Posts Tagged ‘retina’


Before light reaches these rods and cones in the retina, it passes through some specialized cells that send signals to brain areas that affect whether you feel happy or sad.

by Jon Hamilton

Just in time for the winter solstice, scientists may have figured out how short days can lead to dark moods.

Two recent studies suggest the culprit is a brain circuit that connects special light-sensing cells in the retina with brain areas that affect whether you are happy or sad.

When these cells detect shorter days, they appear to use this pathway to send signals to the brain that can make a person feel glum or even depressed.

“It’s very likely that things like seasonal affective disorder involve this pathway,” says Jerome Sanes, a professor of neuroscience at Brown University.

Sanes was part of a team that found evidence of the brain circuit in people. The scientists presented their research in November at the Society for Neuroscience meeting. The work hasn’t been published in a peer-reviewed journal yet, but the researchers plan to submit it.

A few weeks earlier, a different team published a study suggesting a very similar circuit in mice.

Together, the studies offer a strong argument that seasonal mood changes, which affect about 1 in 5 people, have a biological cause. The research also adds to the evidence that support light therapy as an appropriate treatment.

“Now you have a circuit that you know your eye is influencing your brain to affect mood,” says Samer Hattar, an author of the mouse study and chief of the section on light and circadian rhythms at the National Institute of Mental Health. The finding is the result of a decades-long effort to understand the elusive link between light and mood. “It is the last piece of the puzzle,” Hattar says.

The research effort began in the early 2000s, when Hattar and David Berson, a professor of neuroscience at Brown University, were studying cells in the retina.

At the time, most scientists thought that when light struck the retina, only two kinds of cells responded: rods and cones. But Hattar and Berson thought there were other light-sensitive cells that hadn’t been identified.

“People used to laugh at us if we say there are other photoreceptors distinct from rods and cones in the retina,” Hattar says.

The skeptics stopped laughing when the team discovered a third kind of photoreceptor that contained a light-sensitive substance called melanopsin not found in rods and cones. (The full name of these cells, if you’re interested, is intrinsically photosensitive retinal ganglion cells, or ipRGCs.) These receptors responded to light but weren’t part of the visual system.

Instead, their most obvious function was keeping the brain’s internal clock in sync with changes in daylight. And many scientists assumed that this circadian function also explained seasonal depression.

“People thought that the only reason you get mood problems is because your clock is misaligned,” Hattar says.

Other potential explanations included speculation that reduced sunlight was triggering depression by changing levels of serotonin, which can affect mood, or melatonin, which plays a role in sleep patterns and mood. But the evidence for either of these possibilities has been weak.

Hattar and Berson were pretty sure there was a better reason. And, after years of searching, they found one.

In September, Hattar’s team published a study about mice suggesting a direct pathway between the third kind of photoreceptor in the retina and brain areas that affect mood.

When these cells were present, an artificially shortened cycle of light and dark caused a version of depression in a mouse. But when the team removed the cells with gene-editing tools, the mouse didn’t become depressed.

Sanes knew about the research, in part because he and Berson are neuroscientists at Brown. And he was so intrigued by the discovery of the new pathway between retina and brain in mice that he decided to see whether something similar was going on in human brains.

Sanes’ team put young adults in an MRI machine and measured their brain activity as they were exposed to different levels of light. This allowed the team to identify brain areas that seemed to be receiving signals from the photoreceptors Hattar and Berson had discovered.

Two of these areas were in the front of the brain. “It’s interesting because these areas seem to be the areas that have been shown in many studies to be involved in depression and other affective disorders,” Sanes says.

The areas also appeared to be part of the same circuit found in mice.

The finding needs to be confirmed. But Hattar is pretty confident that this circuit explains the link between light exposure and mood.

So now he’s trying to answer a new question: Why would evolution produce a brain that works this way?

“You will understand why you would need light to see,” he says, “but why do you need light to make you happy?”

Hattar hopes to find out. In the meantime, he has some advice for people who are feeling low: “Try to take your lunch outside. That will help you adjust your mood.”

https://www.npr.org/sections/health-shots/2018/12/21/678342879/scientists-find-a-brain-circuit-that-could-explain-seasonal-depression

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by Judy George

Retinal thinning was linked to dopaminergic neuronal atrophy in a cross-sectional analysis, raising the possibility that it could be a way to detect pathologic changes in early Parkinson’s disease (PD) patients, researchers said.

