Week in Review: Number 41

Campana Cell: a New Type of Neuron in the Retina
Scientists at Moran Eye Center at University of Utah have discovered a new type of neuron in the retina. Named the Campana cell for its bell-like shape, this interneuron possesses hybrid characteristics of both a bipolar cell and an amacrine cell, while also differing significantly from both the other types of interneurons. For example, like bipolar cells, Campana cells relay information from the photorceptors (in this case both rods and cones) to the retinal ganglion cells. Campana cells also share some features with amacrine cells, specifically Aii-ACs, such as neurite morphology in the inner plexiform layer, the expression of some AC-specific markers, and possibly the release of the inhibitory neurotransmitter glycine. However, this combination of characteristics also makes the Campana cell distinct. The lead researcher states, “Based on its morphology, physiology, and genetic properties, this cell doesn’t fit into the five classes of retinal neurons first identified more than 100 years ago. We propose they might belong to a new retinal neuron class by themselves.” Thus far, the scientists have discovered that Campana cells remain activated for an unusually long duration, as long as 30 seconds in response to a 10 millisecond light flash stimulus. The lead scientist speculates that this long duration of activation plays a role in encoding memory, similar to persistently firing neurons in the brain. The researchers conclude, "[O]ur results open the possibility for an unconventional retinal cell class that plays unique roles in visual processing."

Carbon Monoxide Explored as an Ingestable Drug Therapy for Diabetic Retinopathy
Researchers are investigating the potential of small amounts of ingested carbon monoxide to reduce oxidative stress and inflammation, both precursors to retinal diseases like diabetic retinopathy. The compound, called HBI-002, is currently in early-stage clinical trials for sickle cell disease. Although we don't often consider carbon monoxide as occurring in our bodies, tiny amounts of carbon monoxide are actually produced endogenously by own cells and tissues as an antioxidant against oxidative stress and inflammation. For example, the enzyme heme oxygenase 1, a component of hemoglobin and immune cells, releases carbon monoxide (at an amount 1,000 times lower than what we inhale from the air) to reduce oxidative stress and inflammation as part of these cells' function, naturally upregulating the enzyme when there is tissue damage. Disease states such as diabetes disturb these natural mechanisms, thereby creating environments that are more prone to oxidative stress and inflammation. So "we have to think of ways to enhance, or reestablish, those mechanisms that would normally protect us," one of the principal investigators explains. The research team has been awarded a grant to further explore HBI-002’s potential. They plan to look at how the compound works in both an ischemic model of diabetic retinopathy and a model with more natural disease progression, with the hope of finding a noninvasive therapy for diabetic retinopathy.

Preliminary tests indicate that HBI-002 can "make the trip" in oral form all the way to the retina. The carbon monoxide is ingested as a liquid and becomes the more familiar gaseous state in the intestines, a unique liquid to gas transformation. There, it naturally binds to hemoglobin and travels along blood vessels to the retina. The researchers note that HBI-002 has no trouble finding hemoglobin; in fact, it is carbon monoxide's strong affinity for hemoglobin, blocking oxygen from binding, that causes its potentially fatal effects in high amounts. Once in the cells of the retina, the carbon monoxide finds heme oxygenase 1 and helps to induce the steps that yield its antioxidant, anti-inflammatory effects. If the benefits of HBI-002 continue to hold, the researchers then plan on further studying its mechanism of action, as well as optimal dosing and frequency for the compound. The retina a part of the body that has been thus far been difficult for oral (and topical) drugs to safely target, that is, without systemic and local adverse effects. The development of a safe, ingestable treatment for diabetic retinopathy could significantly relieve the burden of invasive therapies, as well as have implications for broader applications for vascular diseases in general.

