Increase in Myopia Seen in U.K. in Prior Decades

Article: Rates of short-sightedness increasing in the UK
Source: University College London (U.K.)
Published: January 20, 2022
Article: We're Facing a Myopia 'Epidemic', Scientists Say. Here's Why
Source: ScienceAlert
Published: January 20, 2022
Article: UK rates of nearsightedness have increased significantly over time
Source: Medical XPress
Published: January 19, 2022

Termed the "myopia epidemic," countries around the world have noticed an increase in both the prevalence and severity of nearsightedness (shortsightedness) among their populations, especially among youth. Researchers in the U.K. looking at Biobank data of individuals born between 1939 and 1970 have also noted an increase in myopia in more recent decades, that is, a higher rate of myopia within their younger populations. In particular, the study analyzed data from 107,442 people and found that while 20% of people born between 1939 and 1944 were nearsighted, that rate increased to 29% among people born between 1965 and 1970. The researchers hypothesize an environmental factor to the rapid increase in the rate of myopia, or perhaps gene-environment interactions, since genes in themselves do not change that quickly. In studying the trend of myopia from the U.K. Biobank data, the investigators show that the increase in the prevalence of myopia is not limited to the past decade. The team also looked at demographic correlations and found a link between higher levels of educational attainment/intensity and nearsightedness, with the link becoming stronger over time. The investigators note that analyzing the difference between childhood-onset and adult-onset myopia would reveal more nuanced data, such as the effect of genes vs. environment; however, the findings did not point to a result consistent with that hypothesis, pointing instead to peak adult-onset myopia in a younger cohort. The authors stress the importance of awareness of myopia risk factors and preventative measures, especially as they correlate with educational intensity and could increase risk of ocular diseases (such as myopic degeneration and retinal detachment) if unchecked, and note that plateauing of myopia frequency points to the potential of effective intervention.

My rating of this study: ⭐⭐

Cumberland PM, Bountziouka V, Hammond CJ, et al. "Temporal trends in frequency, type and severity of myopia and associations with key environmental risk factors in the UK: Findings from the UK Biobank Study." PLOS ONE.  19 January 2022. https://doi.org/10.1371/journal.pone.0260993

"Retinal Age Gap" as Prediction of Aging and Mortality

Article: Your eyes hold the key to your true biological age
Source: CNN Health
Published: January 18, 2022
Article: Something in Your Eyes May Reveal if You're at Risk of Early Death
Source: ScienceAlert
Published: January 19, 2022
Article: Using AI to Assess Eye Scans, Scientists Find “Retinal Age Gap” Predicts Mortality Risk
Source: Genetic Engineering & Biotechnology News
Published: January 19, 2022

The eyes are not only the windows to the expression of one's inner thoughts, but also an early indicator of systemic health, from cardiovascular to neurological diseases. Recently, an international team of investigators applied computer deep learning to retinal imaging to analyze the difference between people's biological age of their retinas and their chronological age since birth. The study comprised of data from the U.K. Biobank of 80,169 fundus images taken from 46,969 adults between 40 and 69 years of age; data from 35,917 of the participants were assessed over a period of 11 years (while data from other participants were used to validate the accuracy of the deep learning model used). Termed the "retinal age gap," the difference could be used as a screening tool for overall health and risk of mortality, which is notable given that biological age varies from one person to another and could be a more accurate representation of health status than chronological age. In particular, within a 3.5-year overall accuracy, the study found that each 1 year increase in the retinal age gap was associated with a 2% increase in risk of all-cause mortality and a 3% increase in risk of cause-specific mortality attributable to diseases other than cardiovascular disease or cancer. Furthermore, a large retinal age gap of up to 10 years was associated with up to 67% higher risk of mortality. The two diseases for which the model did not find any significant association were cardiovascular disease and cancer, which the researchers think could be due to the small sample size of cases in the study population and to improvements in heart and cancer treatments. A clinical spokesperson of the American Academy of Ophthalmology comments, "The really unique aspect of this paper is using that difference in a patient's real age compared to the age the computer thought a patient was to determine mortality. This is not something that we thought was possible." The study highlights that the retina is also sensitive to the effects of aging throughout the body, and thus could be a potential biomarker of aging and mortality risk, but has the advantage of being accessible for monitoring of health easily and affordably through optical imaging and computer deep learning.

