Repeated Low-level Red-light Therapy: The Next Wave in Myopia Management?

SIGNIFICANCE: Exposure to long-wavelength light has been proposed as a potential intervention to slow myopia progression in children. This article provides an evidence-based review of the safety and myopia control efficacy of red light and discusses the potential mechanisms by which red light may work to slow childhood myopia progression.The spectral composition of the ambient light in the visual environment has powerful effects on eye growth and refractive development. Studies in mammalian and primate animal models (macaque monkeys and tree shrews) have shown that daily exposure to long-wavelength (red or amber) light promotes slower eye growth and hyperopia development and inhibits myopia induced by form deprivation or minus lens wear. Consistent with these results, several recent randomized controlled clinical trials in Chinese children have demonstrated that exposure to red light for 3 minutes twice a day significantly reduces myopia progression and axial elongation. These findings have collectively provided strong evidence for the potential of using red light as a myopia control intervention in clinical practice. However, several questions remain unanswered. In this article, we review the current evidence on the safety and efficacy of red light as a myopia control intervention, describe potential mechanisms, and discuss some key unresolved issues that require consideration before red light can be broadly translated into myopia control in children.

Mia40 Protein Serves as an Electron Sink in the Mia40-Erv1 Import Pathway.

A redox-regulated import pathway consisting of Mia40 and Erv1 mediates the import of cysteine-rich proteins into the mitochondrial intermembrane space. Mia40 is the oxidoreductase that inserts two disulfide bonds into the substrate simultaneously. However, Mia40 has one redox-active cysteine pair, resulting in ambiguity about how Mia40 accepts numerous electrons during substrate oxidation. In this study, we have addressed the oxidation of Tim13 in vitro and in organello. Reductants such as glutathione and ascorbate inhibited both the oxidation of the substrate Tim13 in vitro and the import of Tim13 and Cmc1 into isolated mitochondria. In addition, a ternary complex consisting of Erv1, Mia40, and substrate, linked by disulfide bonds, was not detected in vitro. Instead, Mia40 accepted six electrons from substrates, and this fully reduced Mia40 was sensitive to protease, indicative of conformational changes in the structure. Mia40 in mitochondria from the erv1-101 mutant was also trapped in a completely reduced state, demonstrating that Mia40 can accept up to six electrons as substrates are imported. Therefore, these studies support that Mia40 functions as an electron sink to facilitate the insertion of two disulfide bonds into substrates.

Rcl1 protein, a novel nuclease for 18 S ribosomal RNA production.

In all forms of life, rRNAs for the small and large ribosomal subunit are co-transcribed as a single transcript. Although this ensures the equimolar production of rRNAs, it requires the endonucleolytic separation of pre-rRNAs to initiate rRNA production. In yeast, processing of the primary transcript encoding 18 S, 5.8 S, and 25 S rRNAs has been studied extensively. Nevertheless, most nucleases remain to be identified. Here, we show that Rcl1, conserved in all eukaryotes, cleaves pre-rRNA at so-called site A(2), a co-transcriptional cleavage step that separates rRNAs destined for the small and large subunit. Recombinant Rcl1 cleaves pre-rRNA mimics at site A(2) in a reaction that is sensitive to nearby RNA mutations that inhibit cleavage in vivo. Furthermore, mutations in Rcl1 disrupt rRNA processing at site A(2) in vivo and in vitro. Together, these results demonstrate that the role of Rcl1 in eukaryotic pre-rRNA processing is identical to that of RNase III in bacteria: to co-transcriptionally separate the pre-rRNAs destined for the small and large subunit. Furthermore, because Rcl1 has no homology to other known endonucleases, these data also establish a novel class of nucleases.