Edward N Pugh, Jr.

Edward N Pugh, Jr.
University of California, Davis | UCD · Department of Cell Biology and Human Anatomy; Department of Physiology & Membrane Biology

Doctor of Philosophy

About

241
Publications
33,818
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
16,519
Citations
Citations since 2017
39 Research Items
3978 Citations
20172018201920202021202220230200400600
20172018201920202021202220230200400600
20172018201920202021202220230200400600
20172018201920202021202220230200400600
Introduction
Phototransduction in rod and cone photoreceptors in vivo Functional and structural imaging of photoreceptors in vivo For nearly complete list of publications, cf Google Scholar Profile: https://scholar.google.com/citations?user=NAvEOK8AAAAJ&hl=en
Additional affiliations
June 2009 - April 2020
University of California, Davis
Position
  • Professor

Publications

Publications (241)
Article
Full-text available
Melanosomes, lipofuscin, and melanolipofuscin are the three principal types of pigmented granules found in retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we...
Preprint
Full-text available
Melanosomes, lipofuscin, and melanolipofuscin are the three principal types of granular pigmented organelles found in the retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin granules in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degener...
Article
Full-text available
Vertebrate retinal photoreceptors signal light by suppressing a circulating “dark current” that maintains their relative depolarization in the dark. This dark current is composed of an inward current through CNG channels and NCKX transporters in the outer segment that is balanced by outward current exiting principally from the inner segment. It has...
Article
Full-text available
RESULTS. The 3-dimensional multicolor confocal images provided a detailed visualization of the RPE cell mosaic, including its melanosomes and lipofuscin granules, and their varying characteristics in the different mice strains. The autofluorescence spectra, spatial distribution, and morphologic features of melanosomes and lipofuscin granules were m...
Article
Full-text available
Purpose: To investigate diurnal variation in the length of mouse rod outer segments in vivo. Methods: The lengths of rod inner and outer segments (RIS, ROS) of dark-adapted albino mice maintained on a 12-hour dark:12-hour light cycle with light onset 7 AM were measured at prescribed times (6:30 AM, 11 AM, 3:30 PM) during the diurnal cycle with o...
Article
Full-text available
It has been recently demonstrated that structures corresponding to the cell bodies of highly transparent cells in the retinal ganglion cell layer could be visualized noninvasively in the living human eye by optical coherence tomography (OCT) via temporal averaging. Inspired by this development, we explored the application of volumetric temporal ave...
Article
Full-text available
Significance Microglia, the resident macrophages of the central nervous system, are critical for synaptic pruning and maintenance and for mitigating injury and neurodegeneration. Determining whether microglia–neuron interactions are beneficial in specific instances has been difficult, largely because of the local and transient nature of the interac...
Article
Full-text available
Optical coherence tomography (OCT) is a powerful tool in ophthalmology that provides in vivo morphology of the retinal layers and their light scattering properties. The directional (angular) reflectivity of the retinal layers was investigated with focus on the scattering from retinal pigment epithelium (RPE). The directional scattering of the RPE w...
Article
Full-text available
Pugh highlights recent work ruling out a role for ultraweak photon emission in spontaneous photon-like events in retinal rods.
Article
Full-text available
Speckle is an inevitable consequence of the use of coherent light in imaging and acts as noise that corrupts image formation in most applications. Optical coherence tomographic imaging, as a technique employing coherence time gating, suffers from speckle. We present here a novel method of suppressing speckle noise intrinsically compatible with adap...
Article
Full-text available
In cancer research there is a fundamental need for animal models that allow the in vivo longitudinal visualization and quantification of tumor development, nanotherapeutic delivery, the tumor microenvironment including blood vessels, macrophages, fibroblasts, immune cells, and extracellular matrix, and the tissue response to treatment. To address t...
Preprint
Full-text available
Speckle is an inevitable consequence of the use of coherent light in optical coherence tomography (OCT), and often acts as noise that obscures micro-structures of biological tissue. We here present a novel method of suppressing speckle noise intrinsically compatible with adaptive optics (AO) in OCT system: by modulating the phase inside the imaging...
Presentation
Full-text available
To present our in vivo observations on angular dependence of mouse retina layers reflectivity measured by directional mouse retinal OCT system. To quantify and model differences observed between angular dependent reflectivity in inner and outer retina layers in different mouse strains.