Drug-naïve patients with early Parkinson’s showed retinal thinning as measured by optical coherence tomography (OCT) that correlated with both disease severity and nigral dopaminergic degeneration, reported Jee-Young Lee, MD, PhD, of the Seoul National University Boramae Medical Center, and colleagues in Neurology.

“Our study is the first to show a link between the thinning of the retina and a known sign of the progression of the disease — the loss of brain cells that produce dopamine,” Lee said in a statement.

“We also found the thinner the retina, the greater the severity of disease. These discoveries may mean that neurologists may eventually be able to use a simple eye scan to detect Parkinson’s disease in its earliest stages, before problems with movement begin.”

Retinal pathology has been tied to other neurodegenerative disorders including dementia. In previous studies, retinal nerve fiber layer thickness has been linked to Parkinson’s disease, and OCT is a potential PD biomarker.

The search for a definitive Parkinson’s biomarker has been extensive and includes clinical (anosmia; REM behavior disorder), genetic (GBA mutation; LRRK2 mutation), and biochemical (blood and cerebrospinal fluid) techniques, along with positron emission tomography (PET), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT) imaging.

No biomarker has been validated for clinical practice, noted Jamie Adams, MD, of the University of Rochester Medical Center in New York, and Chiara La Morgia, MD, PhD, of the University of Bologna in Italy, in an accompanying editorial: “Because of the complexity of the disease, combining biomarkers from different categories is likely the best strategy to accurately predict PD status and progression.”

In this analysis, Lee and colleagues studied 49 Parkinson’s patients with an average age of 69, along with 54 age-matched controls, including only early-stage, drug-naïve PD patients without ophthalmologic disease.

The researchers used high-resolution OCT to measure retinal nerve fiber layer thickness, microperimetry to measure retinal function, and dopamine transporter analysis to measure N(3-[18F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane uptake in the basal ganglia. Retinal layer thickness and volume were measured and compared in PD patients and controls.

Retinal thinning was found in the inferior and temporal perifoveal sectors of the PD patients, particularly the inner plexiform and ganglion cell layers, along with an association between retinal thinning and dopaminergic loss in the left substantia nigra. The team also reported an inverse association between inner retinal thickness in the inferior perifoveal sector and disease severity (Hoehn and Yahr stage), and a positive correlation between macular sensitivity and retinal layer thickness.

“Overall, these data support the presence of an association between retinal thinning and dopaminergic loss in PD,” said Adams and La Morgia. “Inner retinal thinning in individuals with PD has been reported in previous studies, but this is the first study that demonstrates a correlation between inner retinal thinning and nigral dopaminergic loss.”

“These findings may point to a pathologic connection between the retina and basal ganglia in PD and are in line with previous studies reporting asymmetric retinal nerve fiber layer loss, more evident in the eye contralateral to the most affected body side.”

The results need to be interpreted with caution, Lee and co-authors noted. Retina analysis was limited to the macular area in this research. Studies with larger numbers of Parkinson’s patients are needed to confirm the findings. And this study was a cross-sectional analysis, so correlations between retinal changes and PD severity need to be established over time.

But if the findings are confirmed, “retina scans may not only allow earlier treatment of Parkinson’s disease, but more precise monitoring of treatments that could slow progression of the disease as well,” Lee said.

https://www.medpagetoday.com/neurology/parkinsonsdisease/74575


Age-related macular degeneration, diabetic retinopathy and glaucoma were all associated with a higher risk of developing Alzheimer’s disease in a new study.

by Rich Haridy

A new study has found an interesting correlation between several degenerative eye diseases and the onset of Alzheimer’s disease. No mechanism explaining the connection has been proposed at this stage but it is thought these eye conditions may help physicians identify patients at risk of developing Alzheimer’s at a stage before major symptoms appear.

