Sensing light without forming images In the rodent retina, intrinsically photosensitive retinal ganglion cells (ipRGCs) entrain circadian rhythms, modulate mood, and signal pupillary accommodation. Such responses are light-driven but not image-based. Working with donated human organ tissues, Mure et al. used electrophysiological approaches to identify ipRGCs in retina. The retina has more cones than retinas of nocturnal mice rats. Differences sensitivity, latency, duration identified three...

Significance This study resolves a long-standing question about the ability of humans to perceive near infrared radiation (IR) and identifies mechanism driving human IR vision. A few previous reports our expanded psychophysical studies here reveal that can detect at wavelengths longer than 1,000 nm it as visible light, finding has not received satisfactory physical explanation. We show light activates photoreceptors through nonlinear optical process. also caused photoisomerization purified...

Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon considered maladaptive and may preclude vision restoration blind. However, several recent studies utilizing triggered ablation have shown adaptive responses bipolar cells expected support normal vision. Whether such homeostatic occurs during progressive degenerative disease help maintain visual behavior is unknown. We addressed issue an established mouse model...

Photoreceptor cell death is the proximal cause of blindness in many retinal degenerative disorders; hence, understanding gene regulatory networks that promote photoreceptor survival at forefront efforts to combat blindness. Down-regulation microRNA (miRNA)-processing enzyme DICER1 pigmented epithelium has been implicated geographic atrophy, an advanced form age-related macular degeneration (AMD). However, little known about function mature rod cells, another type severely affected AMD. Using...

Mutations that affect calcium homeostasis (Ca2+) in rod photoreceptors are linked to retinal degeneration and visual disorders such as retinitis pigmentosa congenital stationary night blindness (CSNB). It is thought the concentration of Ca2+ outer segments controlled by a dynamic balance between influx via cGMP-gated (CNG) channels extrusion Na+/Ca2+, K+ exchangers (NCKX1). The extrusion-driven lowering [Ca2+]i following light exposure controls their adaptation response termination. Mutant...

Calcium (Ca

An In vivo electroretinogram (ERG) signal is composed of several overlapping components originating from different retinal cell types, as well noise extra-retinal sources. Ex ERG provides an efficient method to dissect the function cells directly intact isolated retina animals or donor eyes. addition, ex can be used test efficacy and safety potential therapeutic agents on tissue humans. We show here how commercially available in systems conduct recordings mouse retinas. combine light...

Cones comprise only a small portion of the photoreceptors in mammalian retinas. However, cones are vital for color vision and visual perception, their loss severely diminishes quality life patients with retinal degenerative diseases. function bright light have higher demand energy than rods; yet, mechanisms that support requirements poorly understood. One such pathway potentially could sustain under basal stress conditions is macroautophagy. We addressed role macroautophagy by examining how...

Photoreceptors are specialized neurons that rely on Ca2+ to regulate phototransduction and neurotransmission. Photoreceptor dysfunction degeneration occur when intracellular homeostasis is disrupted. maintained partly by mitochondrial uptake through the uniporter (MCU), which can influence cytosolic signals, stimulate energy production, trigger apoptosis. Here we discovered zebrafish cone photoreceptors express unusually low levels of MCU. We expected this would be important prevent overload...

Aims/Purpose: Photoreceptor death triggers retinal rewiring and remodeling that are generally thought to be detrimental for vision. Some recent research results challenge this dogma. It was recently shown in early‐stage retinitis pigmentosa (RP), the retina compensates reduced rod population activity by upscaling synaptic transmission between remaining rods bipolar cells. The purpose of current project is study molecular mechanism behind phenomenon. Methods: To model primary pathology, P23H...

Aims: The isolated mouse and postmortem human retina can serve as a sensitive biosensor for preclinical drug testing. To facilitate testing with minimal amounts of potential molecules or nanostructures, we developed closed‐perfusion tERG setup. major challenge small perfusate volumes was the healthiness stability in prolonged experiments. Methods: We conducted ex vivo experiments using WT C57BL/6J Gnat1‐/‐ mouse, donor retinas (Lion's Eye Bank, Utah). punches were embedded specimen holder...