My rating of this study: ⭐⭐⭐

Zhu Z, Shi D, Guankai P, et al. "Retinal age gap as a predictive biomarker for mortality risk." British Journal of Ophthalmology.  18 January 2022. https://doi.org/10.1136/bjophthalmol-2021-319807

Apolipoprotein B100 as Protective Biomarker in AMD

Article: Study Finds Up to 30% of Patients with Wet Macular Degeneration Can Safely Stop Eye Injections
Source: Johns Hopkins Medicine
Published: January 18, 2022

Venn diagram of 172 key proteins in AMD

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals 50 years of age and older. "Wet" AMD, characterized by neovascularization and fluid leaking from blood vessels onto the retina, is the more severe form leading to most cases of vision loss. Current therapy consists of anti-vascular endothelial growth factor (anti-VEGF) injections monthly or every other month. Although effective at slowing progression and preventing vision loss, the method and frequency of therapy often present obstacles to patient adherence. Researchers sought to investigate the outcome of pausing anti-VEGF therapy, following 106 patients with wet AMD over a two-year study period; the patients themselves were treated by the research team from 2013 to 2020. Each patient underwent a customized anti-VEGF injection schedule, wherein the lead clinician determined whether the patients needed another injection at each visit or if they could enter a treatment pause. Eyes without treatment that showed no signs of fluid accumulation or advancing vision loss after at least 30 weeks of monitoring were considered safely weaned off anti-VEGF therapy. At the end of one year, 38 of 122 (31%) of treated eyes, or one-third of the patients, had stopped anti-VEGF therapy in at least one eye. Half of the patients, or 63 of 122 (52%) treated eyes, required injections only every 6–12 weeks, with a handful being weaned off of treatment at the end of year two. Patients who could pause therapy showed better outcomes. The lead clinician comments, "Across the board, the patients who could enter a treatment pause did the best even though they were receiving no anti-VEGF drugs. They had better visual acuity, better gain of vision and less fluid in their retina."

The investigators next looked at biomarkers that distinguished the patients who could be weaned off of treatment from those who required monthly injections to maintain their vision. Fluid samples from some of the patients, collected before the treatment plan and at subsequent visits, showed differences in the amounts of 172 proteins between the two groups. The researchers chose one protein, apolipoprotein B100, to study in further detail; apolipoprotein B100 had been demonstrated in other studies to be a part of drusen, deposits that accumulate under the retina and contribute to dry AMD. They found that apolipoprotein B100 was present in much higher levels in the eyes of patients who could be weaned off of anti-VEGF and also present in higher levels in patients who did not develop wet AMD compared to those that did, leading them to think that apolipoprotein B100 has a protective effect against wet AMD. This hypothesis was confirmed when mice genetically engineered to have higher levels of apolipoprotein B100 showed less abnormal blood vessel growth in the retina than mice with lower levels of the protein. Although apolipoprotein B100 was chosen as a proof-of-concept, the researchers add that other proteins could have similar protective effect and potential as therapeutic candidates. This being said, the lead clinician stresses that randomized clinical trials in a large group of patients with wet macular degeneration must happen before broader recommendations on pausing anti-VEGF therapies can be developed.

My rating of this study: ⭐⭐⭐

Cao X, Sanchez JC, Dinabandhu A, et al. "Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy." Journal of Clinical Investigation.  7 December 2022. https://doi.org/10.1172/JCI144469

Eye-Tracking Technology in Intensive Care Units

Article: Intensive care patients speak with their eyes
Source: Ruhr University Bochum (Germany)
Published: January 18, 2022

