In Webvision news, we have gone through some changes here, mostly under the hood, though some will have changed the appearance of Webvision subtly.
Webvision has now migrated to a new server. Most of the lifetime of Webvision has been running on Macintosh OSs of various flavors. But with the deprecation of Apache in the latest OS X Server, the writing was on the wall and I moved Webvision to a new server, running Linux. My thanks to the Moran Eye Center for helping with the costs of securing a new server.
Additionally, with consulting help from Anesti Creative, we have optimized Webvision, creating a responsive website for more platforms and increased the security, which these days unfortunately is necessary given the increased number of attacks literally every minute of the day from around the world.
We have endeavored to make this as easy as possible for end users, and hopefully these changes will result in an easier to use website, particularly from mobile devices and tablets.
Zhuo-Hua Pan, Edward T. and Ellen K. Dryer Endowed Professor; Professor of Dept. of Ophth., Vis. Anatomical Sciences; Scientific Director, Ligon Research Center of Vision, Kresge Eye Institute; Wayne State University School of Medicine; Wayne State University School of Medicine will be delivering a seminar on “Optogenetic Approaches for Vision Restoration” on Wednesday October 10th at 12:00pm in the Moran Eye Center auditorium. He will also deliver a Grand Rounds Presentation at 8:00am, also in the the Moran Eye Center auditorium.
Abstract: Severe loss of photoreceptor cells in inherited or acquired retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, can result in partial or complete blindness. My laboratory has been exploring and developing optogenetic approaches to treating blindness by expressing genetically encoded light sensors, such as channelrhodopsin- 2 (ChR2), in surviving inner retinal neurons to impart light sensitivity to retinas that lack photoreceptor cells. Proof-of-concept studies have demonstrated the feasibility of restoring retinal light responses and visually guided behaviors in animal models. Optogenetic therapy using ChR2 for vision restoration is currently in clinical trial. Our ongoing efforts focus on the development of better ChR variants and effective treatment strategies. In particular, we recently employed a transgenic blind mouse model combining with animal behavioral assays, which enables us to quantitatively assess the efficacy of different optogenetic tools and retinal targeting strategies, as well as to investigate the impact of retinal remodeling on optogenetic vision restoration.
Question: How small can the blood vessels in our retinas get?
Answer: Smaller than the diameter of a red blood cell (~6-8µm wide).
The red blood cells have to fold themselves to get through the tightest of spaces and line up, single file to get through the smallest retinal capillaries.
Image originally posted here.
Ocularists are specialists that mix art and science to create artificial eyes. The profession has existed since the 5th century and is one we don’t often hear about, yet it is a service for people to create a cosmetic artificial replacement eye that is tremendously important. We’ve featured the work of David Carpenter before here on Webvision, and now there is a wonderful post over on Spitalfields Life about David Carpenter, the Chief Ocularist at the Moorfields Eye Hospital with wonderful photography by Patricia Niven (@PatriciaNiven).
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.