Sodium Iodate Disrupted the Mitochondrial-Lysosomal Axis in Cultured Retinal Pigment Epithelial Cells.

Author(s) Lin, Y.C.; Horng, L.Y.; Sung, H.C.; Wu, R.T.
Journal J Ocul Pharmacol Ther
Date Published 2018 Sep
Abstract

PURPOSE: Low doses of sodium iodate (NaIO) impair visual function in experimental animals with selective damage to retinal pigment epithelium (RPE) and serve as a useful model to study diseases caused by RPE degeneration. Mitochondrial dysfunction and defective autophagy have been suggested to play important roles in normal aging as well as many neurodegenerative diseases. In this study, we examined whether NaIO treatment disrupted the mitochondrial-lysosomal axis in cultured RPE.

METHODS: The human RPE cell line, ARPE-19, was treated with low concentrations (≤500 μM) of NaIO. The expression of proteins involved in the autophagic pathway and mitochondrial biogenesis was examined with Western blot. Intracellular acidic compartments and lipofuscinogenesis were evaluated by acridine orange staining and autofluorescence, respectively. Mitochondrial mass, mitochondrial membrane potential (MMP), and mitochondrial function were quantified by MitoTracker Green staining, tetramethylrhodamine methyl ester staining, and the MTT assay, respectively. Phagocytosis and the degradation of photoreceptor outer segments (POS) were assessed by fluorescence-based approaches and Western blot against rhodopsin.

RESULTS: Treatment with low concentrations of NaIO decreased cellular acidity, blocked autophagic flux, and resulted in increased lipofuscinogenesis in ARPE-19 cells. Despite increases in protein levels of Sirtuin 1 and PGC-1α, mitochondrial function was compromised, and this decrease was attributed to disrupted MMP. POS phagocytic activities decreased by 60% in NaIO-treated cells, and the degradation of ingested POS was also impaired. Pretreatment and cotreatment with rapamycin partially rescued NaIO-induced RPE dysfunction.

CONCLUSIONS: Low concentrations of NaIO disrupted the mitochondrial-lysosomal axis in RPE and led to impaired phagocytic activities and degradation capacities.

DOI 10.1089/jop.2017.0073
ISSN 1557-7732
Citation Lin Y-, Horng L-, Sung H-, Wu R-. Sodium Iodate Disrupted the Mitochondrial-Lysosomal Axis in Cultured Retinal Pigment Epithelial Cells. J Ocul Pharmacol Ther. 2018;34(7):500-511.

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