The five-year study followed almost 4,000 patients over the age of 65, all without clinically diagnosed Alzheimer’s disease at the time of enrolment. After five years, 792 subjects were officially diagnosed with Alzheimer’s. The study found that those subjects with age-related macular degeneration, diabetic retinopathy or glaucoma, were 40 to 50 percent more likely to develop Alzheimer’s compared to patients without those specific conditions. No correlation between cataracts and an increased risk of Alzheimer’s were found.

“We don’t mean people with these eye conditions will get Alzheimer’s disease,” cautions Cecilia Lee, lead researcher on the study. “The main message from this study is that ophthalmologists should be more aware of the risks of developing dementia for people with these eye conditions and primary care doctors seeing patients with these eye conditions might be more careful on checking on possible dementia or memory loss.”

The researchers are clear that there are no definable causal connections between these eye conditions and Alzheimer’s at this stage, but the study does highlight the potential of using the eye as a way to better understand what is going on in the brain. Intriguingly, this isn’t the first bit of research that has found correlations between signs detected in the eye and the onset of Alzheimer’s disease.

Last year, a team from Cedars-Sinai Medical Center revealed that the same type of amyloid protein deposits found in the brain, and hypothesized as a major pathogenic cause of Alzheimer’s, can also be detected on the retina. That research suggested a possible investigational eye scan could become an effective early screening device for the disease.

While this new study does not at all cross over with last year’s research, and there is no implication that amyloid proteins play a part in these degenerative eye diseases, it does add to a fascinating growing body of work that highlights the eye’s role in helping offer a deeper insight into the cognitive health of our brain.

The research was published in the journal Alzheimer’s & Dementia.

https://newatlas.com/eye-disease-alzheimers-connection/55823/


An array of semitransparent organic pixels on top of a ultrathin sheet of gold. The thickness of both the organic islands and the underlying gold is more than one-hundred times thinner than a single neuron.

SUMMARY: A simple retinal prosthesis is under development. Fabricated using cheap and widely-available organic pigments used in printing inks and cosmetics, it consists of tiny pixels like a digital camera sensor on a nanometric scale. Researchers hope that it can restore sight to blind people.

Researchers led by Eric Glowacki, principal investigator of the organic nanocrystals subgroup in the Laboratory of Organic Electronics, Linköping University, have developed a tiny, simple photoactive film that converts light impulses into electrical signals. These signals in turn stimulate neurons (nerve cells). The research group has chosen to focus on a particularly pressing application, artificial retinas that may in the future restore sight to blind people. The Swedish team, specializing in nanomaterials and electronic devices, worked together with researchers in Israel, Italy and Austria to optimise the technology. Experiments in vision restoration were carried out by the group of Yael Hanein at Tel Aviv University in Israel. Yael Hanein’s group is a world-leader in the interface between electronics and the nervous system.

The results have recently been published in the scientific journal Advanced Materials.

The retina consists of several thin layers of cells. Light-sensitive neurons in the back of the eye convert incident light to electric signals, while other cells process the nerve impulses and transmit them onwards along the optic nerve to an area of the brain known as the “visual cortex.” An artificial retina may be surgically implanted into the eye if a person’s sight has been lost as a consequence of the light-sensitive cells becoming degraded, thus failing to convert light into electric pulses.

The artificial retina consists of a thin circular film of photoactive material, and is similar to an individual pixel in a digital camera sensor. Each pixel is truly microscopic — it is about 100 times thinner than a single cell and has a diameter smaller than the diameter of a human hair. It consists of a pigment of semi-conducting nanocrystals. Such pigments are cheap and non-toxic, and are commonly used in commercial cosmetics and tattooing ink.

“We have optimised the photoactive film for near-infrared light, since biological tissues, such as bone, blood and skin, are most transparent at these wavelengths. This raises the possibility of other applications in humans in the future,” says Eric Glowacki.

He describes the artificial retina as a microscopic doughnut, with the crystal-containing pigment in the middle and a tiny metal ring around it. It acts without any external connectors, and the nerve cells are activated without a delay.

