I remember when the first discussion of intrinsically photosensitive retinal ganglion cells (ipRGCs) started coming out. My thinking at the time was: “Wow, cool concept… but how in the world could you stack enough opsins in two membranes to make for any psychophysical perception?” In short, despite some years of predicting their presence, I did not buy it until the number of papers coming out made it impossible to refute. Now we have different classes of ipRGCs with multiple targets and the whole prospect is really interesting.
A couple of months ago, King Wai Yau gave a talk here at the University of Utah where he talked about some of his work and the number of ideas that came out of that talk were amazing. The idea that there are parallel pathways to conscious vision have been around for some time (blindsight etc…), but new work suggests possible image forming roles.
We’ve had a chapter in Webvision on melanopsin ganglion cells by Dustin Graham for some time, but this review by Gary Pickard and Particia Sollars also does a pretty nice job of summarizing ipRGCs, the discovery of melanopsin, its comparison of invertebrate and vertebrate photoreceptors, the mechanism of drive and some description of subtypes as well as current progress. Continue reading “Interesting Review: Intrinsically Photosensitive Retinal Ganglion Cells”
The desire to restore vision, once lost is as old as man itself.
This article by Noah Shachtman in Wired’s Danger Room documents the discovery of a 250 year old code complete with secret society. Its interesting reading from a variety of perspectives and has some wonderful photographs of the text and “blindfold goggles”, but what piqued my scientific interest was the ritual involving the restoration of sight and the potential evolution of the study of vision.
Sight and the mysteries of how we see is an equally compelling story that has inspired many throughout history to form in groups to discuss and study vision. The Greek Empedocles in the fifth century BC had his “Emission theory” of vision which evolved through the Aristotle and Galen. Plato also maintained that the eye possessed an “inner fire”. But it was not until Alhazen and Leonardo DaVinci that experiments were carried out and documented that we started to establish our understanding of sight. The Oculists mentioned in this article were thought to be early gatekeepers of the study of ophthalmology who would keep “charlatans” at bay that might cause people to lose their sight. These Oculists came after William Briggs Theory of Vision and organized themselves into one of the many secret societies that exploded throughout the world in the 18th century, some of which served as safe houses for the discussion of science and religion which did not necessarily fit within popular belief or practice. Of course modern understanding of vision was due largely to Hermann von Helmoltz in the 19th century which gave us early color theory and perception experiments, but it would be interesting work to follow the study of ophthalmology from the Oculists in the 18th century through Helmhotz work in the 19th century as it appears to be a partially secret history documenting the early study and restoration of vision loss.
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.
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”
Phototransduction is the process by which photon capture by opsins in photoreceptors is transduced into a neural signal. However, there are limits on visual sensitivity that are imposed by thermal means as opposed to the photochemical mechanisms resulting in activation of the phototransduction cascade.
The mechanism of this limit has long been a matter of debate, however this paper by Samer Gozem, Igor Schapiro, Nicolas Ferré and Massimo Olivucci demonstrates a mechanism. Mechanistically, the authors examined the maximum absorption wavelength (λmax) and the thermal activation kinetic constant (k) of different visual pigments which indicates that the thermal and photochemical activations are related. The authors found that rod opsin or rhodopsin possesses a transition state for thermal activation that has the same electronic structure as it does for photo-excitation. This results in spontaneous and random signals being generated in the rod photoreceptors that impose limits on visual sensitivity. Continue reading “Notable Paper: The Molecular Mechanism of Thermal Noise in Rod Photoreceptors”
A friend of mine (and amazing landscape/nature photographer) Jim Goldstein sent me a Tweet and pointed out simmering new conjecture in the art community that Vincent Van Gogh might have been color blind, specifically a protanope. I seem to remember some discussion of this years ago, particularly given that one can rather nicely simulate both protanopia and deuteranopia in Adobe Photoshop with built in filters (View>Proof Setup>Protanopia/Deuteranopia). However, the current speculation comes about from Kazunori Asada who wrote up a Tumbler blog entry here describing how he came about his idea and a subsequent app he wrote to simulate color vision and color blindness. The image above shows Kazunori Asada’s approximation of Van Gogh’s Starry Night and Flowering Garden with Path with the original on the left and the Asada transform approximation on the right.
Continue reading “Was Van Gogh Colorblind?”
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.
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”
This study by Mark E. Pennesi, Keith V. Michaels, Sienna S. Magee, Anastasiya Maricle, Sean P. Davin, Anupam K. Garg, Michael J. Gale, Daniel C. Tu, Yuquan Wen, Laura R. Erker, and Peter J. Francis documents the use of SD-OCT as a robust, non-invasive method for monitoring retinal changes in vivo in rodent models of retinal degeneration. The approach is so good that it can discriminate retinal detachment differences in different models of retinal degeneration (rd1 and rd10) that share defects on the same gene.
While histology is still the gold standard, this paper documents the further push of new technologies into in vivo approaches of monitoring. Perhaps we’ll get another boost with 2-photon/OCT approaches coming onto the scene…
Michalis Agathocleous, Nicola K. Love, Owen Randlett, Julia J. Harris, Jinyue Liu, Andrew J. Murray and William A. Harris have published a very interesting story on proliferating cells of the Xenopus laevis retina that documents aerobic glycolysis rather than oxidative phosphorylation. Historically, this shift in metabolism was termed the Warburg effect where it was originally described in tumorigenesis. Could it be that this shift in metabolism is more widely used than previously anticipated? Certainly in the proliferating developing Xenopus laevis retina, it appears so, even in the presence of oxygen. The only other instance of aerobic glycolosis I am aware of is in T-cells, but that too is associated with oncogenicity.
This really opens up possibilities for metabolic control of a variety of processes in not only development, but also pathology with respect to alternative methods for defining metabolic states and deriving energy.
1. Stare at the gray dot on the woman’s nose for 30 seconds (click on image for larger size).
2. Look quickly at the gray box below (or look at a plain surface like a ceiling or blank wall).
3. Blink repeatedly and quickly. Continue reading “Your Brain Develops The Negative”