Adipose mesenchymal stem cell-derived extracellular vesicles reduce glutamate-induced excitotoxicity in the retina.

Adipose mesenchymal stem cells (ADSCs) have protective effects against glutamate-induced excitotoxicity, but ADSCs are limited in use for treatment of optic nerve injury. Studies have shown that the extracellular vesicles (EVs) secreted by ADSCs (ADSC-EVs) not only have the function of ADSCs, but also have unique advantages including non-immunogenicity, low probability of abnormal growth, and easy access to target cells. In the present study, we showed that intravitreal injection of ADSC-EVs substantially reduced glutamate-induced damage to retinal morphology and electroretinography. In addition, R28 cell pretreatment with ADSC-EVs before injury inhibited glutamate-induced overload of intracellular calcium, downregulation of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPAR) subunit GluA2, and phosphorylation of GluA2 and protein kinase C alpha in vitro. A protein kinase C alpha agonist, 12-O-tetradecanoylphorbol 13-acetate, inhibited the neuroprotective effects of ADSC-EVs on glutamate-induced R28 cells. These findings suggest that ADSC-EVs ameliorate glutamate-induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation.

Cell cycle kinases (AUKA, CDK1, PLK1) are prognostic biomarkers and correlated with tumor-infiltrating leukocytes in HBV related HCC.

Hepatocellular carcinoma (HCC) is one of the high incidence cancers and third leading cause of cancer-related mortality. HBV is the top most risk factor accounting for 50-80% of the HCC cases. Kinases: Aurora kinase A (AURKA), cyclin-dependent kinase (CDK1) and Polo-like kinase 1 (PLK1), the key regulators of cell mitosis are overexpressed in varieties of cancers including HCC. However, the exact role of these genes in prognosis of HCC is not fully unveiled. In addition, there is no such an accurate prognostic biomarker for HBV-related HCC. To address this issue, we performed a multidimensional analysis of AURKA, CDK1 and PLK1 with a series of publicly available databases in multiple cancers and with experimental validation in HBV-related HCC tissues. Overexpression of AURKA, CDK1 and PLK1 was found in multiple cancers including HCC. Elevated expression of these genes could result from lowered DNA methylation and genomic alterations. Transcriptional overexpression was significantly correlated with poor prognosis of HCC patients. The expression levels were also significantly positively associated with tumor grades and stages. Furthermore, the expression levels of these genes had a strong correlation with infiltration of immune cells. Our analysis shows that AURKA, CDK1 and PLK1 are correlated with immune infiltration and are the prognostic biomarkers for HBV-induced HCC.Communicated by Ramaswamy H. Sarma.

Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives.

Glaucoma is a common blinding eye disease characterized by progressive loss of retinal ganglion cells (RGCs) and their axons, progressive loss of visual field, and optic nerve atrophy. Autophagy plays a pivotal role in the pathophysiology of glaucoma and is closely related to its pathogenesis. Targeting autophagy and blocking the apoptosis of RGCs provides emerging guidance for the treatment of glaucoma. Here, we provide a systematic review of the mechanisms and targets of interventions related to autophagy in glaucoma and discuss the outlook of emerging ideas, techniques, and multidisciplinary combinations to provide a new basis for further research and the prevention of glaucomatous visual impairment.

Morphological Characteristics Predict Postoperative Outcomes After Vitrectomy in Myopic Traction Maculopathy Patients.

BACKGROUND AND OBJECTIVES: To provide the surgical indication for patients with myopic traction maculopathy (MTM) by investigating the postoperative outcomes after vitrectomy among different types of morphological characteristic groups. PATIENTS AND METHODS: This was a retrospective cohort study that included patients (37 eyes) diagnosed with MTM at a single institution. All 37 eyes from 37 patients with MTMs were classified into three groups: foveal retinoschisis (FS), lamellar macular hole (LMH), and foveal retinal detachment (FRD). The ratios of anatomic recovery, central retinal thickness (CRT), and best-corrected visual acuity (BCVA) were statistically analyzed among the three groups preoperatively and at 1, 3, 6, and 12 months after vitrectomy. RESULTS: Anatomical recovery could be found in all patients of the FS group at 6 months postoperatively and in the LMH group at 12 months postoperatively. Only 83.33% patients in the FRD group showed anatomic recovery until 12 months. The time taken for CRT to reduce to 200 µm was gradually increased between the FS, LMH, and FRD groups. Postoperative BCVA was better in the FS group than the LMH and FRD groups (P < .05), but the LMH and FDR groups had no difference (P ≥ .05) at any point. The visual acuity was significantly improved in the FS group (P < .01) and FRD group (P = .018), but not in the LMH group (P = .196) at 12 months postoperatively. CONCLUSIONS: The FS group achieved anatomical recovery in the shortest time and had the best postoperative BCVA. FRD patients could get visual gain but need too much time for the anatomical recovery. LMH patients experienced anatomic success with surgery, but not in BCVA. Early surgery might be considered for eyes at FS prior to the occurrence of LMH or FRD. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:574-582.].