April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Autophagy Is Activated and Contributes to Elimination of Accumulated Mutant TGFBIp in Granular Corneal Dystrophy Type 2
Author Affiliations & Notes
  • Eung Kweon Kim
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
    Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea
  • Seung-Il Choi
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
  • Bong-Yoon Kim
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
  • Shorafidinkhuja Dadakhujaev
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
  • Hyunmi Ryu
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
  • Tae-im Kim
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
  • Kyung Eun Han
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
  • Ji Min Ahn
    Ophthalmology, Corneal Dystrophy Research Institute, Department of Ophthalmology Yonsei University College of Medicine, Seoul, Republic of Korea
  • Joo Young Kim
    Pharmacology, Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea
  • Footnotes
    Commercial Relationships  Eung Kweon Kim, None; Seung-Il Choi, None; Bong-Yoon Kim, None; Shorafidinkhuja Dadakhujaev, None; Hyunmi Ryu, None; Tae-im Kim, None; Kyung Eun Han, None; Ji Min Ahn, None; Joo Young Kim, None
  • Footnotes
    Support  National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2009-0082186) and NRF grant funded by the MEST(No. 2010-0000324)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1097. doi:
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      Eung Kweon Kim, Seung-Il Choi, Bong-Yoon Kim, Shorafidinkhuja Dadakhujaev, Hyunmi Ryu, Tae-im Kim, Kyung Eun Han, Ji Min Ahn, Joo Young Kim; Autophagy Is Activated and Contributes to Elimination of Accumulated Mutant TGFBIp in Granular Corneal Dystrophy Type 2. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1097.

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Abstract

Purpose: : To investigate the mechanism of the intracellular accumulation of mutant transforming growth factor beta induced protein (mut-TGFBIp) in granular corneal dystrophy type 2 (GCD2)

Methods: : Primary culture corneal fibroblasts were isolated from the corneas of normal subjects and granular corneal dystrophy type 2 (GCD2) patients with a homozygous mutation in TGFBI R124H. The autophagy state using LC3 as a marker and TGFBIp levels in corneal fibroblasts treated with rapamycin were analyzed by Western blot.

Results: : Intracellular accumulation of mut-TGFBIp occurred and autophagy was activated in primary cultured GCD2 corneal fibroblasts. TGFBIp was degraded by the autophagy/lysosome pathway and this degradation was important for cell survival. Rapamycin-induced autophagy increased elimination of mut-TGFBIp, whereas inhibition of autophagy significantly reduced the viability of GCD2 corneal fibroblasts relative to normal controls. However, in spite of the significant activation of basal autophagy in GCD2 corneal fibroblasts, mut-TGFBIp accumulated in autophagosomes and lysosomes and appeared for prolonged periods.

Conclusions: : This study suggests that insufficient autophagy/lysosome pathway might be responsible for the intracellular accumulation of mut-TGFBIp in GCD2 corneal fibroblasts and for GCD2 pathogenesis.

Keywords: cornea: stroma and keratocytes • degenerations/dystrophies • cornea: basic science 
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