Communication by means of an eye-tracking system

Being voiceless can be a frustrating experience for patients in intensive care units, with hospital staff often needing to use alternative methods of nonverbal communication. However, eye-blinking, lip-reading, head nodding, or the use of pen and paper or alphabet boards are often insufficient. Inspired by the use of modern communication technologies for patients with advanced neuromuscular diseases, researchers in Germany are exploring eye-tracking systems to overcome similar communication barriers for critically ill intensive care patients, such as those who are ventilated or tetraplegic. The present study included 75 patients with an endotracheal tube or tracheostomy tube and a history of mechanical ventilation at a surgical intensive care unit, and employed a commercially available eye-tracking system and positioned in the patient’s line of sight. This mounted mobile system consists of near-infrared-emitting light sources that reflect off of the person's eyes and are captured by cameras, which is then relayed to image processing software that calculates the direction of the person's gaze. The system is individually calibrated to each user, and after a short training period, users can express some of their thoughts based on scales and scores shown on the monitor. Such technology revealed that the participants generally experienced poor quality of life, and poor state of health, though many considered themselves cognitively capable. The researchers emphasize that their technology can enable critically ill, non-verbal and movement-impaired people to communicate their self-assessment and feelings to others. Such technology can help to improve the interaction between patients and their hospital caregivers until they gain the ability to communicate independently.

My rating of this study: ⭐⭐🌸

Ull C, Hamsen U, Weckwerth C, et al. "The use of predefined scales and scores with eye-tracking devices for symptom identification in critically ill non-verbal patients." Journal of Trauma and Acute Care Surgery.  14 December 2021. https://doi.org/10.1097/TA.0000000000003494

Link_TSG6 for the Treatment of Dry Eye Disease

Article: Promising novel treatment for Dry Eye Disease revealed by new research
Source: University of Manchester (U.K.)
Published: January 13, 2022

Link_TSF6 compared with Restasis in an 
autoimmune (top) and environmental (bottom)
mouse model of dry eye disease

Characterized by the loss of homeostasis of the eye’s tear film and a vicious cycle of corneal epithelial damage and inflammation, dry eye disease (DED) is estimated to affect 350 million people worldwide. Symptoms include persistent eye irritation, blurred vision, and decreased quality of life. Researchers in the U.K. and South Korea are investigating a novel protein biological drug, Link_TSG6 (comprising the Link module of human TNF-stimulated gene/protein-6), in the treatment of DED. In a new study, they tested the drug on two mouse models of DED: an autoimmune model where mice spontaneously develop dry eye disease, and a desiccating stress model that mimics DED caused by environmental factors. They report, "Results from the study showed that topically administered Link_TSG6 (e.g., twice a day for 7 days) dose-dependently reduced corneal epithelial defects and suppressed inflammatory markers while increasing tear production and conjunctival goblet cell density. At the highest Link_TSG6 dose, no corneal lesions remained in approximately 50% of treated eyes. In addition, Link_TSG6 was significantly more effective than Restasis, the market leading treatment, at reducing corneal epithelial erosions and reducing inflammation." In particular, Link_TSG6 suppresses inflammatory cytokines on the ocular surface and inhibits the infiltration of Th1 and Th17 immune cells into the lacrimal glands and lymph nodes. The researchers are encouraged by the preclinical data and look to further the progress of their work in human clinical trials, stating, "The publishing of this research is a major accomplishment in our journey towards finding an effective treatment for Dry Eye Disease, which could improve the lives of millions around the world."

My rating of this study: ⭐⭐

Oh JY, Ryub JS, Kim HJ, et al. "The Link module of human TSG-6 (Link_TSG6) promotes wound healing, suppresses inflammation and improves glandular function in mouse models of Dry Eye Disease." The Ocular Surface.  24:40-50. April 2022. https://doi.org/10.1016/j.jtos.2021.12.012

Benefits of Goji Berry Consumption Against AMD

Article: Dried Goji Berries May Provide Protection Against Age-Related Vision Loss
Source: University of California, Davis
Published: January 13, 2022

Goji berries are rich in antioxidants lutein and zeaxanthin

Age-related macular degeneration (AMD) is the leading cause of vision loss in individuals 55 years of age or older. A recent randomized trial involving 27 participants found that regular consumption of goji berries (28 grams, or roughly one handful) five times per week for 90 days increased the density of macular xanthophyll pigments lutein and zeaxanthin, which protect against age-related decline in ocular health by filtering harmful light and serving as antioxidants. This was compared to participants who consumed a commercial supplement for eye health over the same time period, who did not show an increase in macular pigment density. Doctoral candidate and lead author of the study compares lutein and zeaxanthin to the "sunscreen for your eyes" and recounts her interest in studying the physiological ocular health effects of goji berries from her own cultural background. The fruit of Lycium chinense  and Lycium barbarum, two species of shrubby bushes found in northwest China, dried goji berries can be snacked on like raisins and are popular ingredients in herbal teas. Her curiosity led to the finding that the form of zeaxanthin in goji berries is a highly bioavailable form, meaning it is readily absorbed in the digestive system so the body can use it. Although dietary vitamins such as the AREDS2 formulation are recommended for people with an intermediate stage of AMD, there is currently no therapy for early stages. This pilot study is limited by its small size, and the authors hope to expand upon the research. Senior researcher of the project states, "Our study shows goji berries, which are a natural food source, can improve macular pigments of healthy participants beyond taking high-dose nutritional supplements...The next step for our research will be to examine goji berries in patients with early-stage AMD."

