A5043951043- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Retinal Diseases and Treatments
- Receptor Mechanisms and Signaling
- Photochromic and Fluorescence Chemistry
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Retinoids in leukemia and cellular processes
- bioluminescence and chemiluminescence research
- Circadian rhythm and melatonin
- Neuroscience and Neural Engineering
- Advanced Fluorescence Microscopy Techniques
- Visual perception and processing mechanisms
- Olfactory and Sensory Function Studies
- Ocular and Laser Science Research
- Connexins and lens biology
- Glaucoma and retinal disorders
- Retinal and Optic Conditions
- Ocular Diseases and Behçet’s Syndrome
- Retinal Imaging and Analysis
- Cellular transport and secretion
- melanin and skin pigmentation
- Protein Kinase Regulation and GTPase Signaling
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
University of California, Irvine
2021-2025
University of California, Los Angeles
2023
Southern California University for Professional Studies
2023
University of Southern California
2023
University of California System
2023
Washington University in St. Louis
2011-2021
Indiana University School of Medicine
2015
University of Missouri–St. Louis
2015
University of Washington
2010-2012
Johns Hopkins University
2003-2008
Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor-mediated vision loss patients. It is not known how CRALBP supports function or altered leads dysfunction. Here, we determined that deletion of Rlbp1 mice impairs retinal visual cycle. Mice lacking exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven behavior light responses. Additionally, dark adaptation was largely suppressed CRALBP-deficient animals....
Retinal rod photoreceptor cells have double membrane discs located in their outer segments (ROS) that are continuously formed proximally from connecting cilia (CC) and phagocytized distally by the retinal pigmented epithelium. The major component of these discs, light-sensitive visual pigment rhodopsin (Rho), consists an opsin protein linked to 11-cis-retinal. P23H mutation (P23H opsin) is most common cause human blinding autosomal dominant retinitis pigmentosa (adRP). A mouse model adRP...
Thyroid hormone (TH) signaling plays an important role in the regulation of long-wavelength vision vertebrates. In retina, thyroid receptor β ( thrb ) is required for expression long-wavelength-sensitive opsin lws red cone photoreceptors, while retinal pigment epithelium (RPE), TH regulates a cytochrome P450 enzyme, cyp27c1 , that converts vitamin A 1 into 2 to produce red-shifted chromophore. To better understand how controls these processes, we analyzed phenotype zebrafish with mutations...
Vision is initiated by the reception of light photoreceptors and subsequent processing via downstream retinal neurons. Proper circuit organization depends on multifunctional tissue polarity protein FAT3, which required for amacrine cell connectivity lamination. Here, we investigated function Fat3 mutant mice found decreases in both electroretinography perceptual responses to high-frequency flashes. These defects did not correlate with abnormal wiring, pointing instead a role bipolar subtypes...
Even in healthy individuals, aging leads to deterioration visual acuity, contrast sensitivity, field, and dark adaptation. Little is known about the neural mechanisms that drive age-related changes of retina and, more specifically, photoreceptors. According one hypothesis, rod function due limited availability 11- cis -retinal for pigment formation. To determine how affects photoreceptors test retinoid-deficiency we compared morphological functional properties rods adult aged B6D2F1/J mice....
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...
Mutations in the ABCA4 gene are a common cause of autosomal recessive retinal degeneration. All mouse models to date based on knockouts Abca4, even though disease is often caused by missense mutations such as complex allele L541P;A1038V (PV). We now show that PV mutation causes severe human whereas V alone mild disease. Mutant proteins expressed heterologously mammalian cells retained normal cellular localization. However, basal and all-trans-retinal-stimulated ATPase activities were reduced...
A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa one the most common degenerative diseases eye and associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown determinant Nrl, could make cells resistant effects mutations rod-specific genes, thereby preventing loss. To test this idea, we engineered tamoxifen-inducible allele Nrl...
In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical cycle. This shortfall is compensated, in part, retinal G-protein-coupled receptor (RGR) photoisomerase, which expressed both pigment epithelium (RPE) and Müller cells. The relative contributions of these two cellular pools RGR to maintenance photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach elucidate kinetics RGR-mediated recovery following exposure....
Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies mitigate pathophysiology regardless of the underlying genetic lesion desirable due to diversity mutations found such diseases. We tested a systems pharmacology-based strategy suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, bromocriptine coadministration. The improves cone photoreceptor function...
Retinitis pigmentosa 1 (RP1) is a common inherited retinopathy with variable onset and severity. The RP1 gene encodes photoreceptor-specific, microtubule-associated ciliary protein containing the doublecortin (DCX) domain. Here we show that another photoreceptor-specific Rp1-like (Rp1L1) in mice also localized to axoneme of outer segments (OSs) connecting cilia rod photoreceptors, overlapping Rp1. Rp1L1 −/− display scattered OS disorganization, reduced electroretinogram amplitudes,...
A negative phototransduction feedback in rods and cones is critical for the timely termination of their light responses extending function to a wide range intensities. The calcium mechanisms that modulate have been studied extensively. However, corresponding modulation enable terminate rapidly adapt bright light, properties our daytime vision, are still not understood. In cones, guanylyl cyclase potentially key step modulation. activity modulated by calcium-binding activating proteins (GCAP1...
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...
Delivering therapeutics to the posterior segment of eye is challenging due various anatomical and physical barriers. While significant improvements have been realized by introducing direct injections diseased sites, these approaches come with potential side effects that can range from simple inflammation severe retinal damage. The topical instillation drugs remains a safer preferred alternative for patients' compliance. Here, we report synthesis penetratin-complexed, redox-responsive...