September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Absence of collagen XVIII in mice causes age-related insuffiency in retinal pigment epithelium proteostasis
Author Affiliations & Notes
  • Niko Kivinen
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Szabolcs Felszeghy
    Department of Anatomy, Histology and Embryology, University of Debrecen, Debrecen, Hungary
  • Mari Aikio
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland
    Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
  • kati kinnunen
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
  • Niko Setälä
    Department of Ophthalmology, Central Finland Central Hospital, Jyväskylä, Finland
  • Taina Pihlajaniemi
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Oulu, Finland
    Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
  • Anu Kauppinen
    School of Pharmacy, University of Eastern Finland, Kuopio, Finland
  • Kai Kaarniranta
    Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
    Department of Ophthalmology, University of Eastern Finland, Kuopio, Finland
  • Footnotes
    Commercial Relationships   Niko Kivinen, None; Szabolcs Felszeghy, None; Mari Aikio, None; kati kinnunen, None; Niko Setälä, None; Taina Pihlajaniemi, None; Anu Kauppinen, None; Kai Kaarniranta, None
  • Footnotes
    Support  Evald and Hilda Nissi Foundation Grant 2014
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6532. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Niko Kivinen, Szabolcs Felszeghy, Mari Aikio, kati kinnunen, Niko Setälä, Taina Pihlajaniemi, Anu Kauppinen, Kai Kaarniranta; Absence of collagen XVIII in mice causes age-related insuffiency in retinal pigment epithelium proteostasis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6532.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Collagen XVIII, which has the structural properties of both collagen and proteoglycan, is a part of basement membranes (BMs). It has been found at the basement membrane/stromal interface and is thought to mediate their attachment. Endostatin, a fragment from Collagen XVIII C-terminal end which is released via proteolytic cleavage, has been reported to have anti-angiogenic effects. Age-related loss of vision in the collagen XVIII mutant mice is accompanied with pathological accumulation of deposits under the retinal pigment epithelium. We recently showed that impaired proteasomal and autophagy clearance associate with the pathogenesis of age-related macular degeneration. In this study we examined quantitatively the staining levels of both proteasomal and autophagy markers in the retinal pigment epithelium (RPE) of different ages of the Col18a1−/− mice.

Methods : Eyes from 3, 12 and 18 months old mice were enucleated and embedded in paraffin according to a routine protocol. Sequental 5 μm-thick parasagittal samples were immunostained for autophagy markers SQSTM1/p62 and Beclin proteasomal ubiquitin (Ub). The extent of immunopositivity in the retinal pigment epithelium (RPE) cells was evaluated during confocal microscopic analysis.

Results : Collagen XVIII knock-outs tissue of interest showed age-related RPE degeneration and accumulation of drusen-like deposits. Ub protein conjugate staining was prominent in both RPE cytoplasm and extracellular space whereas SQSTM1/p62 and beclin stainings were prominent in the basal part of RPE cell cytoplasm in the Col18a1−/− mice.

Conclusions : Distressed proteostasis regulated by collagen XVIII might be responsible for RPE degeneration, increased protein aggregation and finally lead to choroidal neovascularization.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×