Optogenetics, a powerful biotechnology that uses light to regulate biological processes with precision and high spatiotemporal resolution, has significantly advanced research across diverse fields. Our laboratory has been dedicated to expanding the frontiers of optogenetics in two primary areas: unraveling fundamental cellular mechanisms and developing new therapeutic approaches. (1) Addressing a long-standing methodological challenge in cell biology, we have engineered light-gated mechanostimulators, which, for the first time, can apply mechanical forces directly to intracellular organelles. Despite extensive research on the roles of the plasma membrane and cytoskeleton in cellular mechanosensing and mechanotransduction, we found that intracellular organelles, including the ER and mitochondria, are also capable of sensing and responding to mechanical forces, thereby presenting them as novel players in the map of mechanotransduction. (2) To explore the therapeutic possibilities of optogenetics, we have devised methods to control TrkB signaling optically — a pathway essential for cell survival, growth, and proliferation. Our research has demonstrated that activating TrkB signaling with light can protect Retinal ganglion cells (RGCs) — the neurons that relay visual information from the eye to the brain — in mouse models of ocular diseases, thus opening new avenues for optogenetics-based neuroprotective treatments for RGC-related injuries and diseases.