500 W peak power cavity dumped 2 µm GaSb-based VECSEL.

A single transverse mode high-pulse-energy vertical-external-cavity surface-emitting laser (VECSEL) was developed. The GaSb-based VECSEL emits at a wavelength of 2.04 µm with a peak power exceeding 500 W while maintaining good beam quality.

Efficacy and Safety of Glycosidic Enzymes for Improved Gene Delivery to the Retina following Intravitreal Injection in Mice.

Viral gene delivery is showing great promise for treating retinal disease. Although subretinal vector delivery has mainly been used to date, intravitreal delivery has potential advantages if low retinal transduction efficiency can be overcome. To this end, we investigated the effects of co-injection of glycosaminoglycan-degrading enzymes, singly or in combination, with AAV2 as a method of increasing retinal transduction.

Generation of near-diffraction-limited, high-power supercontinuum from 1.57 μm to 12 μm with cascaded fluoride and chalcogenide fibers.

We generate a supercontinuum (SC) spectrum ranging from 1.57 μm to 12 μm (20 dB bandwidth) with a soft glass fiber cascade consisting of ---- fiber, fiber, and fiber pumped by a nanosecond thulium master oscillator power amplifier system. The highest on-time average power generated is 417 mW at 33% duty cycle.

Non-immunoglobulin scaffold proteins: Precision tools for studying protein-protein interactions in cancer.

Cancer is frequently characterised by dysregulation of the cellular signalling processes that govern proliferation, survival and attachment. Understanding such dysregulation continues to present a challenge given the importance of protein-protein interactions in intracellular processes. Exploring this protein-protein interactome requires novel tools capable of discriminating between highly homologous proteins, individual domains and post-translational modifications.

Mid-infrared supercontinuum generation from 1.6 to >11 μm using concatenated step-index fluoride and chalcogenide fibers.

We demonstrate an all-fiber supercontinuum source that generates a continuous spectrum from 1.6 μm to >11  μm with 417 mW on-time average power at 33% duty cycle. By utilizing a master oscillator power amplifier pump with three amplification stages and concatenating solid core ZBLAN, arsenic sulfide, and arsenic selenide fibers, we shift 1550 nm light to ∼4.

Rods progressively escape saturation to drive visual responses in daylight conditions.

Rod and cone photoreceptors support vision across large light intensity ranges. Rods, active under dim illumination, are thought to saturate at higher (photopic) irradiances. The extent of rod saturation is not well defined; some studies report rod activity well into the photopic range.

Meclofenamic acid improves the signal to noise ratio for visual responses produced by ectopic expression of human rod opsin.

Purpose: Retinal dystrophy through outer photoreceptor cell death affects 1 in 2,500 people worldwide with severe impairment of vision in advanced stages of the disease. Optogenetic strategies to restore visual function to animal models of retinal degeneration by introducing photopigments to neurons spared degeneration in the inner retina have been explored, with variable degrees of success. It has recently been shown that the non-steroidal anti-inflammatory and non-selective gap-junction blocker meclofenamic acid (MFA) can enhance the visual responses produced by an optogenetic actuator (channelrhodopsin) expressed in retinal ganglion cells (RGCs) in the degenerate retina.

Affimer proteins are versatile and renewable affinity reagents.

Molecular recognition reagents are key tools for understanding biological processes and are used universally by scientists to study protein expression, localisation and interactions. Antibodies remain the most widely used of such reagents and many show excellent performance, although some are poorly characterised or have stability or batch variability issues, supporting the use of alternative binding proteins as complementary reagents for many applications. Here we report on the use of Affimer proteins as research reagents.

Melanopsin Contributions to the Representation of Images in the Early Visual System.

Melanopsin photoreception enhances retinal responses to variations in ambient light (irradiance) and drives non-image-forming visual reflexes such as circadian entrainment [1-6]. Melanopsin signals also reach brain regions responsible for form vision [7-9], but melanopsin's contribution, if any, to encoding visual images remains unclear. We addressed this deficit using principles of receptor silent substitution to present images in which visibility for melanopsin versus rods+cones was independently modulated, and we recorded evoked responses in the mouse dorsal lateral geniculate nucleus (dLGN; thalamic relay for cortical vision).