Aims/Purpose: Photoreceptor death triggers retinal rewiring and remodeling that are generally thought to be detrimental for vision. Some recent research results challenge this dogma. It was recently shown in early‐stage retinitis pigmentosa (RP), the retina compensates reduced rod population activity by upscaling synaptic transmission between remaining rods bipolar cells. The purpose of current project is study molecular mechanism behind phenomenon. Methods: To model primary pathology, P23H...

Aims: The isolated mouse and postmortem human retina can serve as a sensitive biosensor for preclinical drug testing. To facilitate testing with minimal amounts of potential molecules or nanostructures, we developed closed‐perfusion tERG setup. major challenge small perfusate volumes was the healthiness stability in prolonged experiments. Methods: We conducted ex vivo experiments using WT C57BL/6J Gnat1‐/‐ mouse, donor retinas (Lion's Eye Bank, Utah). punches were embedded specimen holder...

Abstract Rods and cones use intracellular Ca 2+ to regulate many functions, including phototransduction neurotransmission. The Mitochondrial Calcium Uniporter (MCU) complex is thought be the primary pathway for entry into mitochondria in eukaryotes. We investigate hypothesis that mitochondrial uptake via MCU influences energy metabolism photoreceptors using a mcu -/- zebrafish rod photoreceptor-specific Mcu mouse. Using genetically encoded sensors directly examine cone mitochondria, we found...

Calcium ions (Ca(2+)) modulate the phototransduction cascade of vertebrate cone photoreceptors to tune gain, inactivation, and light adaptation. In darkness, continuous current entering outer segment through cGMP-gated (CNG) channels is carried in part by Ca(2+), which then extruded back extracellular space. The mechanism Ca(2+) extrusion from mammalian cones not understood. dominant view has been that cone-specific isoform Na(+)/Ca(2+), K(+) exchanger, NCKX2, responsible for removing their...

The leading edge of the a-wave ERG is generally believed to accurately reflect changes in circulating current through cGMP-gated channels outer segment plasma membrane rods and cones. aspartate-isolated mammalian electroretinogram (ERG) a rod-saturating flash contains fast "nose"-like wave temporally overlapping with a-wave. We characterize nature this nose, investigate mechanisms involved nose mechanism, propose model that can explain generation component rod inner segment. On basis...

The cone-driven flash responses of mouse electroretinogram (ERG) increase as much twofold over the course several minutes during adaptation to a rod-compressing background light. origins this phenomenon were investigated in present work by recording preflash-isolated (M-)cone ex vivo darkness and application various steady lights. In protocol, cone stimulating was preceded preflash that maintains rods under saturation (hyperpolarized) allow selective stimulation cones at varying light...

Determine the impact of rod photoreceptor-specific expression Cre recombinase on kinetics phototransduction in mouse eye and identify changes gene that underlie any observed phenotypic differences.Transretinal ERG single-cell suction electrode recordings were used to measure a line exhibiting expression, results compared with those from control non-Cre-expressing littermates. Gene evaluated using RNA sequencing transcriptome analysis. The pattern Rgs9bp was determined by mapping reads genome...

Light adaptation of photoreceptor cells is mediated by Ca2+-dependent mechanisms. In darkness, Ca2+ influx through cGMP-gated channels into the outer segment photoreceptors balanced extrusion via Na+/Ca2+, K+ exchangers (NCKXs). activates a G protein signaling cascade, which closes and decreases levels in because continuing NCKXs. Guanylate cyclase-activating proteins (GCAPs) then up-regulate cGMP synthesis activating retinal membrane guanylate cyclases (RetGCs) low This activation RetGC...

Background The rate-limiting step that determines the dominant time constant (τD) of mammalian rod photoresponse recovery is deactivation active phosphodiesterase (PDE6). Physiologically relevant Ca2+-dependent mechanisms would affect PDE inactivation have not been identified. However, recently it has shown τD modulated by background light in mouse rods. Methodology/Principal Findings We used ex vivo ERG technique to record pharmacologically isolated photoreceptor responses (fast PIII...