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Seminar: Human CFH Risk Variant Induces AMD Pathology In Mice

Catherine Bowes Rickman, Professor of Ophthalmology and of Cell Biology at Duke Eye Center, Duke University School of Medicine will be delivering a seminar on “Human CFH Risk Variant Induces AMD Pathology In Mice” on Wednesday, May 23rd at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: Age-related macular degeneration (AMD) is the most common cause of blindness among elderly people in the developed world. There is a growing body of evidence based on biochemical, genetic and cell biology that implicates the alternative pathway of complement in the development of AMD. In particular, the complement factor H (CFH) gene, where a nucleotide change results in a tyrosine (Y) to histidine (H) exchange in short consensus repeat 7 (amino acid 402), increases the AMD risk dramatically. CFH is the soluble regulator of the alternative pathway of complement, and is essential in slowing the spontaneous proteolysis or “tickover” of C3→C3b in the plasma. Although it is now apparent that dysregulation of the complement cascade, and of the alternative pathway in particular, is an important predisposing step in AMD development – how to best target complement dysregulation pharmacologically remains undefined. A critical unmet need is to provide evidence supporting the use of therapies targeting complement inhibition for dry AMD in relevant AMD models. We have developed AMD mouse models that faithfully recapitulate many aspects of AMD that – like AMD – are based on multiple risk factors including advanced age, immune system dysregulation and consumption of a high-fat, cholesterol-enriched Western- style diet. These chronic early/intermediate AMD models provide the first opportunity to test the efficacy of targeted immune-based therapies. These models will also likely help to unravel why therapies targeting complement proteins have had limited success in treating humans with AMD to date. I will be describing these models and the outcomes of preclinical testing of therapies targeting the complement system.

Categories: Seminar.

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Seminar: Retinal Pigment Epithelial Cell Bystander Effects Contribute to AMD Pathology

Barbel Rohrer, the SmartState Endowed Chair in Gene and Pharmacological Treatment Of Retinal Degenerative Diseases at Medical University South Carolina will be delivering a seminar on “Retinal Pigment Epithelial Cell Bystander Effects Contribute to AMD pathology” on Wednesday, April 18th at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: Retinal pigment epithelium damage in age-related macular degeneration is triggered in many different locations, suggesting that damage occurs in susceptible areas, while delaying damage in more resilient areas. I will be describing experiments to distinguish two different mechanisms that would mediate the bystander effect: transfer of a signal to the recipient cells by exosomes; or the spread of information by means of communication via gap junctions.

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Seminar: Diverse Glycinergic Receptor Subunits & Retinal Ganglion Cell Visual Function

Maureen A. McCall, Professor and Kentucky Lions Eye Research Endowed Chair, at University of Louisville will be delivering a seminar on “Diverse Glycinergic Receptor Subunits & Retinal Ganglion Cell Visual Function” on Wednesday, March 21st at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: In the retina excitatory signaling lays down the basic foundation of visual processing and inhibition shapes excitation to produce the diverse visual responses of its almost 40 different ganglion cell types. Much of inhibition occurs from the inputs of the ~50 amacrine cells (ACs). Approximately half of these amacrine cells are GABAergic and the others are glycinergic. This is unlike the rest of the CNS, where either GABA or glycine is the primary inhibitory neurotransmitter and there are fewer interneurons. AC inputs mediate feedforward, feedback, crossover and serial inhibition that ultimately shape the excitatory output of bipolar cells (BCs), as well as the responses of GCs. In general, GABA inhibition refines spatial responses (object size, shape and location in space and direction of object motion and glycine inhibition shapes temporal responses (object motion and velocity, and the timing of responses to standing contrast. This is a simplistic view, belied by recent studies suggesting that each AC type may uniquely shape visual function and by extension must be crucial to mechanisms that control the diversity of visual responses of the ~40 GC types that form parallel processing channels and establish the framework for all subsequent vision. We know from BCs that inhibitory diversity is enhanced by expression of different inhibitory subunits with different deactivation kinetics, e.g., GABAA, GABAC and. A role for GlyRα subunit diversity is clear in both spinal cord and brainstem, where individual.

GlyRαs create a variety of synaptic interactions to tune the postsynaptic response and modulate different functions15-17. Because the retina has a wider diversity of interneurons (ACs), and it is the only structure that expresses all 4 GlyRα subunits, in addition to GABARs, we hypothesize that this variety contributes substantially to GC visual function. I will discuss the distribution and function of glycinergic receptor isoforms across the retina and retinal ganglion cells. I will describe what we have found about the roles of glycine subunit specific inhibition in shaping the visual responses of retinal ganglion cells.

