Week in Review: Number 44

Genetics of Iris Cell Types & Study of Iris Cell Origins
The iris provides the aperture with which we control varying levels of light that reaches our retina. The iris also plays a role in a variety of eye conditions that affect inflammation, intraocular pressure, neurological assessment, etc. Researchers at Johns Hopkins wanted to further understanding of the iris through genetically mapping the different cell types of the mouse iris, tracking how gene expression affects iris musculature during constriction and dilation, and defining the developmental origins of iris cells. Single-cell RNA sequencing revealed four new types of cells in the iris: two types of iris stromal (structural) cells and two types of iris smooth muscle (sphincter) cells that enable constriction in response to light. Because iris muscle contraction is a relatively drastic physical change for such a delicate structure, the researchers wondered if changes in gene expression were involved. Genetic analysis showed that while there was not much change in gene expression between a relaxed mouse eye and a constricted one, there were dramatic differences in the genes expressed in the dilated mouse eye (specifically a gene called EGR1 in dilator muscle cells), when the iris tissue is most compressed. EGR1 is a gene that responds to changes in the cellular environment throughout the body, leading the researchers to hypothesize that it is upregulated in response to the physical stress. Finally, the researchers used a genetically engineered mouse model to follow the embryonic development of the neural crest. They report, "The majority of the iris cells came from the neural crest, which gives us a fundamental understanding of how the iris develops." They hope that the information will connect genetic similarities between the mouse and human eye, and offer clues to develop new diagnostic tests and treatments for diseases that affect the iris, such as anterior uveitis and aniridia, as well as aid in regenerative medicine for disorders of the eye.

Columnar Processing & Feedback in Border Ownership in V4 of the Macaque Visual Cortex
To interpret a visual scene, the brain must differentiate object from background. It does so by deciphering borders. Neuroscientists at the Salk Institute are studying how neurons assign border ownership. Individual neurons in the brain's visual cortex only receive information about a minuscule region of a scene. As such, neurons that receive information at the border of objects do not have information about the overall context of the scene. Yet, researchers have discovered sets of neurons that specifically signal border ownership, that is, which side of the border belongs to the object. Some scientists have hypothesized a feedforward mechanism, wherein successively more complex computations are added as visual information travels from the retina into increasingly higher-order areas of the brain, until the brain builds an overall interpretation of the visual scene. Other scientists emphasize the importance of feedback mechanisms, in which downstream areas of the brain process some of the information before sending clues to upstream brain areas to facilitate deciphering borders. The present study sought to determine which hypothesis was correct.

The researchers used multielectrode probes to investigate different layers of area V4 of the macaque visual cortex as the monkeys views squares on blank backgrounds. The authors report, "We find that border ownership selectivity occurs first in deep layer units," which lends evidence to feedback pathways being involved. They also observed a columnar selectivity for borders, such that neurons stacked in the same vertical penetration (by the probe), through multiple horizontal layers, shared the same border ownership preference. Some columns preferred scenes where the left side of the border was the object and other columns preferred scenes where the right side was the border of the the object, suggesting a systematic organization. The authors conclude, "Together our data reveal a columnar organization of border ownership in V4 where the earliest border ownership signals are not simply inherited from upstream areas, but computed by neurons in deep layers, and may thus be part of signals fed back to upstream cortical areas or the oculomotor system early after stimulus onset." They next plan to investigate how information conveyed by feedback contributes to the processing of borders, perhaps aiding in brain disorders where perception is distorted.

