Of course we know now that there are multiple visual pathways and each one of these visual pathways mediates a different aspect or derivative of a component of vision. It turns out that vision is complex, more complex than simply carrying “visual pixels” to the brain to be mapped out topologically. After photon capture by the photoreceptors of the eye and pre-processing operations in the circuitry of the retina, information is passed to the retinal ganglion cells or the output cells of the retina. Each one of the 18-20 types of ganglion cells that project out of the retina through the optic nerve mediates different kinds of information. Aside from projections to the primary visual cortex, some ganglion cells project to the lateral geniculate nucleus, others to the superior colliculus, the pretectum, the suprachiasmatic nucleus and the hypothalamus. Each one of these projections out of the retina carries information relevant to a different feature of vision. Some of these functions help control the size of your pupil limiting the amount of light that comes into the eye. Other projections help you orient your head and eyes to the world around you while other projections still help you figure out what time of day and season it is. Most of these meta-visual functions are not conscious, but play crucial roles in how we live our everyday lives and are only revealed when things in the visual system go awry like the man Oliver Sacks described who could catch a ball despite being completely and functionally blind. Milena Channing’s experience with a stroke in her visual cortex reveals some of this unconscious aspect of seeing, ironically by causing blindness while preserving portions of the brain involved in motion detection.
I had the honor and privilege of attending a Lasker/IRRF Initiative’s plenary session on Restoring Vision to the Blind at Janelia Farm last month where Mr. Sanford D. Greenberg delivered an emotional and inspiring story of a time in his life where he lost his vision during his junior year at Columbia University. The prospect of losing vision is absolutely and completely life altering for those affected as well as for those around the individual who has lost partial or complete sight. Mr. Greenberg’s story in his words, reveals the raw emotion of blindness, the fear and angst as well as the compassion and love of those who travel through life alongside us. At the end, there is also a surprise that will speak to aficionados of music and give some deeper insight into someone who has touched untold millions around the globe through their work and music.
This video is documentation of that event sent along for Webvision to share with you and the wider community by John Dowling the Chair of the Lasker/IRRF Initiative, and Janelia Farm who captured the video, the Lasker Foundation, the International Retinal Research Foundation and End Blindness by 2020. We are grateful to Mr. Greenberg for sharing his story and allowing us to help spread his story and mission of ending blindness here on Webvision.
On a personal note: While I have friends who are blind or are going blind, Mr. Greenberg’s talk haunted me the night after I saw it, particularly because of the field of science I am engaged in. Every scientist studying vision and diseases affecting vision should have the opportunity to spend time with those who have lost sight. It is important for people in the sciences to sit down and talk with those affected by the disease they study. I found this out this week after a meeting with a colleague who agreed to speak with a mutual friend who has Usher’s Syndrome. When my colleague stated after the meeting that they had never actually sat down to talk with someone who has the disease that they study, I was initially surprised. This is not uncommon though. As scientists, not just in the vision sciences mind you, we obsess about the details of what we study and are absolutely driven by the work, but do not always look around and talk with people who’s diseases are the subjects of our studies. This is fundamental to the process as it drives home the motivation for the long hours, late nights and frustrations with grant funding. It forces an introspection and helps us to better communicate our work to a wider audience which is critical to science progress and funding.
Andrew Bastawrous shares with TED a wonderful example of using smartphone technology to screen vision in remote parts of the world, bringing eye care to some of the 39 million people in the world who are blind.
I ran across an interesting paper in PLOS One published back in March of 2012 by Parameswaran G. Sreekumar, Christine Spee, Stephen J. Ryan, Susan P. C. Cole, Ram Kannan and David R. Hinton. This manuscript looks at a mechanism of retinal pigment epithelium (RPE) cell death with notable findings identifying therapeutic targets for disorders that involve the RPE cells.
The authors tested whether α-crystallin has a protective effect that is influenced by changes in glutathione (GSH) content while exploring the mechanism of glutathione efflux from the cells. Interestingly, they found that the multiple multidrug resistance proteins (MRP) were expressed in RPE, particularly MRP1 and that it is MRP1 that mediates GSH (reduced form) and GSSG (oxidized form) efflux from the RPE cells. In addition, they noted that inhibition of MRP1 makes RPE cells resistant to oxidative stress induced cell death pathways and conversely, over expression of MRP1 renders them more susceptible to oxidatively induced cell death pathways. Finally the authors note that α-crystallin’s antiapoptotic function is mediated by both GSH and MRP1.