Categories: Seminar.

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Seminar: A Form of Control: TRPV4 Channels in the Eye

Nicholas A. Delamere, Professor and Head, Dept. of Physiology; Professor, Dept. of Ophthalmology & Vision Science, University of Arizona will be delivering a seminar on “A Form of Control: TRPV4 Channels in the Eye” on Wednesday, February 21st at 12:00 Noon in the  Moran Eye Center auditorium.


Abstract: Lens transparency requires precise maintenance of ion and water content (homeostasis), something that is difficult to achieve because of the unique properties of lens cells. The seminar will discuss how a particular type of ion channel, TRPV4, acts as a sensor in a remote control mechanism that makes homeostasis possible. The case will be made that lens TRPV4 is activated by mechanical forces. It will be argued that TRPV4 activation works like a switch that opens connexin hemichannels, causing the lens to release signaling molecules that adjust Na,K-ATPase activity in its epithelium monolayer. The significance to human well-being is that cataract is frequently associated with failed homeostasis. In a broader context, the seminar will review TRPV4 expression in other parts of the eye. The ciliary body also uses TRPV4 to sense and respond to mechanical stimuli, perhaps to adjust the driving force for aqueous humor secretion.

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Seminar: Photoreceptor Energy Metabolism Directs Neovascular Retinal Disease

Lois E. H. Smith, Professor of Ophthalmology at Harvard Medical School, Boston Children’s Hospital will be delivering a seminar on “Photoreceptor Energy Metabolism Directs Neovascular Retinal Disease” on Wednesday, March 14th at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: Neuronal energy demands are met by a tightly coupled and adaptive vascular network that supplies nutrients and oxygen. The retina is one of the highest energy-consuming organs, exceeding the metabolic rate of the brain; blood vessels grow and regress in reaction to changes in these high demands. Reduced nutrients and reduced oxygen availability instigate compensatory albeit misguided pathological neovascularization in proliferative retinopathies. Conversely, impaired retinal ganglion cell and photoreceptor survival are correlated with abrogated vascular development and as neurons degenerate, the retinal vasculature atrophies to match the reduced metabolic requirements. In mice, photoreceptor degeneration is associated with thinning of the choroid and inner retinal blood vessels. Conditions such as diabetic retinopathy, vaso-proliferative retinopathy of prematurity and neovascular age-related macular degeneration (AMD) have been characterized as diseases of the vasculature. However, it is becoming more evident that the metabolic needs of the neural retina profoundly influence blood vessel supply in development and in disease.

Retinal oxygen sources and the vaso-proliferative response to low oxygen levels have been well characterized. However, understanding the specific fuels used in the retina to generate ATP and supply building blocks for biosynthesis, as well as understanding the vaso-proliferative response to the lack of fuel are also key to neurovascular development. The metabolic and energy needs of the retina have been assumed to be met by glucose, as the retina is part of the CNS, and the brain relies almost exclusively on glucose. There are two primary pathways that cells can use to generate ATP from glucose, glycolysis and oxidative phosphorylation. However, Cohen and Noell concluded in 1960 that a substantial portion of the energy produced through oxidation by the retina (around 65%) was not derived from glucose. We recently showed that the retina (photoreceptors) can also oxidize lipid through fatty acid β-oxidation to produce ATP, accounting for the energy gap noted by Cohen. Both glucose and lipid metabolism are forces that shape the vascular supply of the eye in development and in vaso-proliferative eye diseases.

Categories: Seminar.

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Seminar: cGMP/PKG signaling regulation of endoplasmic reticulum homeostasis in CNG channel deficiency

