Mitochondrial Profile and Responses to TGF-β Ligands in Keratoconus

Akhee Sarker-Nag, Audrey E.K. Hutcheon, Dimitrios Karamichos

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Purpose: Keratoconus (KC) is a complex corneal dystrophy with multifactorial etiology. Previous studies have shown evidence of mitochondrial abnormalities in KC; however, the exact cause of these abnormalities remains unknown. The aim of this study was to identify if transforming growth factor-β (TGF-β) isoforms play a role in the regulation of mitochondrial proteins in human KC cells (HKC). Materials and Methods: Human corneal fibroblasts (HCF) and HKC were isolated and cultured for 4 weeks in three different conditions: (a) Control: MEM + 10%FBS, (b) MEM + 10%FBS + TGF-β1 and (c) MEM + 10%FBS + TGF-β3. All samples were processed for mitochondrial damage analysis using real-time PCR. Results: We quantified and analyzed 84 mitochondrial and five housekeeping genes in HCFs and HKCs. Our data showed that when TGF-β1 and/or TGF-β3 were compared with control in HCFs, nine genes were significantly different; however, no genes were significantly regulated by the TGF-β isoforms in HKCs. Significant differences were also seen in seven genes when HFCs were compared with HKCs, in all three conditions. Conclusions: Overall, our data support the growing consensus that mitochondrial dysfunction is a key player in KC disease. These in vitro data show clear links between mitochondrial function and TGF-β isoforms, with TGF-β1 severely disrupting KC-mitochondrial function, while TGF-β3 maintained it, thus suggesting that TGF-β may play a role in KC-disease treatment.

Original languageEnglish
Pages (from-to)900-907
Number of pages8
JournalCurrent Eye Research
Volume41
Issue number7
DOIs
StatePublished - 2 Jul 2016

Keywords

  • Cornea
  • keratoconus
  • mitochondria
  • mitochondrial dysfunction
  • transforming growth factor-β

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