Diabetic retinopathy (DR) is the leading cause of blindness in patients with diabetes. However, biomarkers for early detection of DR are still lacking. MicroRNAs (miRNAs) regulate multiple biological functions and are often deregulated in DR. We aimed to investigate whether circulating miRNAs can be used as biomarkers of early-stage DR. We used RNA-seq and qRT-PCR to identify differential serum miRNAs in patients with type 2 diabetes mellitus with DR (T2DM-DR), T2DM without DR (T2DM-no-DR), and healthy controls. We validated differential circulating miRNAs in two phases using qRT-PCR assays. RNA-seq analysis identified 7 differential circulating miRNAs between T2DM-DR and T2DM-no-DR and 47 differential miRNAs between T2DM-DR and healthy subjects. Two-stage analysis verified that a profile of five serum miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, hsa-miR-28-3p, has-miR-151a-5p, has-miR-148a-3p) was significantly associated with T2DM-DR. Receiver-operator-characteristic analyses showed that a panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) presented 0.92 sensitivity and 0.94 specificity for distinguishing T2DM-DR from T2DM-no-DR, and 0.93 sensitivity and 0.86 specificity for differentiating early-stage T2DM-DR (NPDR) from late-stage DR (PDR). Lentivirus-mediated overexpression of hsa-let-7a-5p in human retinal microvascular endothelial cells (HRMECs) significantly promoted proliferation rates of HRMECs. In conclusion, the three-miRNA signature from serum may serve as a noninvasive diagnostic biomarker for DR. Furthermore, we showed that DR-associated miRNAs may be involved in the pathogenesis of DR, at least in part, through modifying proliferation of HRMECs.

The intrinsic optical bistability of the nonlinear composite consisting of coated cylinders with nonlinear core and graded Drude shell is investigated with self-consistent mean-field approximation. We derive the nonlinear equation of near field for such graded composite in the quasistatic limit. We demonstrate that the bistability threshold and the bistable width are highly dependent on the core radius, the incident frequency, and the graded coefficient of the coated cylinder inclusion. It is found that the optical bistability appears only when the core radius and the incident frequency satisfy some specific conditions. Therefore, the optical bistability for nonlinear composite materials may be optimized by the suitable adjustment of the physical and geometrical parameters. Our results may be helpful for the design of the nonlinear device with appropriate bistability.