My rating of this study: ⭐🌸

Li X, Holt RR, Keen CL, et al. "Goji Berry Intake Increases Macular Pigment Optical Density in Healthy Adults: A Randomized Pilot Trial." Nutrients.  13(12):4409. 9 December 2021. https://doi.org/10.3390/nu13124409

The Illusion of Visual Stability in Change Blindness

Article: Like our social media feeds, our brains take a little while to update
Source: University of California, Berkeley
Published: January 12, 2022

The presence of noise accompanying visual stimuli
led to attraction to an earlier point in the video

Visual perception is like a movie that plays when our eyes are open. This movie is rich in constantly changing visual stimuli. Yet, the "continuity field," the experience that our brain merges what we see on a constant basis, is merely an illusion of visual stability. Rather than seeing the most recent image in real time, we actually see earlier versions as our brain refreshes and consolidates visual input roughly every 15 seconds. This can be influenced by the amount of noise accompanying the visual stimuli; the more noise present, the greater the lag. Senior author of the study states, "If our brains were always updating in real time, the world would be a jittery place with constant fluctuations in shadow, light and movement." In the present study, researchers looked at the mechanism behind change blindness, in which we don't notice subtle changes in time (or space). They recruited 100 participants, who were asked to view several 30-second time-lapse videos of faces morphing in age or between genders. The results showed that when asked to identify the face they saw after viewing the video, the participants almost consistently picked a frame they viewed halfway through the video (roughly 15 seconds into the video). Frames were balanced in the sense of presenting in both "ascending" and "descending" order. Additional experiments exploring longer video durations might provide further insight. Still, the study's senior author offers a plausible explanation for the observations: "It's too much work to constantly update images, so it [our brain] sticks to the past because the past is a good predictor of the present. We recycle information from the past because it's faster, more efficient and less work."

My rating of this study: ⭐🌸

Manassi M and Whitney D. "Illusion of visual stability through active perceptual serial dependence." Science Advances.  8(2). 12 January 2022. https://doi.org/10.1126/sciadv.abk2480

Super-Enhancer Vsx2 Regulates Retinal Development

Article: Modular super-enhancer controls retinal development
Source: St. Jude Children's Research Hospital
Published: January 11, 2022
Article: Super-Enhancer Oversees the Development of the Retina
Source: Genetic Engineering & Biotechnology News
Published: January 12, 2022

Enhancers are regions of DNA that do not code for proteins, but control how genes are expressed. Super-enhancers are clusters of enhancers that together regulate genes with important roles in cell identity. Scientists recently identified functions for regions of a super-enhancer, a "modular" transcription factor called Vsx2, that controls gene expression during retina formation. In particular, the Vsx2  super-enhancer has four distinct regions with different functions. This transcription factor is expressed in retinal progenitor cells and maintained in differentiated bipolar neurons and Müller glia. In animals models using wherein the gene Vsx2  is deleted (traditional knockout approaches), the eye does not form, presenting a challenge to studying the enhancer's function in detail. In the present study, the researchers wanted to understand how the Vsx2  gene is expressed in different cell types at different time points during eye development. Their functional tests of the Vsx2  super-enhancer revealed that it controls the complex and dynamic pattern of expression involved in retinal development in a modular way, with three regions playing a role in early retinal development, and another portion being important for bipolar cell genesis in later development. The authors report this being the first time researchers have demonstrated independent functions of distinct regions within a super-enhancer, which has implications for easier gene editing of individual transcription factors in different cell types at different stages of development. Finally, understanding how one super-enhancer works provides the blueprint for later study of other super-enhancers that affect other developmental processes, such as neurogenesis.

