Portrait Of Vision Scientist: Stuart Mangel, Ph.D.

Stuart-Mangel

This image of Stuart Mangel was made in Berlin, Germany at the 2012 ISER meeting.  Stuart is Professor in the Department of Neuroscience at Ohio State University.  Stuart came out of John Dowling’s lab at Harvard and has contributed mightily to our understanding of synaptic plasticity, circadian rhythms and retinal circuitry/information processing in the retina.

Its amazing how few people in the CNS community make the link between brain and retina, but Stuart has been one of the strongest proponents of understanding CNS in the context of retinal study.  This is important not just from the perspective of the CNS, but also so that we have a fundamental understanding of how the retina works in health and disease.  Finally, Stuart’s lab is one of those few labs that also understands the importance behind an understanding of retinal circuitry, but also how that circuitry results in information processing.  His work in how directional selectivity functions will be critical in elucidating how neural systems handle data streams encoded through the visual system.

 

 

 

Image Credit: Bryan William Jones, Ph.D.

The Cilium

Cilium_600

With the exception of a few types of cells, (acinar cells, T lymphocytes and hepatocytes), every cell in your body has a cilia.  In the vision community, we are used to seeing these structures in the distal portion of the photoreceptors.  The reality is that every cell in the retina has a cilium and some cells use the cilia as a means to expand a very specialized function like the photoreceptor outer segment or the hair cell or the respiratory epithelium of the lung.  This particular cilia was found in an amacrine cell in a rat retina.

Cilia were thought for a long time to be vestigal organelles that are formed in development, then left over after the developmental process ended.  Prachee Avasthi Crofts in the Wallace Marshall laboratory notes that “cilia are signaling centers capable of sensing a variety of extracellular stimuli: fluid flow in the kidney, odorants in olfactory neurons, and hormones in the satiety center of the brain.  Motile cilia in the trachea and brain ventricles can also generate flow of mucus and cerebrospinal fluid respectively.  Dysfunction in conserved ciliary structure and function therefore results in a variety of disorders (termed ciliopathies) which include polycystic kidney disease, anosmia, obesity, bronchiectasis and hydrocephalus, to name a few.

In the retina, the outer segments of photoreceptors that sense light are in fact modified sensory cilia with conserved mechanisms of formation and maintenance. Thorough characterization of phototransduction proteins that reside in the outer segment as well as rapid turnover of outer segments to recycle spent membrane and protein make this system an excellent model to study cargo transport within cilia. Furthermore, a hallmark of many pleiotropic ciliopathies is retinal degeneration that results from abnormal photoreceptor cilia function. Investigation of photoreceptor cilia dysfunction can yield much insight into generalized mechanisms of cilia-related pathogenesis and potential avenues for therapeutic intervention”.

In the retina, the applications being explored by a number of labs including Jun Yang’s laboratory here at the Moran Eye Center and by a recent student who’s work on Senior-Loken Syndrome in Wolfgang Baehr’s laboratory.  This is in addition to a number of labs throughout the world including Joe Besharse at the University of Wisconsin Madison, and Uwe Wolfrum at the University of MainzDavid S. Williams, University of California Los AngelesMarius Ueffing, University of TübingenEric A. Pierce, Harvard Medical School, Gregory J. Pazour, University of Massachusetts Medical School, Nicholas Katsanis, Duke University, USA,  Tiansen Li, NEI and many others.

 

New Webvision Chapter: Evolution of Phototransduction, Vertebrate Photoreceptors and Retina

Branchiostoma_lanceolatum

After much work by a number of our contributors, not the least of whom is the author of this particular effort, we have a spectacular new addition to Webvision:  A section on the Evolution of Phototransduction, Vertebrate Photoreceptors and Retina by Trevor D. Lamb.  Be sure to check it out and let us know what you think in the comments.