Low Contrast-Preferring Neurons in V1 Maintain Perception of Familiar Objects
The appearance of objects can change in different lighting conditions, such as decreases to contrast in dim lighting or foggy weather. Yet, the brain perceives the object as the same object even when its features become less distinct. Researchers in Japan sought to investigate the mechanism behind the visual system's flexible representation of information, specifically how it maintains perception of low-contrast familiar objects. The prevailing thought is that the primary visual cortex (V1) processes visual information as a direct reflection of the strength of external stimuli; as such, high-contrast stimuli elicit stronger responses, and vice versa for low-contrast stimuli. In the present study, the scientists discovered that a number of neurons in V1 of the mouse visual cortex preferentially respond to low-contrast stimuli after repeated experience, such that low-contrast stimuli elicit stronger responses and high-contrast stimuli elicit weaker responses. The activity of these low contrast-preferring neurons fired more frequently in correct-choice than incorrect-choice trials, and were rare during passive viewing without training, demonstrating the influence of experience in strengthening the neural connections. A change in neuronal excitation-inhibition balance might also play a role. One of the authors states, "This flexible information representation may enable a consistent perception of familiar objects with any contrast." They suggest that artificial neural networks could better model vision by incorporating not only high contrast-preferring neurons but also low contrast-preferring neurons to improve discrimination of visual stimuli.

Preliminary Review Aims to Examine the Molecular Benefits of Exercise on Retinal Health
The health benefits of exercise are myriad and well-recognized. However, the benefits of exercise at a molecular level have not been studied in detail, especially in the context of the central nervous system and its extension to the retina, in turn representing the connection between exercise and eye health. Researchers in Australia are investigating the molecular signals sent from the skeletal muscles of the body to the brain, and the eyes, immediately after we exercise. They hope that understanding these molecular messages could help inform the creation of supplements, similar to vitamins, for patients who are incapable of physical activity, whether due to injury or age-related decline in physical movement. The authors report a preliminary review encompassing topics such as "oxidative stress and mitochondrial health; inflammation; protein aggregation; neuronal health; and tissue crosstalk via extracellular vesicles," with an emphasis on "decipher the molecular benefits of exercise in retinal health and disease." Although "prescribing" exercise has been beneficial in neurological diseases such as Alzheimer's and Parkinson's, the researchers emphasize that the effects have been understudied as they apply to retinal health and disease, such as age-related macular degeneration (AMD). Importantly, they note that should such a futuristic therapy one day be developed, it would not be intended for the general public, but rather for patients who have restricted movement rendering them unable to exercise. First author of the paper remarks, "We can't possibly package all the effects of exercise into a single pill, there are too many benefits that stretch throughout the entire body beyond what we could 'prescribe' and that's not the goal."

Caffeine Consumption and Dynamic Visual Acuity
Widespread testimony supports the acute stimulating effect of caffeine consumption. Researchers in Canada conducted the first study to examine the effect of caffeine ingestion on dynamic visual acuity (DVA). They argue in favor of dynamic vision testing in the sense that "[t]esting visual acuity under dynamic conditions can provide more information about our functional performance in these [everyday] scenarios than traditional static visual acuity measurements alone." Since most of the objects we interact with in our environment are moving, dynamic visual acuity skills are especially important in daily activities. The study recruited 21 low-caffeine consumers aged early to mid-twenties to take part in a placebo-controlled, double-blind, and balanced crossover study. On two separate days, participants were divided into two groups, ingesting a capsule containing either caffeine (4 mg/kg) or a placebo; DVA was measured before and 60 minutes after ingestion. The researchers found that caffeine ingestion improved the accuracy of both horizontal and random motion paths of DVA. However, while caffeine ingestion was associated with faster reaction time for horizontal moving targets, it had no effect on improving reaction time for randomly moving targets. They infer that caffeine has an ergogenic effect to positively influence participants' stimulus processing. One of the authors remarks, "Our findings show that caffeine consumption can actually be helpful for a person’s visual function by enhancing alertness and feelings of wakefulness. This is especially true for those critical, everyday tasks, like driving, riding a bike or playing sports, that require us to attend to detailed information in moving objects when making decisions."

In Other News
(1) How the brain paints the beauty of a landscape
(2) Environment and culture shape color lexicon and color perception
(3) CORE names “Top 10 of 2021” scientific papers for the eye care community