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Home / Equine Research Bank / PLoS One / Osteopontin and fibronectin levels are decreased in vitreous...
PloS one2011; 6(12); e27674; doi: 10.1371/journal.pone.0027674

Osteopontin and fibronectin levels are decreased in vitreous of autoimmune uveitis and retinal expression of both proteins indicates ECM re-modeling.

Abstract: Autoimmune uveitis is an intraocular inflammation that arises through autoreactive T-cells attacking the inner eye, eventually leading to blindness. However, the contributing molecular pathomechanisms within the affected tissues remain as yet elusive. The extracellular matrix (ECM) is a highly dynamic structure that varies tremendously and influences the encompassing tissue. In order to assess ECM re-modeling in autoimmune uveitis, we investigated the expression of ECM molecules fibronectin and osteopontin in vitreous and retina samples. This was carried out in the only spontaneous animal model for human autoimmue uveitis, namely equine recurrent uveitis (ERU) that resembles the human disease in clinical as well as in immunopathological aspects. ERU is a naturally occurring autoimmune disease in horses that develops frequently and has already proved its value to study disease-related pathomechanisms. Western blot analysis of fibronectin and osteopontin in healthy and uveitic vitreous revealed significant reduction of both proteins in uveitis. Immunohistochemical expression of fibronectin in healthy retinas was restricted to the inner limiting membrane abutting vimentin positive Müller cell endfeet, while in uveitic sections, a disintegration of the ILM was observed changing the fibronectin expression to a dispersed pattern extending toward the vitreous. Retinal expression of osteopontin in control tissue was found in a characteristic Müller cell pattern illustrated by co-localization with vimentin. In uveitic retinas, the immunoreactivity of osteopontin in gliotic Müller cells was almost absent. The ability of Müller cells to express fibronectin and osteopontin was additionally shown by immunocytochemistry of primary cultured equine Müller cells and the equine Müller cell line eqMC-7. In conclusion, severe ECM re-modeling in autoimmune uveitis reported here, might affect the adhesive function of fibronectin and thus the anchoring of Müller cell endfeet to the ILM. Furthermore, the absence of osteopontin in gliotic Müller cells might represent reduced neuroprotection, an osteopontin attribute that is intensively discussed.
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Publication Date: 2011-12-14 PubMed ID: 22194789PubMed Central: PMC3237414DOI: 10.1371/journal.pone.0027674Google Scholar: Lookup
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  • Journal Article
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study examines how autoimmune uveitis, a specific form of eye inflammation, decreases the levels of proteins fibronectin and osteopontin in the eye, causing changes in the extracellular matrix (ECM) of the retina, a structure vital for overall eye health.

Study Overview and Methodology

  • The research focuses on autoimmune uveitis, an intraocular condition wherein autoreactive T-cells attack the eye’s interior, potentially causing blindness.
  • The exact molecular factors within the impacted tissues that contribute to this disease are still largely unknown.
  • Vital to this exploration is the extracellular matrix (ECM), a structure influencing the encompassing tissue that sees tremendous variance and is highly dynamic.
  • The researchers conducted their experiments using the equine recurrent uveitis (ERU), an autoimmune disease that occurs naturally in horses. ERU was used due to its similarity with the human version of the disease, both clinically and immunopathologically.
  • Researchers observed the expression of fibronectin and osteopontin, two ECM molecules, in vitreous and retina samples.

Findings

  • Analysis revealed significant reductions in fibronectin and osteopontin in vitreous affected by uveitis.
  • Under normal circumstances, fibronectin expression in the retina is limited to the inner limiting membrane. However, in uveitis-affected samples, the ILM disintegrated, causing the fibronectin expression pattern to disperse towards the vitreous.
  • Osteopontin expression in healthy retina followed a specific pattern, via co-localization with vimentin; in the uveitis-affected retinas, osteopontin immunoreactivity was nearly nonexistent.

Implications and Conclusion

  • This research suggests that severe ECM remodeling occurs in cases of autoimmune uveitis, which might impact the adhesive function of fibronectin and, as a result, alter the anchoring of Müller cells to the ILM.
  • Moreover, the almost complete absence of osteopontin in Müller cells affected by gliosis may indicate a reduction in neuroprotection, a role typically associated with osteopontin. This absence may be what causes the ECM remodeling.
  • These findings may influence the development of novel treatments or preventive measures for degenerative retinal diseases like autoimmune uveitis.

Cite This Article

APA
Deeg CA, Eberhardt C, Hofmaier F, Amann B, Hauck SM. (2011). Osteopontin and fibronectin levels are decreased in vitreous of autoimmune uveitis and retinal expression of both proteins indicates ECM re-modeling. PLoS One, 6(12), e27674. https://doi.org/10.1371/journal.pone.0027674

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 6
Issue: 12
Pages: e27674

Researcher Affiliations

Deeg, Cornelia A
  • Institute of Animal Physiology, Department of Veterinary Sciences, Ludwig-Maximilians University, München, Germany. deeg@tiph.vetmed.uni-muenchen.de
Eberhardt, Christina
    Hofmaier, Florian
      Amann, Barbara
        Hauck, Stefanie M

          MeSH Terms

          • Animals
          • Autoimmune Diseases / metabolism
          • Autoimmune Diseases / pathology
          • Cells, Cultured
          • Down-Regulation
          • Extracellular Matrix / metabolism
          • Fibronectins / metabolism
          • Horses
          • Humans
          • Immunohistochemistry
          • Osteopontin / metabolism
          • Recurrence
          • Retina / metabolism
          • Retina / pathology
          • Up-Regulation
          • Uveitis / metabolism
          • Uveitis / pathology
          • Vimentin / metabolism
          • Vitreous Body / metabolism
          • Vitreous Body / pathology

          Conflict of Interest Statement

          Competing Interests: The authors have declared that no competing interests exist.

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          Citations

          This article has been cited 13 times.
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