Xi-Qin Deng, Associate Professor of Cell Biology, and the Joanne I Moore Professor of Pharmacology at University of Oklahoma Health Sciences Center will be delivering a seminar on “cGMP/PKG signaling regulation of endoplasmic reticulum homeostasis in CNG channel deficiency” on Wednesday, January 24th at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: Mutations in the CNGA3 and CNGB3 genes that encode the cone cyclic nucleotide-gated (CNG) channel subunits account for about 80% of all cases of achromatopsia and are associated with progressive cone dystrophies. Cone photoreceptors degenerate over time in patients and in mouse models of CNG channel deficiency. Over the last several years, my laboratory has been investigating the cellular mechanisms of cone degeneration using mouse models with CNG channel deficiency. Upon binding of cyclic guanosine monophosphate (cGMP) under dark conditions, CNG channels open and permit the influx of the calcium and sodium ions necessary to maintain the dark current and cellular calcium homeostasis. We have found CNG channel deficient-cones undergo endoplasmic reticulum (ER) stress-associated apoptosis. All three arms of ER stress are activated in CNG channel deficiency. We also showed elevated cGMP/ cGMP-dependent protein kinase (PKG) signaling in CNG channel deficiency and cone protection following cGMP depletion or PKG inhibition. Moreover, we obtained evidence connecting ER calcium channel dysregulation with ER stress and cone death. The current effort aims to determine the cGMP/PKG signaling regulation of ER homeostasis in CNG channel-deficient cones.

Categories: Seminar.

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Seminar: Living In The Cold – Hibernation And Retinal Neurobiology

Wei Li, Chief and Senior Investigator at the National Eye Institute/National Institutes of Health, Retinal Neurophysiology Section will be delivering a seminar on “Living In The Cold – Hibernation And Retinal Neurobiology” on Wednesday, December 18th at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: We are interested in understanding how the retina adapts to extreme metabolic conditions, such as those experienced by hibernating animals.  We believe that metabolism is one of the core issues pertaining to the health and pathological change in the retina.  By studying hibernating animals (the ground squirrel), we hope to identify strategies that can help the retina better cope with metabolic stresses that feature in retinal disease.  In this presentation, I will discuss several adaptive features of the ground squirrel retina during hibernation.

Categories: Seminar.

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Seminar: Retinal and Brain Circuits Underlying the Effects of Light on Behavior

Seminar Flyer-Hattar.ppt

Samer Hattar, Chief and Senior Investigator at the National Institutes of Mental Health/National Institutes of Health will be delivering a seminar on “Retinal and Brain Circuits Underlying the Effects of Light on Behavior” on Wednesday, September 6th at 12:00 Noon in the  Moran Eye Center auditorium.

Abstract: In this presentation, I will talk about how environmental light through photoreceptors in the retina reaches the brain to influence our internal ,timing, sleep, mood and learning. I will provide detailed retinal circuits, and new brain regions that are responsible for the effects of light on each aforementioned function. In the process, my presentation would be applicable to our modern lifestyle where we extended the day into the night by using artificial lighting and electronic devices that are delaying our sleep onset and leading to sleep disruption and debt. These changes could have major societal impacts that I am going to discuss.

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Paul Witkovsky, Vision Scientist, Artist

PaulWitkovsky painting

Many vision scientists seem to have a penchant for creating art, and Dr. Paul Witkovsky is no exception.  Paul is a famous vision scientist that spent most of his career at NYU New York City in the department of Ophthalmology. His research spanned the fields of retinal physiology, retinal ultrastructure and pharmacology.

His major contribution has been in trying to understand the role of dopamine in the retina and its role in light adaptation and cone vision.  This work he has passed on to his academic progeny including David Krizaj here at the Moran Eye Center, Bill Brunken at SUNY and Jozsef Vigh at Colorado State University.

Paul has always been a “renaissance man” interested in travel, languages, music and art as well as science.  Above, you can see one of his recent abstract paintings (acrylic).

Categories: Art of Vision.


Deep Learning Algorithm for Detection of Diabetic Retinopathy

Google image fundoscopy

A very cool paper was published in JAMA yesterday that is a result of Google Research asking if machine learning and computer vision could improve retinal fundoscopic examinations of patients with diabetic retinopathy.  The outcome of course is increased patient screening for physicians with limited resources.

Categories: Interesting.

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Nobel Prize Discoveries Pave Way for Curing Mind and Sight Diseases

Bright Focus AMD

The BrightFocus Foundation has a wonderful post out that describes Yoshinori Ohsumi’s Nobel Prize in Medicine awarded this year.  The post covers the work that led up to the Nobel as well as the applications of this work to diseases such as Alzheimer’s and Age Related Macular Degeneration (AMD) being explored by BrightFocus funded investigator, Debasish Sinha.

Categories: Interesting Links.