Presentation
To evaluate feasibility of in vivo retinal imaging methods for monitoring of Photoreceptor-RPE-Choroid Neurovascular Unit (PRC-NVU) morphology and function locally and longitudinally in individual animals during aging.
Article
Full-text available
Vertebrate rod photoreceptors evolved the astonishing ability to respond reliably to single photons. In parallel, the proximate neurons of the visual system evolved the ability to reliably encode information from a few single-photon responses (SPRs) as arising from the presence of an object of interest in the visual environment. These amazing capab...
Article
Full-text available
Rods and cones mediate visual perception over 9 log units of light intensities, with both photoreceptor types contributing to a middle 3-log unit range that comprises most night-time conditions. Rod function in this mesopic range has been difficult to isolate and study in vivo because of the paucity of mutants that abolish cone signaling without ca...
Article
Full-text available
For in vivo mouse retinal imaging, especially with Adaptive Optics instruments, application of a contact lens is desirable, as it allows maintenance of cornea hydration and helps to prevent cataract formation during lengthy imaging sessions. However, since the refractive elements of the eye (cornea and lens) serve as the objective for most in vivo...
Article
Full-text available
Purpose To examine outer retinal band changes after flash stimulus and subsequent dark adaptation with ultrahigh-resolution optical coherence tomography (UHR-OCT). Methods Five dark-adapted left eyes of five normal subjects were imaged with 3-μm axial-resolution UHR-OCT during 30 minutes of dark adaptation following 96%, 54%, 23%, and 0% full-fiel...
Article
Full-text available
Background: Retinal detachment (RD) can lead to proliferative vitreoretinopathy (PVR), a leading cause of intractable vision loss. PVR is associated with a cytokine storm involving common proinflammatory molecules like IL6, but little is known about the source and downstream signaling of IL6 and the consequences for the retina. Here, we investigat...
Article
Full-text available
The temporal resolution of scotopic vision is thought to be constrained by the signaling kinetics of retinal rods, which use a highly amplified G-protein cascade to transduce absorbed photons into changes in membrane potential. Much is known about the biochemical mechanisms that determine the kinetics of rod responses ex vivo, but the rate-limiting...
Article
Full-text available
Significance Complete activation of the phototransduction G-protein cascade of dark-adapted rod photoreceptors causes outer segments to undergo 10% elongation and large local increases in backscattering, as measured in vivo with noninvasive, high-resolution optical coherence tomography. Maximal elongation is caused by a potentially harmful 20% incr...
Article
Optical Coherence Tomography (OCT) is a powerful clinical tool that measures near infrared light backscattered from the eye and other tissues. OCT is used for assessing changes in retinal structure, including layer thicknesses, detachments and the presence of drusen in patient populations. Our custom-built OCT system for the mouse eye quantitativel...
Article
We have successfully used the mouse eye as a non-surgical window for highly efficient, optical investigation of xenograft models, using a state-of-the-art ocular imaging facility, the UC Davis “EyePod”. The EyePod employs single-cell resolution intravital confocal microscopy and optical coherence tomography, performed completely non-invasively thro...
Article
Full-text available
Purpose: To quantify bleaching-induced changes in fundus reflectance in the mouse retina. Methods: Light reflected from the fundus of albino (Balb/c) and pigmented (C57Bl/6J) mice was measured with a multichannel scanning laser ophthalmoscopy optical coherence tomography (SLO-OCT) optical system. Serial scanning of small retinal regions was used...
Conference Paper
Full-text available
Chorioretinal blood vessel morphology in mice is of great interest to researchers studying eye disease mechanisms in animal models. Two leading retinal imaging modalities -- Optical Coherence Tomography (OCT) and Scanning Laser Ophthalmoscopy (SLO) -- have offered much insight into vascular morphology and blood flow. OCT “flow-contrast” methods hav...
Conference Paper
We present a novel system for adaptive optics two photon imaging. We utilize the bandwidth of the femtosecond excitation beam to perform coherence gated imaging (OCT) of the sample. The location of the focus is directly observable in the cross sectional OCT images, and adjusted to the desired depth plane. Next, using real time volumetric OCT, we pe...
Conference Paper
We present a new type of adaptive lens with 18 actuators that can correct up the 4th order of aberration. The Multi-actuator Adaptive Lens (M-AL) can guarantee a good level of aberration correction for many applications and, with respect to deformable mirror, it allows the realization of more compact and simple optical systems. The adaptive lens is...
Conference Paper
