A5042351327- Retinal Development and Disorders
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Adenosine and Purinergic Signaling
- Neuroscience and Neural Engineering
- Ion channel regulation and function
- Neuroscience of respiration and sleep
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Diseases and Treatments
- Amino Acid Enzymes and Metabolism
- Glaucoma and retinal disorders
- Circadian rhythm and melatonin
- Neurological Complications and Syndromes
- Sleep and Wakefulness Research
- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Cardiac electrophysiology and arrhythmias
- Nuclear Receptors and Signaling
- Neurological Disorders and Treatments
- Tryptophan and brain disorders
- Genetic Syndromes and Imprinting
- Nitric Oxide and Endothelin Effects
- Autoimmune Neurological Disorders and Treatments
- Retinal and Optic Conditions
University of California, Berkeley
2017-2024
Oregon Health & Science University
2011-2023
University of California System
2023
American Academy of Optometry
2018
The University of Melbourne
2003-2009
Ophthalmology Associates (United States)
2009
Australian College of Optometry
2003
In the primate visual system, ganglion cells of magnocellular pathway underlie motion and flicker detection are relatively transient, while more sustained parvocellular have comparatively lower temporal resolution, but encode higher spatial frequencies. Although it is presumed that functional differences in bipolar contribute to tuning two pathways, properties relevant not yet been examined detail. Here, by making patch-clamp recordings acute slices macaque retina, we show within pathway,...
α<sub>2</sub>δ-4 is an auxiliary subunit of voltage-gated Ca<sub>v</sub>1.4 L-type channels that regulate the development and mature exocytotic function photoreceptor ribbon synapse. In humans, mutations in <i>CACNA2D4</i> gene encoding cause heterogeneous forms vision impairment underlying pathogenic mechanisms which remain unclear. To investigate retinal α<sub>2</sub>δ-4, we used genome editing to generate knock-out (α<sub>2</sub>δ-4 KO) mouse. male female KO mice, rod spherules lack...
Abstract To maintain a stable and clear image of the world, our eyes reflexively follow direction in which visual scene is moving. Such gaze-stabilization mechanisms reduce blur as we move environment. In non-primate mammals, this behaviour initiated by retinal output neurons called ON-type direction-selective ganglion cells (ON-DSGCs), detect motion transmit signals to brainstem nuclei that drive compensatory eye movements 1 . However, ON-DSGCs have not yet been identified retina primates,...
Abstract Photoreceptor degenerations can trigger morphological alterations in second‐order neurons, however, the functional implications of such changes are not well known. We conducted a longitudinal study, using whole‐cell patch‐clamp, immunohistochemistry and electron microscopy to correlate physiological with anatomical bipolar cells rd10 mouse – model autosomal recessive retinitis pigmentosa. Rod (RBCs) showed progressive mGluR6‐induced currents advancing rod photoreceptor degeneration....
We have previously demonstrated that photoreceptors express P2X7 purinoceptors. These excitatory receptors are activated by extracellular adenosine 5′-triphosphate (ATP) and been implicated in neurodegeneration other parts of the central nervous system (CNS). In this study we examined whether ATP could contribute to photoreceptor degeneration rodents through excessive activation P2 Intravitreal injection high concentrations into normal rat eyes induced extensive selective apoptosis within 18...
Secretagogin, a recently cloned member of the EF-hand family calcium binding proteins, was localized in mouse, rat, and rabbit retina using immunofluorescence immunohistochemistry. Secretagogin is expressed subpopulations ON OFF cone bipolar cells; however, no immunoreactivity observed rod cells any these species. Using subtype-specific markers mice expressing green fluorescent protein (GFP) within specific cell classes, we found that secretagogin Types 2, 3, 4, 5, 6 possibly Type 8 mouse...
Visual signals are segregated into parallel pathways at the first synapse in retina between cones and bipolar cells. Within OFF of mammals, selective expression AMPA or kainate-type glutamate receptors dendrites different OFF-bipolar cell types is thought to contribute formation distinct temporal channels. receptors, with rapid recovery from desensitization, proposed transmit high frequency signals, whereas kainate (KARs) presumed encode lower frequencies. Here we studied expressed by cells...
