany

    Silke Haverkamp

  5. University Eye Clinic, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Herbert Jägle

  6. Department of Neuroscience and Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Stelios M. Smirnakis

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  1. M. Dominik Fischer
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Correspondence to M. Dominik Fischer.

Additional information

M. Dominik Fischer and Ditta Zobor have contributed equally to the manuscript.

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10633_2012_9340_MOESM1_ESM.tif

Supplemental Fig. 1 Retinal fundus autofluorescence (FAF) recordings of CTRL and BMD monkey. Signal strength differs to some degree between CTRL and BMD animals, while distribution does not demonstrate any significant pathology seen in other forms of macular dystrophies such as a bulls eye pattern of hyper-/hypo-fluorescent rings of FAF signal. (TIFF 714 kb)

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Dominik Fischer, M., Zobor, D., Keliris, G.A. et al. Detailed functional and structural characterization of a macular lesion in a rhesus macaque. Doc Ophthalmol 125, 179–194 (2012). https://doi.org/10.1007/s10633-012-9340-3

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Keywords

  • Macular disorder
  • Neurodegeneration
  • Functional MRI
  • Optical coherence tomography
  • Electroretinography