It has been reported that diets rich in antioxidants may reduce the risk for age-related disease such as glaucoma.
39 Vitamin E,
N-acetylcysteine (NAC), and resveratrol have been reported to be effective in reducing endogenous ROS production in GTM cells.
15,40 However, vitamin E is lipophilic and tends to be retained in cell membrane and failed to achieve significant intracellular concentrations. NAC is effective in reducing oxidative damage but must be given in millimolar concentration in vitro.
23 To improve efficacy and reduce side effects, a number of approaches have been used to selectively target molecules to mitochondria, including mitochondrial potential dependent and independent methods. For example, lipophilic antioxidants were delivered to mitochondria through potential gradient across the IMM by conjugating with the TPP+ (triphenylalkylphosphonium) cation.
41 However, with the accumulation of these lipophilic cations in the mitochondrial matrix, ΔΨm was disrupted. As a result, the therapeutic index of these molecules is rather low. Another method is mitochondrial potential independent. For example, gramicidin S was used as a peptide vector to improve the targeting of nitroxides to mitochondria. This approach provides an alternative to the lipophilic cation approach for targeted mitochondrial delivery.
42 In contrast to the above-mentioned approaches using vectors to deliver conventional antioxidants to mitochondria, the small peptide MTP-131 contains an amino acid sequence that allows it to freely penetrate cell membranes. It has been revealed that MTP-131 is localized to the IMM rather than in the matrix. Therefore, it was taken up into cells in a potential-independent, nonsaturable manner, and could reach GTM cells even if their ΔΨm was compromised.
15 Although its effect on GTM
3 cells was not as good as that on iHTM cells, MTP-131 may have a promising potential in preventing progressive pathogenesis in the TM tissue of POAG. We also found that the oxidative damage in GTM
3 cells is more serious than that in iHTM cells under the same conditions. Mitochondria complex I defect might make GTM
3 cells more vulnerable to oxidative stress and also contribute to the underreaction of GTM
3 cells to antioxidants.