Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo.

Retinal ganglion cell (RGC) degeneration drives vision loss in blinding conditions. RGC death is often triggered by axon degeneration in the optic nerve. Here, we study the contributions of dynamic and homeostatic Ca2+ levels to RGC death from axon injury. We find that axonal Ca2+ elevations from optic nerve injury do not propagate over distance or reach RGC somas, and acute and chronic Ca2+ dynamics do not affect RGC survival. Instead, we discover that baseline Ca2+ levels vary widely between RGCs and predict their survival after axon injury, and that lowering these levels reduces RGC survival. Further, we find that well-surviving RGC types have higher baseline Ca2+ levels than poorly surviving types. Finally, we observe considerable variation in the baseline Ca2+ levels of different RGCs of the same type, which are predictive of within-type differences in survival.

Transpupillary Two-photon In vivo Imaging of the Mouse Retina.

The retina transforms light signals from the environment into electrical signals that are propagated to the brain. Diseases of the retina are prevalent and cause visual impairment and blindness. Understanding how such diseases progress is critical to formulating new treatments. In vivo microscopy in animal models of disease is a powerful tool for understanding neurodegeneration and has led to important progress towards treatments of conditions ranging from Alzheimer's disease to stroke. Given that the retina is the only central nervous system structure inherently accessible by optical approaches, it naturally lends itself towards in vivo imaging. However, the native optics of the lens and cornea present some challenges for effective imaging access. This protocol outlines methods for in vivo two-photon imaging of cellular cohorts and structures in the mouse retina at cellular resolution, applicable for both acute- and chronic-duration imaging experiments. It presents examples of retinal ganglion cell (RGC), amacrine cell, microglial, and vascular imaging using a suite of labeling techniques including adeno-associated virus (AAV) vectors, transgenic mice, and inorganic dyes. Importantly, these techniques extend to all cell types of the retina, and suggested methods for accessing other cellular populations of interest are described. Also detailed are example strategies for manual image postprocessing for display and quantification. These techniques are directly applicable to studies of retinal function in health and disease.

Macrophage Plasticity and Function in the Eye and Heart.

Macrophages are important mediators of inflammation and tissue remodeling. Recent insights into the heterogeneity of macrophage subpopulations have renewed interest in their functional diversity in homeostasis and disease. In addition, their plasticity enables them to perform a variety of functions in response to changing tissue contexts, such as those imposed by aging. These qualities make macrophages particularly intriguing cells given their dichotomous role in protecting against, or accelerating, diseases of the cardiovascular system and the eye, two tissues that are particularly susceptible to the effects of aging. We review novel perspectives on macrophage biology, as informed by recent studies detailing the diversity of macrophage identity and function, as well as mechanisms influencing macrophage behavior that might offer opportunities for new therapeutic strategies.

Real-Time Gas Mixture Analysis Using Mid-Infrared Membrane Microcavities.

Real-time gas analysis on-a-chip was demonstrated using a mid-infrared (mid-IR) microcavity. Optical apertures for the microcavity were made of ultrathin silicate membranes embedded in a silicon chip using the complementary metal-oxide-semiconductor (CMOS) process. Fourier transform infrared spectroscopy (FTIR) shows that the silicate membrane is transparent in the range of 2.5-6.0 µm, a region that overlaps with multiple characteristic gas absorption lines and therefore enables gas detection applications. A test station integrating a mid-IR tunable laser, a microgas delivery system, and a mid-IR camera was assembled to evaluate the gas detection performance. CH4, CO2, and N2O were selected as analytes due to their strong absorption bands at λ = 3.25-3.50, 4.20-4.35, and 4.40-4.65 µm, which correspond to C-H, C-O, and O-N stretching, respectively. A short subsecond response time and high gas identification accuracy were achieved. Therefore, our chip-scale mid-IR sensor provides a new platform for an in situ, remote, and embedded gas monitoring system.

BioPad: Leveraging off-the-Shelf Video Games for Stress Self-Regulation.

This paper presents an approach to use commercial videogames for biofeedback training. It consists of intercepting signals from the game controller and adapting them in real-time based on physiological measurements from the player. We present three sample implementations and a case study for teaching stress self-regulation via an immersive car racing game. We use a crossover gaming device to manipulate controller signals, and a respiratory sensor to monitor the players' breathing rate. We then alter the speed of the car to encourage slow deep breathing, in this way, allowing players to reduce their arousal while playing the game. We evaluate the approach against an alternative form of biofeedback that uses a graphic overlay to convey physiological information, and a control condition (playing the game without biofeedback). Experimental results show that our approach can promote deep breathing during gameplay, and also during a subsequent task, once biofeedback is removed. Our results also indicate that delivering biofeedback through subtle changes in gameplay can be as effective as delivering them directly through a visual display. These results open the possibility to develop low-cost and engaging biofeedback interventions using a variety of commercial videogames to promote adherence.

Advancements in Induced Pluripotent Stem Cell Technology for Cardiac Regenerative Medicine.

Cardiovascular diseases remain the leading causes of morbidity and mortality in the developed world. Cellular-based cardiac regenerative therapy serves as a potential approach to treating cardiovascular diseases. Although various cellular types have been tested, induced pluripotent stem cells (iPSCs) are regarded as a promising cell source for therapy. In this review, we will highlight some of the advances in generating iPSCs and differentiation to cardiac cells. We will also discuss the progress in modeling cardiovascular diseases using iPSCs-derived cardiac cells. As we continue to make progress in iPSC and cardiac differentiation technology, we will come closer to the application of cardiac regenerative medicine.