Evolutionary conservation of Vsx2 super-enhancer regions across species

My rating of this study: ⭐⭐⭐

Honnell V, Norrie JL, Patel AG, et al. "Identification of a modular super-enhancer in murine retinal development." Nature Communications.  13:253. 11 January 2022. https://doi.org/10.1038/s41467-021-27924-y

Stem Cell RPE Model for Oculocutaneous Albinism

Article: NIH researchers develop first stem cell model of albinism to study related eye conditions
Source: National Eye Institute
Published: January 11, 2022

RPE derived from OCA1A and OCA2 patients exhibits melanosome defects

Oculocutaneous albinism (OCA) is the absence of pigment in the eye, skin, and hair due to mutations to genes that produce the pigment melanin. A genetic disorder of autosomal recessive inheritance, OCA has seven types classified. Where albinism affects the eyes, there is a lack of pigment in the otherwise retinal pigmented epithelium (RPE) of the retina, as well as an underdeveloped fovea (foveal hypoplasia), the centermost part of the macula responsible for visual acuity. OCA also leads to abnormal decussation of optic nerve fibers connecting the eyes to the brain. Senior researcher of the project explains, "Animals used to study albinism are less than ideal because they lack foveae...A human stem cell model that mimics the disease is an important step forward in understanding albinism and testing potential therapies to treat it." The scientists used skin cells from people without OCA and from people with the two most common types of OCA (OCA1A and OCA2) and reprogrammed them into pluripotent stem cells (iPSCs), which were then differentiated into RPE cells. The researchers report that their RPE model "recapitulates the pigmentation defects seen in albinism, while retaining the apical-basal polarity and normal polygonal morphology of the constituent RPE cells." They plan to use the stem cell RPE model to study how lack of pigmentation affects RPE physiology and function, with particular attention to how RPE pigmentation affects fovea development. If there is a connection, they hope that improvement of RPE pigmentation, such as prenatally, could perhaps prevent or rescue visual deficits due to foveal hypoplasia. The team will next use their "disease in a dish" model for high-throughput screening of potential OCA therapies.

My rating of this study: ⭐⭐⭐

George A, Sharma R, Pfister T, et al. "In vitro disease modeling of oculocutaneous albinism type 1 and 2 using human induced pluripotent stem cell-derived retinal pigment epithelium." Stem Cell Reports.  17(1): P173-186. 11 January 2022. https://doi.org/10.1016/j.stemcr.2021.11.016

2-Photon-Excited Fluorescence SLO of the Human Eye

Article: Seeing the chemistry of vision
Source: Institute of Physical Chemistry, Polish Academy of Sciences (Poland)
Published: January 10, 2022

Two-photon-excited fluoresence of endogenous chromophores of a human retina
in three regions of interest (and with continuous wave scanning)

Advances in ophthalmic imaging modalities, such as optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO), and fundus autofluorescence (FA) have deepened our understanding of the mechanisms of eye diseases. However, some researchers argue that non-invasive assessment of metabolic processes occurring in retinal cells, such as of visual pigment regeneration, will become essential for eye diseases such as age-related macular degeneration (AMD), wherein cells in the early stage of a disease-altered retina cannot be distinguished from those of a healthy retina. Furthermore, fluorescent vitamin A derivatives, chemical intermediates of the process of light transduction, are highly sensitive to UV light, thus safe ways to analyze these markers are beyond current imaging instruments. In the present study, researchers in Poland, along with colleagues in the U.S. (at UC Irvine) developed a compact two-photon-excited fluorescence scanning laser ophthalmoscope (TPEF-SLO) and used it to spectrally resolve images of the human retina based on 2-photon excitation with near-infrared light. The instrument allowed the metabolites of vitamin A that are involved in vision, such as retinol or retinol esters, to be viewed in real time. Comparison between the eyes of two healthy human subjects and mouse models of retinal degeneration confirmed similar rapid accumulation of bisretinoid condensation products. The authors think that TPEF SLO imaging can be a noninvasive method to measure and quantify visual cycle intermediates and toxic byproducts of metabolic pathways leading to retinal degeneration. They state, "Noninvasive assessment of metabolic processes that sustain regeneration of human retinal visual pigments (visual cycle) is essential to improve ophthalmic diagnostics and to accelerate development of new treatments to counter retinal diseases...This approach opens the possibility for monitoring eye diseases in the earliest stages before structural damage to the retina occurs."