Full-text available
Scanning Laser Ophthalmoscopy (SLO) is a very important imaging tool in ophthalmology research. By combing with Adaptive Optics (AO) technique, AO-SLO can correct for ocular aberrations resulting in cellular level resolution, allowing longitudinal studies of single cells morphology in the living eyes. The numerical aperture (NA) sets the optical re...
Article
Full-text available
Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) provide complementary views of the retina, with the former collecting fluorescence data with good lateral but relatively low-axial resolution, and the latter collecting label-free backscattering data with comparable lateral but much higher axial resolution. To take maximal a...
Article
Full-text available
Scanning laser ophthalmoscopy (SLO) employs the eye's optics as a microscope objective for retinal imaging in vivo. The mouse retina has become an increasingly important object for investigation of ocular disease and physiology with optogenetic probes. SLO imaging of the mouse eye, in principle, can achieve submicron lateral resolution thanks to a...
Article
Full-text available
Vision begins in photoreceptor outer segments with light captured by opsins in continually synthesized disc membranes. The process by which rod photoreceptor discs are formed has been controversial. In this issue, Ding et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508093) show conclusively that rod discs are formed by plasma membrane...
Article
Full-text available
Adaptive optics is rapidly transforming microscopy and high-resolution ophthalmic imaging. The adaptive elements commonly used to control optical wavefronts are liquid crystal spatial light modulators and deformable mirrors. We introduce a novel Multi-actuator Adaptive Lens that can correct aberrations to high order, and which has the potential to...
Article
Full-text available
Adaptive optics scanning laser ophthalmoscopy (AO-SLO) has recently been used to achieve exquisite subcellular resolution imaging of the mouse retina. Wavefront sensing-based AO typically restricts the field of view to a few degrees of visual angle. As a consequence the relationship between AO-SLO data and larger scale retinal structures and cellul...
Article
Full-text available
A compact, non-invasive multi-modal system has been developed for in vivo mouse retina imaging. It is configured for simultaneously detecting green and red fluorescent protein signals with scanning laser ophthalmoscopy (SLO) back-scattered light from the SLO illumination beam, and depth information about different retinal layers by means of Optical...
Article
Full-text available
We present a novel adaptive lens that can correct high order aberrations, and which has the potential to increase the diffusion of adaptive optics to many new applications by simplifying the integration of a wavefront corrector inside existing systems. The adaptive lens design that we present can correct for Zernike wavefront aberrations up to the...
Article
Full-text available
Vertebrate vision begins when retinal photoreceptors transduce photons into electrical signals that are then relayed to other neurons in the eye, and ultimately to the brain. In rod photoreceptors, transduction of single photons is achieved by a well-understood G-protein cascade that modulates cGMP levels, and in turn, cGMP-sensitive inward current...
Article
Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal synthesis and cause Leber congenital amaurosis (LCA), a severe hereditary blindness occurring in early childhood. The pathology is attributed to a combination of 11-cis-retinal deficiency and photoreceptor degeneration. The mistrafficking of cone membrane-associate...
Article
Sustained vertebrate vision requires that opsin chromophores isomerized by light to the all-trans form be replaced with 11-cis retinal to regenerate the visual pigment. We have characterized the early receptor potential (ERP), a component of the electroretinogram arising from photoisomerization-induced charge displacements in plasma membrane visual...
Conference Paper
Full-text available
Optical coherence tomography is an imaging modality that is broadly used in ophthalmic diagnostics. The current generation of OCT systems enables reliable acquisition of volumetric scans containing information about the thicknesses of the various retinal layers. Thus, monitoring layer thickness changes is the main quantitative analysis performed by...
Article
We demonstrate Adaptive optics - Optical Coherence Tomography (OCT) with modal sensorless Adaptive Optics correction with the use of novel Adaptive Lens (AL) applied for in-vivo imaging of mouse retinas. The AL can generate low order aberrations: defocus, astigmatism, coma and spherical aberration that were used in an adaptive search algorithm. Acc...
Article
Full-text available
Animal models of human diseases play an important role in studying and advancing our understanding of these conditions, allowing molecular level studies of pathogenesis as well as testing of new therapies. Recently several non-invasive imaging modalities including Fundus Camera, Scanning Laser Ophthalmoscopy (SLO) and Optical Coherence Tomography (...