An interesting report in the New England Journal of Medicine describes electrical burns to the eyes of a 42-year old electrician which caused star-shaped cataracts to form in the lenses. The electrical burn resulted from the gentleman’s shoulder coming into contact with 14,000 volts. Lens replacement helped mediate some of the vision deficit, but there was also retinal and optic nerve atrophy and damage.
A new manuscript in the Journal of Clinical Investigation (on the cover) by Peter D. Westenskow, Toshihide Kurihara, Edith Aguilar, Elizabeth L. Scheppke, Stacey K. Moreno, Carli Wittgrove, Valentina Marchetti, Iacovos P. Michael, Sudarshan Anand, Andras Nagy, David Cheresh and Martin Friedlander at The Scripps Research Institute describes a new technique for treating aberrant growth of blood vessels in the retina from disease processes like “wet” macular degeneration and diabetic retinopathy, two leading causes of blindness. The approach involves manipulating disease processes with short RNA strands that precisely target microRNAs (anti-microRNAs if you will) to stop the aberrant blood vessel grown without harming the existing retinal vasculature. The results of this study showed that treatment with microRNAs “blocked aberrant vessel growth without damaging existing vasculature or neurons in three separate models of neovascular eye disease—a proof-of-principle that suggests future treatment based on the same approach may be effective in humans.”
Essentially, Onecut1 is critical for the formation of horizontal cells, but of fundamental importance to retinal degenerative research, this work implies that horizontal cells might be necessary for the survival of photoreceptor cells. Of course we have known for some years that horizontal cells are some of the very first cells to respond to retinal degeneration by extensively remodeling, but this is an interesting result that suggests a direct dependence of photoreceptors on the horizontal cells themselves for survival.
The Levine lab here at the Moran Eye Center has a new publication out in the Journal of Neuroscience and even scored the cover. Specifically, the manuscript was authored by Patrick J. Gordon, Sanghee Yun, Anna M. Clark, Edwin S. Monuki, L. Charles Murtaugh, and Edward M. Levine. The Levine team explored how multipotent retinal progenitor cells (RPCs) control the ordered production of the major cell types in the mouse retina. The key finding in this manuscript is that the Lim/Homeodomain protein, Lhx2, is a progenitor-intrinsic regulator of maintenance/self-renewal, precursor production, and competence progression. They arrived at this conclusion by generating Lhx2 conditional knockout mice at multiple stages of development using an inducible Cre-driver (Hes1CreERT2) that specifically targets progenitor cells. This approach allowed them to perform day-by-day inactivations, achieving a temporal scale of gene expression control not previously reported in the retina. This is an important advance because the properties of RPCs are constantly changing, and we are now able to directly test the regulation of these properties in an appropriate temporal manner. As such, The Levine team has identified Lhx2 as an RPC-intrinsic factor that regulates maintenance, precursor fate, and competence simultaneously.
The animated image above is a sequence of abstracted neuronal images from brain visual cortex that I originally posted here. The images are from neurons labeled with different probes, though that is not important for the discussion here. What is relevant is that I’ve been wondering why science does not more widely implement animated GIFS to explain and represent scientific image data for ease of communication. The .gif format is one of the oldest standards on the Internet for display of raster graphics, introduced by Compuserve back in 1987. In addition to their long history on the Internet, .gif files have wide support and are incredibly portable. (The history of the gif is summarized nicely here on a PBS Off Book video on Youtube). Animated gifs have made a resurgence of sorts on the Internet as a means to communicate or show motion in ways that were not originally intended, but nevertheless are innovative and useful. It would seem that for scientists and those interested in communication of scientific ideas, supplemental data are an ideal way to show animation or motion or any number of approaches useful to scientific communication. Granted, one can do all sorts of animations with video formats like MPEG or Flash (not very convenient for portable uses like phones or tablets) and new HTML5 and emerging HTML standards, but the gif is a robust standard that has been around for many years and can be utilized by those in parts of the world where bandwidth and some of the latest tools are not as available as they are in 1st world countries.
As science and science education becomes more available via open access to wider audiences around the globe, we should strive to adopt open standards with low to reasonable standards for accessibility and gifs fit nicely within those requirements.
I ran across this interesting vignette from Astronaut Cmdr. Hadfield (his Twitter account here) on how sight changes in space including the flattening of eyeballs, swelling around the optic nerve and the random flashes of light seen by astronauts.
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”.