Week in Review: Number 22

CIB2 Regulates mTORC1 in Photoreceptor Autophagy
Researchers studying the pathology of age-related macular degeneration (AMD) are looking into two proteins that play a role in photoreceptor autophagy, a process that is essential for proper light detection. Without this clean up by support cells, the undigested photoreceptor material accumulates over time, contributing to a toxic environment that eventually leads to retinal degeneration and potential vision loss. One protein called calcium and integrin binding protein 2 (CIB2) seems to be responsible for this photoreceptor maintenance; eyes of mice engineered without the CIB2 gene exhibited sub-retinal pigment epithelium (RPE) deposits, marked accumulation of drusen markers, reduced lysosomal capacity and autophagic clearance, and impaired visual function. The researchers also investigated the role of a protein called mTORC1. Involved in other human diseases such as cancer, obesity, and epilepsy, mTORC1 plays a regulatory role in processes such as cleaning up cellular debris. They found that mTORC1 was overactive in mice with CIB2 mutation and also overactive in human eye tissue samples from people with dry AMD. The mTOR protein comes in two varieties: mTORC1 and mTORC2. Because mTOR is involved in many other cellular processes, tinkering with it leads to major side effects. The researchers think regulating mTORC1 via CIB2 can bypass many of these adverse effects. One of the authors says, “Using the evolving understanding of the mechanistic role of mTORC1, this study has provided great insights into new ways that researchers can begin to find ways to preserve, to treat, and/or improve macular degeneration, and thus improve the quality of life and independent living in many older adults.”

Selective Threshold Modulation by Inhibitory Neurons Increases Information Transmission
Researchers at the Salk Institute explored modulation of neuronal thresholds via inhibitory neurons, testing their theory with cells in the retina. Although ubiquitous in the brain, threshold modulation also reduces the strength of the original signal, prompting the question as to why such a dampening effect is so widespread. The researchers found that the decrease in information transmission can be nearly completely eliminated if modulation by inhibitory neurons is applied selectively to the most sparsely responding neurons (i.e., neurons with the lowest spike rate) in a circuit or group of neurons. The authors provide a mathematical (but intuitive) explanation for this outcome relating to the curve of the information function of a single neuron with respect to its threshold. As they explain in the paper, "This function is concave for small thresholds and convex for large thresholds. This is important because concave functions decrease their value upon averaging of their inputs, as occurs as a result of threshold modulation, while convex functions increase their value. This means that neurons with small thresholds, i.e., high spike rates, will suffer a decrease in information transmission upon modulation. In contrast, neurons with large thresholds, i.e., small spike rates, will increase information transmission upon threshold modulation." Therefore, neurons with the smallest spike rates will experience the greatest increase in information transmission upon threshold modulation. The researchers tested their predictions on retinal (sustained Off-type) amacrine cells modulating pairs of ganglion cells, termed "adapting" and "sensitizing," with "the main differences between these cell types are that adapting cells have higher thresholds and larger noise levels than sensitizing cells." They found that the amacrine cells exert a stronger effect on the threshold of adapting ganglion cells than on the threshold of sensitizing ganglion cells. The exploratory techniques involve intracellular current injection of the neurons, which is far from clinical applications. Nonetheless, these findings at the cellular level are relevant in providing knowledge in foundational science that could inform later clinical treatments.

