Cystoid edema, neovascularization and inflammatory processes in the murine Norrin-deficient retina.
- Beck SC Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany. su.beck@uni-tuebingen.de.
- Karlstetter M Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, D-50931, Cologne, Germany.
- Garcia Garrido M Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany.
- Feng Y Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, D-68169, Mannheim, Germany.
- Dannhausen K Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, D-50931, Cologne, Germany.
- Mühlfriedel R Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany.
- Sothilingam V Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany.
- Seebauer B Institute of Medical Molecular Genetics, University of Zurich, Zurich, Switzerland.
- Berger W Institute of Medical Molecular Genetics, University of Zurich, Zurich, Switzerland.
- Hammes HP 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68169, Mannheim, Germany.
- Seeliger MW Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, Tuebingen, Germany.
- Langmann T Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, D-50931, Cologne, Germany.
- 2018-04-15
Published in:
- Scientific reports. - 2018
Animals
Blood-Retinal Barrier
Disease Models, Animal
Eye Proteins
Humans
Inflammation
Macular Edema
Mice
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Pathologic
Nerve Tissue Proteins
Retina
Retinal Degeneration
Retinal Vessels
Visual Acuity
English
Mutations in the Norrin (NDP) gene cause severe developmental blood vessel defects in the retina leading to congenital blindness. In the retina of Ndph-knockout mice only the superficial capillary network develops. Here, a detailed characterization of this mouse model at late stages of the disease using in vivo retinal imaging revealed cystoid structures that closely resemble the ovoid cysts in the inner nuclear layer of the human retina with cystoid macular edema (CME). In human CME an involvement of Müller glia cells is hypothesized. In Ndph-knockout retinae we could demonstrate that activated Müller cells were located around and within these cystoid spaces. In addition, we observed extensive activation of retinal microglia and development of neovascularization. Furthermore, ex vivo analyses detected extravasation of monocytic cells suggesting a breakdown of the blood retina barrier. Thus, we could demonstrate that also in the developmental retinal vascular pathology present in the Ndph-knockout mouse inflammatory processes are active and may contribute to further retinal degeneration. This observation delivers a new perspective for curative treatments of retinal vasculopathies. Modulation of inflammatory responses might reduce the symptoms and improve visual acuity in these diseases.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1038/s41598-018-24476-y
- PMID 29654250
- Persistent URL
- https://sonar.ch/global/documents/298802
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