Formation of fatty alcohols-components of meibum lipids-by the fatty acyl-CoA reductase FAR2 is essential for dry eye prevention.

Various lipids (mainly meibum lipids secreted by the meibomian glands) are present in the tear film lipid layer and play important roles in tear stability and the health of the cornea and conjunctiva. Many meibum lipids contain fatty alcohols (FAls) with chain lengths ≥C24, but the fatty acyl-CoA reductases (FARs) that produce them remain unclear. Here, using cell-based assays, we found that the two FAR isozymes (FAR1 and FAR2) show different substrate specificities: FAR1 and FAR2 are involved in the production of C16-C18 and ≥C20 FAls, respectively. Next, we generated Far2 knockout (KO) mice and examined their dry eye phenotype and meibum lipid composition. These mice showed a severe dry eye phenotype, characterized by plugged meibomian gland orifices, corneal damage, and tear film instability. The plugging was attributed to an increase in the melting point of the meibum lipids. Liquid chromatography coupled with tandem mass spectrometry revealed that FAl-containing meibum lipids (wax monoesters and types 1ω, 2α, and 2ω wax diesters) with a hydroxyl group at position 1 were almost completely absent in Far2 KO mice. The levels of di-unsaturated (O-acyl)-ω-hydroxy fatty acids were higher in Far2 KO mice than in wild type mice, but those of tri-unsaturated ones were comparable, suggesting the presence of two synthesis pathways for type 1ω wax diesters. These results indicate the importance of FAl-containing meibum lipids in the formation of a functional tear film lipid layer. In addition, our study provides clues to the molecular mechanism of the biosynthesis of meibum lipids.

Erratum: Diverse meibum lipids produced by Awat1 and Awat2 are important for stabilizing tear film and protecting the ocular surface.

[This corrects the article DOI: 10.1016/j.isci.2021.102478.].

Diverse meibum lipids produced by Awat1 and Awat2 are important for stabilizing tear film and protecting the ocular surface.

A lipid layer consisting of meibum lipids exists in the tear film and functions in preventing dry eye disease. Although the meibum lipids include diverse lipid classes, the synthesis pathway and role of each class remain largely unknown. Here, we created single and double knockout (KO and DKO, respectively) mice for the two acyl-CoA wax alcohol acyltransferases (Awat1 and Awat2) and investigated their dry eye phenotypes and meibum lipid composition. Awat2 KO and DKO mice exhibited severe dry eye with meibomian gland dysfunction, whereas Awat1 KO mice had mild dry eye. In these mice, specific meibum lipid classes were reduced: (O-acyl)-ω-hydroxy fatty acids and type 1ω wax diesters in Awat1 KO mice, wax monoesters and types 1ω and 2ω wax diesters in Awat2 KO mice, and most of these in DKO mice. Our findings reveal that Awat1 and Awat2 show characteristic substrate specificity and together produce diverse meibum lipids.

Mixed lead-tin perovskite films with >7 µs charge carrier lifetimes realized by maltol post-treatment.

Mixed lead-tin (Pb-Sn) halide perovskites with optimum band gaps near 1.3 eV are promising candidates for next-generation solar cells. However, the performance of solar cells fabricated with Pb-Sn perovskites is restricted by the facile oxidation of Sn(ii) to Sn(iv), which induces self-doping. Maltol, a naturally occurring flavor enhancer and strong metal binding agent, was found to effectively suppress Sn(iv) formation and passivate defects in mixed Pb-Sn perovskite films. When used in combination with Sn(iv) scavenging, the maltol surface treatment led to high-quality perovskite films which showed enhanced photoluminescence intensities and charge carrier lifetimes in excess of 7 µs. The scavenging and surface treatments resulted in highly reproducible solar cell devices, with photoconversion efficiencies of up to 21.4% under AM1.5G illumination.

Sn(IV)-free tin perovskite films realized by in situ Sn(0) nanoparticle treatment of the precursor solution.

The toxicity of lead perovskite hampers the commercialization of perovskite-based photovoltaics. While tin perovskite is a promising alternative, the facile oxidation of tin(II) to tin(IV) causes a high density of defects, resulting in lower solar cell efficiencies. Here, we show that tin(0) nanoparticles in the precursor solution can scavenge tin(IV) impurities, and demonstrate that this treatment leads to effectively tin(IV)-free perovskite films with strong photoluminescence and prolonged decay lifetimes. These nanoparticles are generated by the selective reaction of a dihydropyrazine derivative with the tin(II) fluoride additive already present in the precursor solution. Using this nanoparticle treatment, the power conversion efficiency of tin-based solar cells reaches 11.5%, with an open-circuit voltage of 0.76 V. Our nanoparticle treatment is a simple and broadly effective method that improves the purity and electrical performance of tin perovskite films.