U.K. Research Project Aims to Validate the OHTS-EGPS Glaucoma Risk Calculator
A research team in the U.K. will begin a two-year project launched in June 2021 to improve upon ways to monitor ocular hypertension (elevated intraocular pressure) as a risk factor for developing glaucoma, which could lead to vision loss if not detected and treated early. Eye pressure is considered high if it is above 21 mmHg, although there is debate as to whether and how to treat individuals with eye pressures in the low and mid-20s. Benefit from treatment with pressure-lowering eye drops are weighed against adverse effects, cost, and inconvenience given a lifetime commitment to daily use of medications. An alternative first-line therapy is selective laser trabeculoplasty (SLT), although this option is not effective on all patients. Thus, having a tool to assess risk of progression from ocular hypertension to glaucoma, which is defined by irreversible damage to the optic nerve (and other ocular structures), would support decision-making for both clinicians and patients. A glaucoma risk calculator called OHTS-EGPS is available that makes use of data from the Ocular Hypertension Treatment Study and the European Glaucoma Prevention Study clinical trials. However, the U.K. researchers state that this risk calculator has not been tested on U.K. patients. Their project aims to validate the OHTS-EGPS for use within the U.K. health care system through review of anonymised NHS electronic medical records of over 23,000 people who have ocular hypertension. More specific goals of the project include investigating the value of treatment in people with ocular hypertension of 22 or 23 mmHg and validating the tool for different follow-up intervals of patients according to their glaucoma risk. Ultimately, the project seeks to "both optimise the management of people with ocular hypertension and reduce costs related to the management of the condition."

Visual Backward Masking in Young Infants
Visual perception begins in the retina and is serially processed in increasingly higher levels of the visual cortex in a bottom-up manner. However, top-down feedback is also sent from higher to lower visual areas. Researchers in Japan interested in the interference of this feedback processing in the brain studied visual backward masking in infants ages 3 to 8 months. Visual backward masking occurs when the perception of a second object masks the perception of an immediately preceding object. This phenomenon occurs even if the second object does not spatially overlap the first object, such as a contour or four dots surrounding the object in the present experiments. To test visual perception in infants, the researchers presented them with images of faces on a computer screen and measured the time they spent looking at the images, taking into account that infants look longer at faces (compared to other images). The faces were presented in two conditions: followed by a mask image and followed by nothing. They discovered that infants ages 7 to 8 months, similar to adults, could not see the faces if followed by a mask image, indicating that backward masking had occurred. In contrast, infants ages 3 to 6 months could perceive the faces even if they were followed by the mask. This indicates that visual backward masking did not occur, suggesting that feedback processing is immature in the brains of infants younger than 7 months of age. The study's first author explains, "[Y]ounger infants do not have feedback processing that backward masking should interfere, and thus, masking is ineffective for them." In the latter half of their first year of life, top-down processing begins to take effect to provide that feedback, which becomes important in robustly perceiving ambiguous visual input. As another author proffers, "In return for susceptibility to visual masking, we acquire the ability to robustly perceive ambiguous visual scenes."

Small Study Investigated the Effect of Pure Cocoa Ingestion on Photopic Visual Acuity
Researchers in Spain explored the effect of two dietary polyphenols—cocoa flavanols and red berry anthocyanins—on visual acuity and cone-mediated dark adaptation in healthy eyes. The study involved 37 healthy volunteers who drank a glass of milk with 2.5 grams of pure cocoa, 10 grams of freeze-dried berry powder, or just milk (control) on three separate visits. Interestingly, this study explored the effect of these polyphenols in acute doses, as compared to longer term dietary routines. Levels of polyphenols in their urine were measured after three hours. Visual acuity was tested in both photopic ("daylight") and mesopic (low light) conditions. Tests of dark adaptation were also performed. Results of the study showed improvement in photopic visual acuity in the group that ingested pure cocoa. This effect was not seen in mesopic conditions with either cocoa or red berry ingestion, and the trend toward improvement in photopic conditions with red berry ingestion was not statistically significant. The investigators hypothesized that the flavanols and theobromine, both alkaloids that stimulate the central nervous system and found in cocoa, increase visual acuity by improving attention or processing of visual information. The authors emphasized that questionnaires and eye examinations were conducted to demonstrate the absence of dietary factors or prior pathology that could influence the analysis of results. However, they also acknowledged that the effect of caffeine, which is also present in pure cocoa, is unknown and could also contribute to the results. Overall, studies into diet potentially have many confounding variables, and a small sample size limits how far results can be extrapolated. The authors conclude, "This work highlights the need for new research that delves deeper into the effect of flavanols, anthocyanins and methylxanthines on visual acuity and attention, both in acute and chronic interventions."

In Other News
(1) Children prioritize hearing over vision given emotionally incongruent input
(2) Art: Sculptural installation explores color and light
(3) Time compression in virtual reality (Related)