Pupils Respond to Differing Perceived Quantities
Although luminance is the main determinant of pupil size, other factors can also affect pupillary response. These include automatic responses to emotions and cognitive engagement. Scientists in Australia, with colleagues in Italy, were interested in studying whether pupils also have a physiological response to stimulus appearance and attention, that is, whether perceived numerosity modulates the pupillary light response. The study recruited 16 volunteers with normal vision who participated in a pupillometry experiment, 14 of whom participated in a numerosity discrimination experiment, and 13 of whom participated in a second pupillometry and psychophysics experiment. The perception aspects of the experiments involved tasks such as passively observing visual stimuli (black or white dots) of matched luminance but differed in their level of connectedness, whether separated dots or joined by a line, which has the illusory effect of decreasing the total number of perceived objects. The researchers also tested whether varying the relative size of the dots and the thickness of the line had any effect. The authors report, "Constriction to white arrays and dilation to black were stronger for patterns with higher perceived numerosity, either physical or illusory, with the strength of the pupillary light response scaling with the perceived numerosity of the arrays. Our results show that even without an explicit task, numerosity modulates a simple automatic reflex, suggesting that numerosity is a spontaneously encoded visual feature." One of the researchers adds that the spontaneous ability to perceive quantity, an innate "number sense," is shared among most species, with evolutionary implications such as in the perception food items or of predators.

Sinusoidal Mapping Pattern Found in V2 of the Visual Cortex of Tree Shrews
Similar to mapping the cartography of geographic space, neuroscientists who study vision map how our brain represents and makes sense of the world we see. One organizing property of the visual cortex is known as retinotopic mapping, wherein the spatial arrangement of neurons from the retina, via the optic nerve, is preserved in their spatial arrangement on the visual cortex. The prevailing theory is that the primary visual cortex (V1) follows a simple, linear pattern of roughly identical mapping of visual space represented on the cortex. However, hints of discrepancies in some studies prompted the researchers to wonder if additional patterns exist in the brain. Using a combination of single-cell functional imaging, computational modeling and connectivity studies, they uncovered such a pattern for the first time in area V2 of the tree shrew, an animal model that is amenable to research tools developed in mice (including both having a smooth brain), but is a closer relative to primates. Specifically, the researchers report that mapping of an object’s elevation, how high or low it is, followed closely with the smooth linear map found in V1, but mapping the azimuth, its horizontal position left or right of center, revealed a dramatically different sinusoidal, or oscillating pattern. One difference is that V1 is a "square" region while V2 has a thin, elongated shape. Using colored dyes to trace the connection between the two regions  confirmed that neuronal projections from V1 perfectly aligned with the sinusoidal map in V2. Furthermore, the researchers discovered that neuronal preference for certain visual features is tied directly to the retinotopic map of visual space, illustrating that the sensitivity that neurons have to particular features can vary depending on its location in visual space, that is, not only what but also where. Senior author of the study states, “Our findings open the door to a different way of thinking about how cortical circuits are organized, how they contribute to visual perception, and ultimately, behavior.”

Designing Enhanced Cinematic Experiences for Visually Impaired Audiences
In 2016, film-makers in the U.K. conducted a survey which found that 34% of visually impaired people surveyed had not attended the cinema in the previous 12 months, compared to only 5.5% of sighted people surveyed. The participants who were visually impaired reported issues of accessibility discouraging them from attending. These researchers subsequently sought to improve up on the traditional Audio Description, a third-person commentary added onto film soundtracks for visually impaired film and television audiences, to create a more inclusive film-watching experience. The Enhanced Audio Description (EAD) they developed utilizes three main techniques that focus on sound design: (1) the addition of sound effects to provide more cinematographic information about the film, such as providing information about actions, establishing shots, conveying abstract scenes, and indicating the presence of characters, time, and place; (2) the use of 3D audio over headphones to convey the position of characters and objects portrayed on the screen, and (3) the use of first-person narration to portray aspects of the story that cannot be conveyed through sound effects, e.g., feelings, gestures, and colors. This alternative soundtrack overall intended to minimize the number of verbal descriptions to avoid them masking crucial elements in the original soundtrack. They tested their EAD on a case study short film called "Pearl" thus far. They argue that the integrated approach produces an organic form of accessibility that can cater to both sighted and visually impaired audiences to promote more inclusive cinematic experiences, and can be offered alongside traditional AD for difference audience preferences. First author of the study comments, “We have sought to create a new paradigm for accessibility to film and television by shifting the focus from verbal descriptions to the power of creative sound design and the importance of incorporating accessibility to the creative filmmaking workflows. By designing such works, sound can be a vehicle for social inclusion by making cinematic experiences shared accessible experiences.”

In Other News
(1) Clinical trial of topical anti-VEGF (EXN 407) for retinal neovascular diseases
(2) U.K. launched first eye clinic for people with Down's syndrome
(3) Colorblind fish reveal the evolution of vision
(4) Eyes reveal the life history of fish