My rating of this study: ⭐⭐⭐

Boguslawski J, Palczewska G, Tomczewski S, et al. "In vivo imaging of the human eye using a two-photon excited fluorescence scanning laser ophthalmoscope." Journal of Clinical Investigation.  30 November 2021. https://doi.org/10.1172/JCI154218

Long-Term Visual Impairment in V1 of Mice after TBI

Article: Injuries to primary visual cortex cause long-term dysfunction of neural circuits
Source: Institute of Physical Chemistry, Polish Academy of Sciences (Poland)
Published: January 10, 2022

Chronic neuron loss (top),
reduced neuron firing (middle), and
disrupted visual responses (bottom)
in V1 of mice after TBI

Neuroplasticity is the remarkable ability of neural tissue to form new connections to reorganize, adapt, and self-repair. Yet, neuroplasticity, too, has its limits, as even mild head injuries can have lasting consequences for brain function at the cellular level. Traumatic brain injury (TBI) can lead to long-term visual impairment, such as loss of visual acuity or cortical blindness. In the present study, scientists examined the effects of TBI on long-term visual circuit function of adult mice to see how the neurons respond to visual stimuli two weeks and three months after mild controlled cortical impact injury to the primary visual cortex (V1). The findings show that although the primary visual cortex remained largely intact in the brain-injured mice, there was a 35% reduction in the number of neurons, with most of the affected neurons being inhibitory (rather than excitatory) neurons, and restricted to superficial layers. The researchers further report that less than half of the isolated neurons were sensitive to visual stimuli (32% at two weeks after injury and 49% at three months after injury), compared with 90% of V1 cells in the control group. Finally, there was as much as a threefold decrease in neuronal activity after the brain injury, and the cells themselves had worse spatial orientation (demonstrating impaired responses to visual stimuli and weaker size selectivity and orientation tuning). These findings reveal that even a single, mild contusion injury can produce long-lasting impairment to the way neurons encode information in the primary visual cortex.

My rating of this study: ⭐

Frankowski JC, Foik AT, Tierno A, et al. "Traumatic brain injury to primary visual cortex produces long-lasting circuit dysfunction." Communications Biology.  4:1297. 17 November 2021. https://doi.org/10.1038/s42003-021-02808-5

Spaceflight-Associated Neuro-Ocular Syndrome

Article: Living in outer space: Changes in blood flow volume may be at the heart of worsening eyesight
Source: Medical University of South Carolina
Published: January 6, 2022

Colonizing a planet beyond Earth may still be in the realm of science fiction for now; however, scientists are already studying the effects of spaceflight and living in other gravity conditions to prepare for that future, before they affect colonists on a foreign planet. Well-reported effects of outer space include bone loss, cosmic radiation, and muscle weakness. Less studied are the effects on the brain and gravity's effects on the eyes, in particular spaceflight-associated neuro-ocular syndrome (SANS). Neurology resident and first author of the paper explains that the longer astronauts stay in space, the more they’ve reported blurry vision and eyesight problems when they return to Earth. He states, "It's gotten to the point where astronauts actually carry extra pairs of glasses when they go into space...And, in fact, depending on how you define it, it affects about 70% of astronauts.” Signs of SANS include a flatten globe (consistent with a hyperopic shift in refractive error), areas of retinal injury, and optic disc swelling. Among their study cohort of 12 astronauts, the researchers found that 4 astronauts who met the diagnostic criteria for SANS had significantly greater preflight to postflight increases in intracranial dural venous volumes (in the superior sagittal sinus and both right and left transverse/sigmoid sinuses, as measured by magnetic resonance venography) than astronauts without SANS, suggesting an association between intracranial venous congestion and the development of SANS. Recovery can take weeks, months, or even years, and some astronauts never fully recover. Studying how gravity affects the brain in outer space also informs doctors about how gravity affects neurological states, such as disorders of cerebrospinal fluid circulation, here on earth. The researchers next plan to study a larger cohort of astronauts, gender differences in SANS, and to better pinpoint when the changes leading to SANS begin to develop.