Modulation of Fast Narrowband Oscillations in the Mouse Retina and dLGN According to Background Light Intensity.

Background light intensity (irradiance) substantially impacts the visual code in the early visual system at synaptic and single-neuron levels, but its influence on population activity is largely unexplored. We show that fast narrowband oscillations, an important feature of population activity, systematically increase in amplitude as a function of irradiance in both anesthetized and awake, freely moving mice and at the level of the retina and dorsal lateral geniculate nucleus (dLGN). Narrowband coherence increases with irradiance across large areas of the dLGN, but especially for neighboring units.

High peak power cavity dumping semiconductor lasers.

We report on the development of a nanosecond pulsed kW-class optically pumped InGaAs semiconductor laser emitting around 1020 nm, which is suitable for applications such as incoherent laser radar, nonlinear optics, and materials processing. Using an intracavity Pockels cell to cavity-dump VECSELs, we are able to access large pulse energies by storing energy in the optical cavity rather than in the gain medium. We demonstrate peak powers >1  kW and 3 μJ pulses, show the pulse length is equivalent to the photon round-trip time, and show that the wavelength can be tuned within the gain bandwidth of the semiconductor gain.

Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn.

Twice a day, at dawn and dusk, we experience gradual but very high amplitude changes in background light intensity (irradiance). Although we perceive the associated change in environmental brightness, the representation of such very slow alterations in irradiance by the early visual system has been little studied. Here, we addressed this deficit by recording electrophysiological activity in the mouse dorsal lateral geniculate nucleus under exposure to a simulated dawn.

Tunable type II intracavity difference frequency generation at 5.4 μm in a two chip vertical external cavity surface emitting laser.

We report on the generation and experimental demonstration of intracavity type II difference frequency generation in a two chip InGaAs/GaAs vertical external cavity surface emitting laser. The presented two chip cavity provides two orthogonally polarized, independently tunable, high-intensity lasing modes with emissions around 970 and 1170 nm. A silver thiogallate nonlinear crystal is inserted in the common collinear folded region of the cavity to generate output in the mid-IR spectral band.

Restoration of Vision with Ectopic Expression of Human Rod Opsin.

Many retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically expressed human rod opsin, driven by either a non-selective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice.

Melanopsin-based brightness discrimination in mice and humans.

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection, no aspect of visual discrimination has been shown to rely upon ipRGCs.

Gain coupling of class A semiconductor lasers.

We report on the development of a gain-coupled class A semiconductor laser for dual-wavelength generation via optical switching. A vertical external cavity surface emitting laser (VECSEL) structure is used, because it provides a flexible platform for high-power, high-brightness output in the near-IR and visible ranges. For the first time (to our knowledge), two VECSEL cavities sharing a common gain region are studied.

Multichip vertical-external-cavity surface-emitting lasers: a coherent power scaling scheme.

We propose an efficient coherent power scaling scheme, the multichip vertical-external-cavity surface-emitting laser (VECSEL), in which the waste heat generated in the active region is distributed on multi-VECSEL chips such that the pump level at the thermal rollover is significantly increased. The advantages of this laser are discussed, and the development and demonstration of a two-chip VECSEL operating around 970 nm with over 19 W of output power is presented.

Analysis of high-reflectivity metal-dielectric mirrors for edge-emitting lasers.

A metal-dielectric mirror is shown as a simple solution for high-reflectivity coatings on cleaved-facet edge-emitting lasers, as well as a means to provide wavelength stabilization and spectral filtering. We show, through the use of a simple SiO2/Ti/Au coating, reflectivities better than 90% and a 25% reduction in the 30-dB linewidth of the output spectrum. Wavelength filtering and varying reflectivities are described as the result of multiple reflections and a coupled-cavity effect.