Continue reading “New Webvision Chapter: Evolution of Phototransduction, Vertebrate Photoreceptors and Retina”

Constructive Retinal Plasticity After Selective Ablation of the Photoreceptors

Photocoagulation_

This abstract was presented today at the Association for Research in Vision and Opthalmology (ARVO) meetings in Seattle, Washington by Corinne N. Beier, Bryan W. Jones, Philip Huie, Yannis M. Paulus, Daniel Lavinsky, Loh-Shan B. Leung, Hiroyuki Nomoto,  Robert E. MarcDaniel V. Palanker, and Alexander Sher. Continue reading “Constructive Retinal Plasticity After Selective Ablation of the Photoreceptors”

Building Retinal Connectomes

Connectomics image

There has been quite a bit of discussion of connectomes in the last while with President Obama’s new BRAIN initiative.  It is important to consider some of the requirements of obtaining a true synapse level wiring map in the brain as many are articulating from this initiative.  While there are new technologies that will be required to undertake this initiative for mapping the entire brain, the NIH NEI has been funding an ongoing project to study retinal circuitry which guides the community in how to approach a true synapse level map of the nervous system.

An example of this work  in Current Opinion in Neurobiology titled Building Retinal Connectomes is a review that illustrates the importance of having a complete network graph of connectivities in the retina and by extension other neural systems.  Complete network graphs are what will be required to understand how retinal systems (and any neural system) is constructed.  Even though the retinal community understands how retinas are wired in broad strokes, the precise, fine details are critical and elucidating them requires a new level of complete annotation derived from advances in light and ultrastructural imaging, data management, navigation and validation.

Authors are Robert E. Marc, Bryan W. Jones, J. Scott Lauritzen, Carl B. Watt and James R. Anderson.

 

Notable Paper: Paired-Pulse Plasticity In The Strength and Latency of Light-Evoked Lateral Inhibition to Retinal Bipolar Cell Terminals

Paired Pulse plasticity

I’ve been doing some reading in plasticity recently and found this paper in the Journal of Neuroscience by Evan Vickers, Mean-Hwan Kim, Jozsef Vigh, and Henrique von Gersdorff published last summer that looks at short term plasticity in the Inner Plexiform Layer mediating light adaptation.  Working in goldfish (Carassius auratus auratus) retina (an amazing retina), Vickers et. al. used patch clamp recordings on Mb bipolar cell terminals with paired-pulse light stimulation.  The idea was to examine and quantify plasticity in GABAergic lateral IPSCs with findings that show variation in the synaptic strength and latencies which correspond to adaptation and sensitization to surround temporal contrast.  The authors found that there are separate retinal circuitry pathways, each with differing mechanisms of plasticity that help to tune temporal response curves with glutamate release from ON bipolar cell terminals.  They conclude that “Short-term plasticity of L-IPSCs may thus influence the strength, timing, and spatial extent of amacrine and ganglion cell inhibitory surrounds”.

 

Interesting: The Spatial Organization Of Cholinergic Mosaics In The Adult Mouse Retina

Cholinergic Strettoi

This Short Communication published in the European Journal of Neuroscience back in 2000 by Lucia Galli-Resta, Elena Novelli, Maila Volpini and Enrica Strettoi was a paper I did not know existed.  That said, I ran into it the other day looking for some reference material and found it to be quite useful.  This communication represents an analysis of the cholinergic amacrine cell mosaics in the C57Bl6/J murine retina.  It served as a useful baseline for cell positioning, and cell mosaicing in both cholinergic arrays of the retina and is a nice analysis that should serve as a reference point for future genetic analysis studies in normal and pathological retinal tissues.  Enrica Strettoi’s laboratory has been carefully exploring the functional organization of the retina for some time now in the normal and pathological states and its always a joy to discover her work in the literature, even if it is 13 years old.