Abstract The distribution of P2X 7 receptor (P2X R) subunits was studied in the rat retina using a subunit‐specific antiserum. Punctate immunofluorescence observed inner and outer plexiform layers. Double labeling horizontal cell marker, calbindin, revealed extensive colocalization layer (OPL). Significant R kinesin, marker photoreceptor ribbons, also observed, indicating that this may be expressed at terminals. Furthermore, another band puncta identified below level terminals, adjacent to...
Silent voltage-gated potassium channel subunits (K V S) interact selectively with members of the K 2 family to modify their functional properties. The localization and roles these silent remain poorly understood. Mutations in S subunit, 8.2 ( KCNV2 ), lead severe visual impairment humans, but basis deficits remains unclear. Here, we examined localization, native interactions, properties 8.2-containing channels mouse, macaque, human photoreceptors either sex. In retina, colocalized 2.1 2.2...
Abstract Extracellular ATP mediates fast excitatory neurotransmission in many regions of the central nervous system through activation P2X receptors. Although several receptor subunits have been identified mammalian retina, little is known about functional role these receptors retinal signalling. The purpose present study was to investigate whether purinergic 7 are involved outer processing by assessing localization, degradation extracellular and effect on electroretinogram (ERG). Using...
Different types of retinal ganglion cells represent distinct spatiotemporal filters that respond selectively to specific features in the visual input. Much about circuitry and synaptic mechanisms underlie such specificity remains be determined. This study examines how N-methyl-d-aspartate (NMDA) receptor signaling combines with other excitatory inhibitory shape output small-field OFF brisk-sustained (OFF-BSGCs) rabbit retina. We used voltage clamp separately resolve NMDA,...
Detailed analysis of the synaptic inputs to primate DB1 bipolar cell has been precluded by absence a suitable immunohistochemical marker. Here we demonstrate that antibodies for EF-hand calcium-binding protein, secretagogin, strongly label as well mixed population GABAergic amacrine cells in macaque retina. Using secretagogin marker, show makes contact with both L/M S-cone photoreceptors and only minimal rod photoreceptors. Electron microscopy showed flat contacts at triad-associated...
Abstract Extracellular ATP is known to mediate fast, excitatory neurotransmission through activation of ionotropic P2X receptors. In this study, the localization 2 receptor (P2X R) subunit was studied in rat retina by using immunofluorescence immunohistochemistry and preembedding immunoelectron microscopy. The R observed large ganglion cells as well a subset amacrine cells. Double labeling revealed that 96% all R‐immunoreactive showed γ‐aminobutyric acid (GABA) immunoreactivity. Subsets...
Abstract The rate-limiting step in the recovery of photoreceptor light response is hydrolysis GTP by transducin, a reaction that accelerated RGS9–G β 5 complex, and its membrane anchor, R9AP. Similar complexes, including RGS7, RGS11, G 5, are found retinal ON-bipolar cell dendrites. Here, we present evidence R9AP also expressed dendritic tips cells. Immunofluorescent staining for revealed punctate pattern labeling outer plexiform layer, where it colocalized with mGluR6. In photoreceptors,...
Photoreceptor degeneration differentially impacts glutamatergic signaling in downstream On and Off bipolar cells. In rodent models, photoreceptor leads to loss of cells, whereas cells appear retain glutamate sensitivity, even after extensive loss. The localization identity the receptors that mediate these residual responses have not been determined. Recent studies show macaque mouse receive input primarily through kainate-type receptors. Here, we studied impact on receptor their associated...
All retina-based vision restoration approaches rely on the assumption that photoreceptor loss does not preclude reactivation of remaining retinal architecture. Whether extended periods limit efficacy restorative therapies at level is unknown. We examined long-term changes in optogenetic responsivity foveal ganglion cells (RGCs) non-human primates following localized ablation by high-intensity laser exposure. By performing fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO)...