Preflight and postflight venograms for an astronaut with SANS (left) and an astronaut without SANS (right)

My rating of this study: ⭐⭐

Rosenberg MJ, Coker MA, Taylor JA, et al. "Comparison of Dural Venous Sinus Volumes Before and After Flight in Astronauts With and Without Spaceflight-Associated Neuro-Ocular Syndrome." JAMA Network Open.  4(10):e2131465. 27 October 2021. https://doi.org/10.1001/jamanetworkopen.2021.31465

See also: Lower Body Negative Pressure Can Lessen Spaceflight-Associated Neuro-Ocular Syndrome

Functional MRI Combined with Perimetry to Identify Visual Field Defects in the Stroke-Damaged Brain

Article: New research gives hope for sight recovery in stroke survivors
Source: University of Nottingham (U.K.)
Published: January 6, 2022

Anatomical lesion locations for each participant

Every year 150,000 people in the U.K. have a stroke, with approximately 30% experiencing some kind of vision loss as a result. Perimetry is the gold standard for assessing residual visual field coverage; however, it has limitations such as requiring attention and cooperation from participants and only providing coarse and indirect information about the location of visual field deficits along the visual pathway. Scientists in the U.K. explored the use of functional magnetic resonance imaging (fMRI), combined with clinical perimetry, to more precisely map visual brain areas affected by vision loss in four stroke survivors (two cases of homonymous hemianopia and two cases of homonymous quadrantanopia), with the hopes that identification of such areas could provide a more complete picture of vision loss and potentially improve rehabilitation of function. Additionally, the study employed measurements from population receptive fields (pRF), lesion definitions from anatomical scans, and white matter tracts from diffusion weighted MRI data to better map the anatomy, connectivity, and function of the visual pathway after stroke. PhD student and lead author of the study explains, "A common misconception with stroke-related sight loss is that it affects vision through a particular eye. What is actually happening is that the eyes are seeing normally but the brain can’t process some of the information." The use of fMRI revealed residual activity in the visual cortex not detected by perimetry. These areas of "residual vision" are places where the brain can still process images, even if it doesn't reach awareness. The more precise mapping of fMRI also showed that the same patterns of visual field defects can result from different patterns of brain damage. Senior author of the study comments, "Using MRI to pinpoint these areas of functional vision, clinicians could work with the stroke survivor and train them to recover some function in that particular spot." The research aims to give much-needed hope to those experiencing vision loss as a devastating complication of cerebral strokes, in turn reminding us of the value of sight.

My rating of this study: ⭐🌸

Beh A, McGraw PV, Webb BS, et al. "Linking Multi-Modal MRI to Clinical Measures of Visual Field Loss After Stroke." Frontiers in Neuroscience.  5 January 2021. https://doi.org/10.3389/fnins.2021.737215

Nanoscale Architecture of the Rod Outer Segment

Article: Using cryo-electron tomography, UCI researchers reveal molecular mechanisms underlying mutations within the eye that lead to blindness
Source: University of California, Irvine, Medicine
Published: January 4, 2022



Scientists at University of California, Irvine, along with collaborators at the Max Planck Institute of Biochemistry have revealed the nanoscale molecular structure of key determinants of the mouse rod outer segment (ROS), the specialized sensory cilium of rod photoreceptor cells where phototransduction, the initial step of vision, takes place. The authors write, "A wide range of genetic aberrations have been reported to compromise ROS ultrastructure, impairing photoreceptor viability and function. Yet, the structural basis giving rise to the remarkably precise arrangement of ROS membrane stacks and the molecular mechanisms underlying genetically inherited diseases remain elusive." Although the ultrastructure of the ROS had been described in previous years, the present study utilized cryo-electron tomography (cryo-ET) and a new sample preparation method to obtain molecular resolution images of the ROS. One of the authors explains, "Cryo-ET enabled us to image rim disc structures and to quantitatively assess the connectors between disks revealing the molecular landscape in ROS, including connectors between ROS disk membranes [and] address open questions regarding the close disk stacking and the high membrane curvature at disk rims." In particular, they report, "Our data confirm the existence of two previously observed molecular connectors/spacers which likely contribute to the nanometer-scale precise stacking of the ROS disks. We further provide evidence that the extreme radius of curvature at the disk rims is enforced by a continuous supramolecular assembly composed of peripherin-2 (PRPH2) and rod outer segment membrane protein 1 (ROM1) oligomers. We suggest that together these molecular assemblies constitute the structural basis of the highly specialized ROS functional architecture." The study is especially relevant to retinal diseases such as retinitis pigmentosa and Stargardt disease that affect structural proteins. Based on the findings, they predict that new therapeutic approaches will likely emphasize gene-editing technologies over other interventions for retinal diseases.