 

Interesting Paper: Gene Expression Changes Within Müller Glial Cells in Retinitis Pigmentosa

Retinal degenerations are accompanied by retinal remodeling events.  These events alter the structure and function of the retina and involve to a large extent, Müller cells which seem to serve as pathways for neuronal migration.  This paper by Karin Roesch, Michael B. Stadler and Constance L. Cepko looks at gene expression changes in the Müller cells, one of the glial cells of the retina as the rd1 mouse retina degenerates.

While the paper is not terribly conclusive in its definition of genes or pathways involved, (partially I suspect because of the limited time points examined and the late point in the examinations), this paper does however point in a direction that is useful to the retinal degeneration community.  Specifically, Müller cells are fundamentally involved in the remodeling process.  Intervening there is an opportunity to arrest or slow down the retinal remodeling process to allow for interventions and understanding which genes are involved is a good first step.

Interesting Paper: Creatine Transporter Immunolocalization In Aged Human And Detached Retinas

This manuscript by Clairton F de Souza, Michael Kalloniatis, David L Christie, Philip J Polkinghorne, Charles N J McGhee and Monica L Acosta examines the distribution of creatine transporter in the aging human retina, particularly after retinal detachment.  The questions behind this paper have ultimately to do with examining markers of energy metabolism in the retina and any impact on pathology in the retina (and be extension into the brain).  Creatine and phosphocreatine are intimately involved with maintenance of ATP levels and are therefore found in high concentrations in tissues that maintain high metabolic loads, like the retina.  Creatine is obtained from the diet and maintained in cells with an uptake pump, plasma membrane creatine transporter (CRT) that transports creatine from the blood/serum into the cell.  The maintenance of creatine is of fundamental importance in a variety of pathological conditions and as such is an area of hot interest in neuroprotection and supplementation. Continue reading “Interesting Paper: Creatine Transporter Immunolocalization In Aged Human And Detached Retinas”

The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells

This is an important issue for anyone involved in using murine models of retinal degeneration.  It turns out that contamination of Rd8 mutation in the B6 mice is more wide spread than the C57BL/6N mice.  Labs worldwide are going to have to reassess their data due to this mutation and all reviewers will ask about this in the immediate future.  The genotyping analysis of a variety of vendor lines is described in this paper by Mary J. Mattapallil, Eric F. Wawrousek, Chi-Chao Chan, Hui Zhao, Jayeeta Roychoudhury, Thomas A. Ferguson, and Rachel R. Caspi.  The take home message is that the rd8 mutation is in the C57BL/6N strain which is used worldwide to produce transgenic and knockout models.  The implications for non-vision labs are not as clear, but for vision labs, substantial disease can be present unrelated to another specific disease gene and will need to be accounted for.

Undersized Dendritic Arborizations in Retinal Ganglion Cells of the rd1 Mutant Mouse: A Paradigm of Early Onset Photoreceptor Degeneration

This paper by Devid Damiani, Elena Novelli, Francesca Mazzoni and Enrica Strettoi documents continued negative plasticity in retina by examining ganglion cells in the rd1 mouse.  The rd1 mouse is one of many models of retinal degenerative disease, in this case as an autosomal recessive retinal degenerative disease.  This work gets at the remodeling issue in retinal degenerative diseaseby examining the last cells in the chain of retinal cells that process information before sending it out to the brain and other CNS centers for further processing.   Continue reading “Undersized Dendritic Arborizations in Retinal Ganglion Cells of the rd1 Mutant Mouse: A Paradigm of Early Onset Photoreceptor Degeneration”

Astrocytes and Vasculature

This laser confocal image shows a GFP transgenic mouse retina under the control of the GFAP promoter stained with anti-Collagen IV (blue), anti-GFAP (red) and anti-GFP (green).  These labels not only show the spatial relationship of individual astrocytes to one another, but also the vasculature.   Image provided by Gabriel Luna out of the Steve Fisher and Geoff Lewis’s retinal cell biology group at UC Santa Barbara Neuroscience Research Institute.