Corneal endothelial cells often adopt a fibroblastic-like morphology in culture, a process that has been attributed to epithelial- or endothelial-to-mesenchymal transition (EMT or EndMT). Although being extensively studied in other cell types, this transition is less well characterized in the corneal endothelium. Because of their neuroectodermal origin and their in vivo mitotic arrest, corneal endothelial cells represent a particular tissue that deserves more attention. This review article presents the basic principles underlying EMT/EndMT, with emphasis on the current knowledge regarding the corneal endothelium. Furthermore, this review discusses cell culture conditions and major cell signaling pathways that have been identified as EndMT-triggering factors. Finally, it summarizes strategies that have been developed to inhibit EndMT in corneal endothelial cell culture. The review of current studies on corneal and classical EndMT highlights some research avenues to pursue in the future and underscores the need to extend our knowledge of this process in order to optimize usage of these cells in regenerative medicine.

Human corneal endothelial cells (HCECs) easily become fibroblastic-like when cultured, rendering them unsuitable for tissue engineering of the cornea. Transforming growth factor β (TGF-β) could be a key factor in this phenomenon; however, TGF-β is also known to maintain the endothelium in a quiescent state in vivo. This work aimed to compare the effects of TGF-β1 on the phenotype of HCECs during the proliferation and maturation phases. Our results show that addition of TGF-β1 during the active proliferation phase produced fibroblastic HCECs and loss of the cell junction markers ZO-1 and n-cadherin, independent from the presence of epidermal growth factor (EGF). By contrast, addition of TGF-β1 in maturation media containing few mitogens led to an endothelial phenotype and functional cell junctions as HCECs developed a high trans-endothelial resistance. Furthermore, addition of AG-1478, an epithelial growth factor receptor inhibitor, enhanced the gain of the endothelial phenotype and cell barrier function. Overall, these results show that TGF-β1 can be used to promote the formation of a typical leaky endothelial barrier during the maturation phase of cultured HCECs. A two-phase culture of HCECs using distinct proliferation and maturation media could also be key for developing ideal HCEC culture conditions.

The reaction cascade consisting of deprotection/decarboxylation/asymmetric protonation of enolic species, starting from open-chain benzyl β-oxo esters, has been studied. When carried out in the presence of catalytic amounts of cinchonine, the reaction gave optically active α-aryl ketonesThe enantioselective protonation of prostereogenic enol derivatives is conceptually simple, but the development of catalytic methods remains a challenge, especially in terms of rational design. [1] The methodologies currently in use are largely empirical and numerous parameters need to be considered. One general approach involves the generation of an enolate, which is protonated by a catalytic chiral protic source, which is in turn regenerated by an achiral stoichiometric proton donor. The generation of ketone enolates mainly makes use either of cleavage of enol ether derivatives by organometallic compounds, [2] or of nucleophilic addition to ketenes. [3] Under these conditions, high enantioselectivities can be achieved by the use of a great variety of chiral proton donors in association with achiral sources of moderate acidity. [4] The creation of two contiguous chiral centres by a sequence of asymmetric conjugated addition/protonation reactions between enones and thiols, catalysed by a chiral lithium complex, has recently been reported. [5] Another catalytic strategy utilises a transition metal with a chiral ligand for the formation of the enolic species, which can be protonated [6] or arylated [7] enantioselectively. We have used different methodologies (a photochemical activation [8,9] and a palladium-induced cascade reaction [10,11] ) to produce enolic species. The common feature of our procedures is the presence of a chiral amino alcohol in the key step, which interacts with the enolic species and promotes its enantioselective protonation. Thanks to the enol itself, the amino alcohol is regenerated, allowing its use in catalytic amounts, without any other proton source. Our preparation of optically active ketones, which starts from racemic β-oxo acids protected as benzyl β-oxo esters, corresponds to a cascade reaction involving deprotection, de- [a] with up to 75% ee. Enantio-enriched (S)-3-phenyl-2-butanone can be converted into 2-phenylpropionic acid without racemisation.carboxylation and final asymmetric protonation of the resulting enolic species. [10,11] The key step under these conditions is probably analogous to that observed with malonic acid derivative starting materials (Scheme 1). Advances in the field of asymmetric decarboxylation since the pioneering work of Marckwald [12] have been reviewed by Brunner. [13] The reaction is generally assisted by an alkaloid base (B*), allowing the formation of an ammonium carboxylate, which on decarboxylation affords an enolate, which is protonated by the ammonium group. [12Ϫ14] Naproxen derivatives can thus be prepared with ees up to 72% by use of a catalytic amount of an amide synthesised from cinchonine. [13,15] Scheme 1. Asymmetric decarboxylation of malonic derivati...

Correction for ‘Weak backbone CH⋯OC and side chain tBu⋯tBu London interactions help promote helix folding of achiral NtBu peptoids’ by G. Angelici et al., Chem. Commun., 2016, 52, 4573–4576.