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