My rating of this study: ⭐⭐⭐

Pöge M, Mahamid J, Imanishi SS, et al. "Determinants shaping the nanoscale architecture of the mouse rod outer segment." eLife.  10:e72817. 21 December 2021. https://doi.org/10.7554/eLife.72817

VR Archery Game for Orientation of Blind People

Article: Virtual reality archery is “Braille” for orientation of blind people
Source: Italian Institute of Technology (Italy)
Published: January 4, 2022

Head-pointing task in an acoustic virtual reality game

Researchers at the Italian Institute of Technology developed a virtual reality game to better understand how blind people move and orient themselves in space. Contrary to popular belief, blind people do not necessarily possess super-hearing, but instead depend on context, according to research conducted by the authors previously. In technical terms, goal-directed orientation movements in the horizontal plane during locomotion require a high degree of head-trunk coordination, which is acquired in childhood. Since early visual loss is accompanied by motor deficits, the investigators were curious about how the effect on head-trunk coordination for horizontal rotations, which had not been previously explored. In the present study involving a head-pointing task with sounds delivered in acoustic virtual reality, they report that congenital blind people struggle at coordinating head and trunk to reorient towards new targets, but still rely on their body as their main source of information via vestibular, proprioceptive and motor cues. This contrasts with blindfolded sighted people, who prefer relying on the environmental sounds. The authors state that further clarification is needed to assess the impact of blindness-related head-trunk coordination deficit on daily life activities such as steering or reaching toward targets placed sideways. Although an assessment tool at this point, they hope to develop a rehabilitation game that could help blind people become more independent, like braille does for reading and writing.

My rating of this study: ⭐

Esposito D, Bollini A, and Gori M. "Early Blindness Limits the Head-Trunk Coordination Development for Horizontal Reorientation." Frontiers in Human Neuroscience.  16 July 2021. https://doi.org/10.3389/fnhum.2021.699312

Structure of CNG Ion Channels in the Bovine Retina

Article: More insight into how vision works
Source: Paul Scherrer Institute (Switzerland)
Published: January 3, 2022

Light transduction in the rod photoreceptors of the retina occur by way of cyclic nucleotide-gated (CNG) ion channels, a gatekeeper ion channel that controls whether specific particles are allowed through the cell membrane into the interior of the receptor cell. In darkness, the ion channel is open, while in light the ion channel is triggered to close through a cascade of events. However, if the ion channel is not closed completely, the photoreceptor fails to prevent positively charged ions (such as calcium ions) from entering the cell, which in turn disrupts both the cell's electrochemical balance and the propagation of the hyperpolarization signal from the eye to the brain. In the present study, the researchers extracted the channel proteins from bovine eyes, a complex process that took two years to obtain enough protein to work with. The team then used cryo-electron microscopy to reveal the three-dimensional structure of the ion channel. PhD student and first author of the study explains, "In contrast to previous studies on the structure of the ion channel, we investigated the native protein as it exists in the eye. We are therefore much closer to the real conditions that exist in living creatures." The microscopy revealed that the protein comprises four parts: three lots of subunit A, and one lot of subunit B, the exact combination of which is needed for proper functioning. The B subunit in particular seems to play an especially important role in that a side arm of the protein (a single amino acid) protrudes from the rest of the protein, like a barrier across a gateway, narrowing the passageway to prevent ions from passing through the channel. This finding is novel and additional to narrow areas in the A subunit, which had been previously thought to be the only ones. The authors hope that study of the structure of cyclic nucleotide-gated ion channels will guide the search for molecules that could influence the channel to close completely, thereby preventing photoreceptor degeneration in diseases such as retinitis pigmentosa.

Merged particles after 2D classification (N = 165062)

My rating of this study: ⭐⭐

Barret DCA, Schertler GFX, Kaupp UB, et al. "The structure of the native CNGA1/CNGB1 CNG channel from bovine retinal rods." Nature Structural & Molecular Biology.  30 December 2021. https://doi.org/10.1038/s41594-021-00700-8