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Seminar: From Biomechanics to Proteomics – Toward the Mechanisms of Axonal Insult in Glaucoma


Seminar Flyer - Burgoyne

Claude Burgoyne, Van Buskirk Chair for Ophthalmic Research and Director of the Optic Nerve Head Research Laboratory at the Devers Eye Institute in Portland, Oregon will be delivering a seminar on “From Biomechanics to Proteomics – Toward the Mechanisms of Axonal Insult in Glaucoma” on Wednesday, November 16th at 12:00 Noon in the Moran Eye Center auditorium.

Dr. Burgoyne is a Glaucoma clinician scientist, Van Buskirk Chair for Ophthalmic Research and Director of the Optic Nerve Head Research Laboratory at the Devers Eye Institute in Portland, Oregon. After an undergraduate Bachelor of Arts degree in Architecture and Medical School at the University of Minnesota, he pursued Ophthalmology residency training at the University of Pittsburgh and Glaucoma Fellowship training at the Wilmer Eye Institute at the Johns Hopkins Hospitals in Baltimore, MD. For twelve years he was Director of Glaucoma Services at the LSU Eye Center in New Orleans before moving to Devers in 2005. For the past 19 years his laboratory has been NIH funded to study the effects of aging and experimental glaucoma on the neural and connective tissues of the monkey optic nerve head within 3D histomorphometric reconstructions. This work now extends to studying the cell biology of connective tissue remodeling and axonal insult early in the disease.
Building upon its 3D capabilities, his laboratory is also funded to use Optical Coherence Tomography (OCT) to visualize and quantify the deep tissues of the monkey and human optic nerve head and peripapillary sclera. The long-term goal of his work is to build a clinical science to predict how an individual optic nerve head will respond to a given level of intraocular pressure and the clinical tools to detect and treat that response.

Categories: Seminar.

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On The Way To RD 2016 and ISER 2016

Up In The Air To Japan

The Webvision crew is on our way to Japan for the RD 2016 and ISER 2016 meetings in Kyoto and Tokyo, Japan as we speak.  We are promoting the hashtags #RD2016 and #ISER2016 for the meetings.  If you want to meet to talk or arrange to have your work featured on Webvision, be sure to ping us at @webvision1 or @BWJones on Twitter before/during the meetings.




Categories: Events, Meetings.

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What It Looks Like To Be Colorblind, Part II


We’ve linked to posts before about what it looks like to people who are colorblind complete with animated gifs, but there is a new resource of gifs from the U.K.’s Clinic Compare that have a more film like quality and include a wider variety of color blindness forms.  We include a number of them below including green-blind/Deuteranopia, blue cone monochromacy, red-weak protanomaly, blue-blind/tritanomaly, green-weak deuteranomaly, monochromacy/acrhomatopsia, red-blind protanopia, and red-weak protanomaly.

gifs are rather large, so give them time to upload.

ht: @boingboing for the link.


Categories: Interesting.

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TRPV4 Regulates Calcium Homeostasis, Cytoskeletal Remodeling, Conventional Outflow and Intraocular Pressure

Krizaj glaucoma

Glaucoma is the main cause of irreversible blindness in the world. In most common types of the disease, the optic nerve is damaged by an increase in intraocular pressure (IOP) which blocks fluid drainage through canals in the eye. There is currently no cure, however, the disease can be treated by lowering IOP. Unfortunately, all IOP-lowering drugs that in the market today target the secondary drainage pathway which mediates only 5-15% of fluid outflow. Therefore, the main goal in glaucoma research has been to identify targets in the primary outflow pathway mediated through the trabecular meshwork tissue. David Krizaj’s group at the Moran Eye Institute (University of Utah School of Medicine) has done just that.

In a paper just published in Scientific Reports, they identify TRPV4, a mechanosensitive ion channel, as the main trabecular target of increased IOP. This highly collaborative project combined genetic, molecular, whole animal approaches with bioengineered nanoscaffold models of glaucoma and drug discovery to show that activation of the channel mimics the trabecular changes in glaucoma whereas elimination of the TRPV4 gene or systemic exposure to TRPV4 inhibitors protected mice from the disease. In collaboration with Glenn Prestwich’s group in Medicinal Chemistry at the University of Utah, the team synthesized new eye drops which lowered IOP to levels seen in control mice. By targeting the primary outflow pathway, this study promises to bring new, effective cures that complement current glaucoma treatment. The primary authors of the study are Dr. Dan Ryskamp, Amber Frye and Dr. Tam Phuong.

Categories: Moran Eye Center, Moran Eye Center Research, Notable papers, Retinal Disease.

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