Pterygium is one of the most common ocular surface diseases. During the initiation of pterygium, resting epithelial cells are activated and exhibit aberrant apoptosis and cell proliferation. Mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth, cell proliferation, protein synthesis, autophagy and transcription. However, the effect of mTORC1 activation in epithelial cells on pterygium development has not yet been reported. Additionally, the roles of mTORC1 in aberrant apoptosis and cell proliferation during the initiation of pterygium, and the underlying mechanisms, are not known. Herein, we evaluated mTOR signalling in pterygium growth and development. The results revealed that mTOR signalling, especially mTORC1 signaling, is highly activated, and aberrant apoptosis and cell proliferation were observed in pterygium. mTORC1 activation inhibits apoptosis in pterygium by regulating Beclin 1-dependent autophagy via targeting Bcl-2. mTORC1 also negatively regulates fibroblast growth factor receptor 3 (FGFR3) through inhibition of p73, thereby stimulating cell proliferation in pterygium. These data demonstrate that mTORC1 signalling is highly activated in pterygium and provide new insights into the pathogenesis and progression of pterygium. Hence, mTORC1 may be a novel therapeutic target for the treatment of pterygium.

Serum miR-126 can serve as a non-invasive biomarker for screening retinal endothelial injury and early diagnosis PDR.

As a specific microvascular complication of diabetes, diabetic retinopathy (DR) causes severe visual impairment in patients with diabetes. The expression of microRNA-126 (miRNA/miR-126) has previously been found to be significantly decreased in the serum of patients with DR. In the present study, the functions of miR-126 and its mechanisms of action in experimental diabetic retinopathy were examined in rats with streptozotocin (STZ)-induced diabetes and in high glucose (HG)-induced human retinal capillary endothelial cells (HRCECs). In vivo , diabetic rat models were established and the rats were intravitreally injected with lentivirus expressing rno-miR-126 (lenti-miR-126) or negative control (lenti-NC). RT-qPCR was used to determine the miR-126 level in the serum and retina. Paraffin sections and retinal vasculature were used to determine the extent of retinopathy. The protein content of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the retina was used as an auxiliary measurement of retinopathy. Western blot analysis and immunofluorescence staining were used to measure the expression of polo-like kinase 4 (PLK4) in rat retinal tissue. In vitro , the cells were transfected with miR-126 inhibitor or mimic and treated with the PLK4 inhibitor, CFI-400945 fumarate. RT-qPCR and western blot analysis were used to detect the miR-126 level and PLK4 expression. Cell proliferation and migration were measured by EdU and Transwell assays. The diabetic rats were found to exhibit downregulated serum and retinal miR-126 levels compared with the non-diabetic rats. The intravitreal delivery of miR-126 alleviated retinopathy and reduced the diabetes-induced upregulation of PLK4 in retinal tissues. Luciferase reporter assays confirmed that PLK4 mRNA was the target of miR-126. In HG-induced HRCECs, transfection with miR-126 mimic increased the miR-126 level, whereas it downregulated that of its downstream target, PLK4, which was opposite to the effects exerted by the miR-126 inhibitor. Furthermore, miR-126 mimic and CFI-400945 fumarate reduced the HG-induced upregulation of PLK4 expression, as well as cell proliferation and migration. On the whole, the findings of the present study demonstrate that miR-126 reduces experimental diabetic retinopathy and suppresses endothelial cell proliferation and migration by targeting PLK4. Thus, miR-126 and CFI-400945 fumarate may be therapeutic targets for DR.

No abstract