“The response time must be short if we are to gain control of the stimulation of nerve cells,” says David Rand, postdoctoral researcher at Tel Aviv University. “Here, the nerve cells are activated directly. We have shown that our device can be used to stimulate not only neurons in the brain but also neurons in non-functioning retinas.”

https://www.sciencedaily.com/releases/2018/05/180502104043.htm

Schizophrenia is associated with structural and functional alterations of the visual system, including specific structural changes in the eye. Tracking such changes may provide new measures of risk for, and progression of the disease, according to a literature review published online in the journal Schizophrenia Research: Cognition, authored by researchers at New York Eye and Ear Infirmary of Mount Sinai and Rutgers University.

Individuals with schizophrenia have trouble with social interactions and in recognizing what is real. Past research has suggested that, in schizophrenia, abnormalities in the way the brain processes visual information contribute to these problems by making it harder to track moving objects, perceive depth, draw contrast between light and dark or different colors, organize visual elements into shapes, and recognize facial expressions. Surprisingly though, there has been very little prior work investigating whether differences in the retina or other eye structures contribute to these disturbances.

“Our analysis of many studies suggests that measuring retinal changes may help doctors in the future to adjust schizophrenia treatment for each patient,” said study co-author Richard B. Rosen, MD, Director of Ophthalmology Research, New York Eye and Ear Infirmary of Mount Sinai, and Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai. “More studies are needed to drive the understanding of the contribution of retinal and other ocular pathology to disturbances seen in these patients, and our results will help guide future research.”

The link between vision problems and schizophrenia is well established, with as many as 62 percent of adult patients with schizophrenia experience visual distortions involving form, motion, or color. One past study found that poorer visual acuity at four years of age predicted a diagnosis of schizophrenia in adulthood, and another that children who later develop schizophrenia have elevated rates of strabismus, or misalignment of the eyes, compared to the general population.

Dr. Rosen and Steven M. Silverstein, PhD, Director of the Division of Schizophrenia Research at Rutgers University Behavioral Health Care, were the lead authors of the analysis, which examined the results of approximately 170 existing studies and grouped the findings into multiple categories, including changes in the retina vs. other parts of the eye, and changes related to dopamine vs. other neurotransmitters, key brain chemicals associated with the disease.

The newly published review found multiple, replicated, indicators of eye abnormalities in schizophrenia. One of these involves widening of small blood vessels in the eyes of schizophrenia patients, and in young people at high risk for the disorder, perhaps caused by chronic low oxygen supply to the brain. This could explain several key vision changes and serve as a marker of disease risk and worsening. Also important in this regard was thinning of the retinal nerve fiber layer in schizophrenia, which is known to be related to the onset of hallucinations and visual acuity problems in patients with Parkinson’s disease. In addition, abnormal electrical responses by retinal cells exposed to light (as measured by electroretinography) suggest cellular-level differences in the eyes of schizophrenia patients, and may represents a third useful measure of disease progression, according to the authors.

In addition, the review highlighted the potentially detrimental effects of dopamine receptor-blocking medications on visual function in schizophrenia (secondary to their retinal effects), and the need for further research on effects of excessive retinal glutamate on visual disturbances in the disorder.

Interestingly, the analysis found that there are no reports of people with schizophrenia who were born blind, suggesting that congenital blindness may completely or partially protect against the development of schizophrenia. Because congenitally blind people tend to have cognitive abilities in certain domains (e.g., attention) that are superior to those of healthy individuals, understanding brain re-organization after blindness may have implications for designing cognitive remediation interventions for people with schizophrenia.

“The retina develops from the same tissue as the brain,” said Dr. Rosen. “Thus retinal changes may parallel or mirror the integrity of brain structure and function. When present in children, these changes may suggest an increased risk for schizophrenia in later life. Additional research is needed to clarify these relationships, with the goals of better predicting emergence of schizophrenia, and of predicting relapse and treatment response and people diagnosed with the condition.”

Dr. Silverstein points out that, to date, vision has been understudied in schizophrenia, and studies of the retina and other ocular structures in the disorder are in their infancy. However, he added, “because it is much faster and less expensive to obtain data on retinal structure and function, compared to brain structure and function, measures of retinal and ocular structure and function may have an important role in both future research studies and the routine clinical care of people with schizophrenia.”

http://www.eurekalert.org/pub_releases/2015-08/tmsh-rcm081715.php