September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Altered autophagy flux in granular corneal dystrophy type 2
Author Affiliations & Notes
  • Eung Kweon Kim
    Yonsei University, Seoul, Korea (the Republic of)
    Corneal Dystrophy Research Institute, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Eung Kweon Kim, None
  • Footnotes
    Support  National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2011-0028699)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Eung Kweon Kim; Altered autophagy flux in granular corneal dystrophy type 2. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Presentation Description : Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disorder caused by a point mutation in transforming growth factor-β induced gene h3 (TGFBI). Mutant TGFBIp extensively colocalized with microtubule-associated protein 1 light chain 3b (MAP1LC3B, hereafter referred to as LC3)-enriched cytosolic vesicles in primary cultured GCD2 corneal fibroblasts. We observed that TGFBIp was degraded by autophagy, but not by the ubiquitin/proteasome-dependent pathway. We recently found that the autophagic clearance of mutant-TGFBIp is delayed in GCD2 corneal fibroblasts; however, any potential correlation between mutant-TGFBIp turnover and the autophagy-lysosome pathway has yet to be elucidated. The data described in the present study provide strong evidence that while autophagy is induced in GCD2 corneal fibroblasts expressing mutant-TGFBIp, its activation still might be insufficient to facilitate complete removal of mutant-TGFBIp. The induction of high levels of autophagy by a drug such as rapamycin could enhance removal of the aggregation-prone mutant-TGFBIp protein and attenuate its toxicity. These findings indicate that an insufficient autophagy-lysosome pathway might be responsible for the intracellular accumulation of mutant-TGFBIp during the pathogenesis of GCD2.

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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