Retinal neovascularization (RNV) is a common pathological feature of angiogenesis‐related retinopathy. Endocan inhibition has previously been reported to suppress RNV in oxygen‐induced retinopathy (OIR); however, its molecular mechanisms remain to be elucidated. Here, we investigated the role and mechanism of endocan in OIR. We established an OIR mouse model and detected aberrant endocan overexpression in OIR mouse retinas. Endocan inhibition through small interfering RNA or a neutralizing antibody inhibited vascular endothelial growth factor‐induced cell survival, cell proliferation, and tube formation in human retinal endothelial cells in vitro and reduced the RNV area in vivo. Using RNA sequencing, a luciferase reporter assay, and bioinformatics analyses, we identified endocan as a microRNA‐181a‐5p target gene. The antiangiogenic effect of miR‐181a‐5p on RNV was verified by intravitreal injection, and we showed that this involved the extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling pathway. Collectively, our data demonstrate that miR‐181a‐5p/endocan regulates retinal angiogenesis through the ERK1/2 signaling pathway and might represent an attractive therapeutic strategy for RNV.

We read with great interest the meta-analysis by Yang et al 1 comparing re-treatment efficacy of glucocorticosteroids or intravenous immunoglobulin for patients with immunoglobulin-resistant Kawasaki disease. The results from this analysis of four cohort studies involving 52 patients treated with second intravenous immunoglobulin and 75 patients treated with glucocorticosteroid suggested that glucocorticosteroids are more effective in controlling body temperature compared with intravenous immunoglobulin and that there was no difference in the prevention of coronary artery lesions between groups. The aim of their study was to determine the optimal drug therapy for intravenous immunoglobulin-resistant Kawasaki disease; however, they only evaluated the effects of a second intravenous immunoglobulin compared with glucocorticoids as a clinical treatment for intravenous immunoglobulin-resistant Kawasaki disease. There are only two agents involved in this meta-analysis, and some other agents may also have the efficacy to improve the process of immunoglobulinresistant Kawasaki disease, such as infliximab. For reasons that are unclear, among the four selected manuscripts, two belong to the same author, 2,3 and each date is derived from the same trial of different stages. Such problems weaken the validity of the meta-analysis by Yang et al. Nevertheless, we extol Yang et al on their effort, and studies such as this meta-analysis are necessary to gain optimal re-treatment methods, which remain controversial for immunoglobulin-resistant patients. Such studies should be conducted in a way that includes broad agents and must avoid errors cautiously. Thank you very much! Best regards to you! Yuan-han Qin

Corneal neovascularization (CoNV) in response to chemical burns is a leading cause of vision impairment. Although glutamine metabolism plays a crucial role in macrophage polarization, its regulatory effect on macrophages involved in chemical burn-induced corneal injury is not known. Here, we elucidated the connection between the reprogramming of glutamine metabolism in macrophages and the development of alkali burn-induced CoNV. Glutaminase 1 (GLS1) expression was upregulated in the mouse corneas damaged with alkali burns and was primarily located in F4/80-positive macrophages. Treatment with a selective oral GLS1 inhibitor, CB-839 (telaglenastat), significantly decreased the distribution of polarized M2 macrophages in the alkali-injured corneas and suppressed the development of CoNV. In vitro studies further demonstrated that glutamine deprivation or CB-839 treatment inhibited the proliferation, adhesion, and M2 polarization of bone marrow-derived macrophages (BMDMs) from C57BL/6J mice. CB-839 treatment markedly attenuated the secretion of proangiogenic factors, including vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-BB (PDGF-BB) from interleukin-4- (IL-4-) regulated M2 macrophages. Our findings revealed that GLS1 inhibition or glutamine deprivation prevented alkali-induced CoNV by inhibiting the infiltration and M2 polarization of macrophages. This work suggests that pharmacological GLS1 inhibition is a feasible and effective treatment strategy for chemical burn-related CoNV in humans.