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.

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.

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.

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.