April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Altered Mitochondrial Function In Type 2 Granular Corneal Dystrophy
Author Affiliations & Notes
  • Tae-im Kim
    Ophthalmology, Severance Hospital, Vision Research Inst, Seoul, Republic of Korea
  • Eung Kweon Kim
    Ophthalmology, Severance Hospital, Corneal dystrophy research institue, Seoul, Republic of Korea
  • Kyung Eun Han
    Ophthalmology, Severance Hospital, Vision Research Inst, Seoul, Republic of Korea
  • Ji Min Ahn
    Ophthalmology, Severance Hospital, Vision Research Inst, Seoul, Republic of Korea
  • Sangmin Nam
    Ophthalmology, Pundang CHA Hospital, Pochun CHA University, Sungnam, Republic of Korea
  • Footnotes
    Commercial Relationships  Tae-im Kim, None; Eung Kweon Kim, None; Kyung Eun Han, None; Ji Min Ahn, None; Sangmin Nam, None
  • Footnotes
    Support  This research was partially supported by a grant from KRIBB Research Initiative Program
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1099. doi:
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      Tae-im Kim, Eung Kweon Kim, Kyung Eun Han, Ji Min Ahn, Sangmin Nam; Altered Mitochondrial Function In Type 2 Granular Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1099.

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Abstract

Purpose: : Type 2 granular corneal dystrophy (GCD2) is caused by point mutation R124H in the β-transforming growth factor-induced gene and characterized by age-dependent progression of corneal deposits. We compared the morphology and function of mitochondria in wildtype and GCD2 mutated corneal tissues and fibroblasts, and discovered that the GCD2 mutation alters mitochondrial function, potentially explaining the age-dependent progression of the disease.

Methods: : Mitochondrial morphology in heterozygous GCD2 and normal corneal tissues was evaluated by electron microscopy. Primary corneal fibroblasts of homozygous and normal corneas were cultured to passage 4 or 8. Cells were evaluated by electron microscopy, mitotracker and cytochrome C staining, JC-1 assay, MTS and CCK-8 measurement, and western blots for expression of complex I-V and proteins involved in mitochondrial function (PGC-1α, ANT-1, VDAC, AKT, and mTOR).

Results: : Keratocytes of normal corneal tissue have a narrow shape and the details of their intracellular organelles are difficult to distinguish. Keratocytes of heterozygous GCD2 tissues displayed many degenerative mitochondria. Wildtype cultured fibroblasts had small, healthy mitochondria, whereas homozygous cells had elongated, swollen mitochondria. Mitotracker and cytochrome C staining indicated increased mitochondrial activity in mutated cells at early passages, but decreased activity at later passages. Decreases in depolarized mitochondria, cellular proliferation, and complex I-V expression were observed in late passage mutant fibroblasts. PGC-1α, ANT-1 p-AKT, and p-mTOR expression showed a passage-dependent decrease in all cells.

Conclusions: : Mitochondrial morphology and function were altered in mutated GCD2 keratocytes, particularly in older cells. The alteration of mitochondrial function is critical for understanding the pathogenesis of GCD2.

Keywords: cornea: stroma and keratocytes • mitochondria • oxidation/oxidative or free radical damage 
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