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Background Insulin positively correlates with the length of the eye axis and is increased in the vitreous and serum of patients with pathological myopia (PM). How insulin influences the physiological process of retinal pigment epithelial (RPE) cells in PM remains unclear. This study aimed to explore the effect of insulin on the ultrastructure and function of RPE cells and the role of PI3K/AKT/mTOR signaling involved in the development of PM. Methods The ARPE-19 cells were treated with different concentrations of insulin to analyze the cell morphology, cell viability, the protein level of insulin receptor β, and the mRNA and protein levels of and PM-related factors (TIMP-2, MMP-2, bFGF, and IGF-1). The ultrastructure of APRE-19 cells was also observed after insulin treatment. Besides, the PI3K/AKT/mTOR signaling was studied with or without the PI3K inhibitor LY294002 in ARPE-19 cells. Results Insulin enhanced the cell viability of ARPE-19 cells and caused the endoplasmic reticulum to expand and vesiculate, suggesting increased secretion of growth factors and degeneration in ARPE-19 cells. Furthermore, the insulin receptor β was stimulated with insulin treatment, subsequently, the phosphorylation of AKT and mTOR was positively activated, which was adversely suppressed in the presence of LY294002. The secretion of TIMP-2 and bFGF was significantly decreased, and the secretion of MMP-2 and IGF-1 was highly elevated with insulin treatment depending on the concentration in ARPE-19 cells. Furthermore, the effect of insulin on PM-related proteins was restored with the addition of LY294002. Conclusions Our results indicated that insulin regulated the secretion of PM-related factors via the PI3K/AKT/mTOR signaling pathway in retinal pigment epithelial cells, and thus probably promoted the development of PM through transducing regulation signals from retina to choroid and sclera.

Aim The aims of this study are to investigate the relative regulation between miR-126 and VEGF/PI3K/AKT signaling pathway in retinal vascular endothelial cells. Methods Rhesus macaque choroid-retinal endothelial cell line (RF/6A) cells were cultured in high glucose to imitate the conditions occurring in DR. First, we detected the expression of miR-126, VEGFA and PIK3R2 in RF/6A cells on the condition of high glucose by q-PCR and western blot. Then, after addition of miR-126 mimics and miR-126 inhibitor, we investigated the function of miR-126 in RF/6A cells by scratch wound, Transwell migration and tube formation assays, and the effect of miR-126 on the expression of VEGFA, PIK3R2 and AKT. Moreover, bioinformatics analysis and luciferase array were used to confirm the direct or specific regulation of miR-126 to VEGFA or PIK3R2. Results Here, first, we found that high glucose could induce the decrease of miR-126 and the increase of VEGFA and PIK3R2 in RF/6A. Then, by scratch wound, Transwell migration and tube formation assays, we found that miR-126 overexpression could inhibit the migration and sprouting of RF/6A cells induced by high glucose, while knockdown of miR-126 led to the opposite results. Moreover, overexpression of miR-126 inhibited the increased expression of VEGFA, PIK3R2, SDF-1α, VCAM-1, and SPRED1, and the activation of AKT1 induced by high glucose and miR-126 inhibitor caused the opposite results which were determined by q-PCR and western blot. In addition, by luciferase assay, we found that miR-126 could directly negatively regulate VEGFA and PIK3R2. Conclusion Our results suggest that miR-126 overexpression inhibits the migration and sprouting of RF/6A cells induced by high glucose which might possibly be by blocking VEGFA and PIK3R2 in the VEGF/PI3K/AKT signaling pathway.

A new method for the detection of signals in "noise", which is based on the premise that the "noise" is chaotic with at least one positive Lyapunov exponent, is presented. The method is naturally rooted in nonlinear dynamical systems, and relies on neural networks for its implementation. We first present a theoretical basis for methods of modeling the underlying dynamics of a chaotic system using a time series. The subject matter selected for this part of the thesis is written with emphasis on experimental studies of chaos. Specifically, we discuss the issues involved in the reconstruction of chaotic dynamics, attractor dimensions, and Lyapunov exponents. We describe procedures for the estimation of the correlation dimension and the Lyapunov exponents. The method of false nearest neighbors analysis fur finding the minimum embedding dimension is described. The need for an adequate data length is stressed. In the second part of the thesis we apply the chaos-based method to the radar detection of a small target in sea clutter. To justify the applicability of the new method to this problem, we clearly need to show in a convincing way that sea clutter is indeed the result of a chaotic dynamical system. We do this by presenting the results of a detailed experimental study using surface-truthed real-life data collected by means of an instrument quality radar at different geographic locations. Specifically, we show that (1) sea clutter has a finite correlation dimension, (2) the largest Lyapunov exponent of sea clutter is positive, and (3) sea clutter is locally predictable. Most importantly, we show that both the correlation dimension and the largest Lyapunov exponent are essentially invariant to the choice of radar signal component used to construct the time series, and that the correlation dimension and Lyapunov exponent do not appear to change appreciably with sea state or with geographic locations. These results suggest that there may exist universal chaotic structure responsible for the generation of sea clutter. Perhaps the most dramatic result presented in the thesis is the fact that this prior information (i.e., the knowledge that sea clutter exhibits chaotic behavior) can be exploited to build a chaos-based detettor operating on amplitude information only (as in a noncoherent marine radar), realizing a performance comparable to that of a "conventional" receiver using coherent radar data (i.e., both amplitude and phase). This result points to the potential of trading off sophisticated but inexpensive computer software for expensive microwave hardware. Lastly, we show experimentally that a chaos-based coherent detector can provide a further improvement in radar detection performance. Doctor of Philosophy (PhD)