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