Review of Ophthalmology

JHU Team Suggests a New View On Photoreceptors and Vision

Staff
6/5/2014

A type of retina cell plays a more critical role in vision than previously known, a team led by Johns Hopkins University researchers has discovered.

Working with mice, the scientists found that the ipRGCs—an atypical type of photoreceptor in the retina—help detect contrast between light and dark, a crucial element in the formation of visual images. The key to the discovery is the fact that the cells express melanopsin, a type of photo-pigment that undergoes a chemical change when it absorbs light.

“We are quite excited that melanopsin signaling contributes to vision even in the presence of functional rods and cones,” postdoctoral fellow Tiffany M. Schmidt said.

Dr. Schmidt is lead author of a recently published study in the journal Neuron. The senior author is Samer Hattar, associate professor of biology in the university’s Krieger School of Arts and Sciences. Their findings have implications for future studies of blindness or impaired vision.

Rods and cones are the most well-known photoreceptors in the retina, activating in different light environments. Rods, of which there are about 120 million in the human eye, are highly sensitive to light and turn on in dim or low-light environments. Meanwhile the 6 million to 7 million cones in the eye are less sensitive to light; they drive vision in brighter light conditions and are essential for color detection.

Rods and cones were thought to be the only light-sensing photoreceptors in the retina until about a decade ago when scientists discovered a third type of retinal photoreceptor—the ipRGC, or intrinsically photosensitive retinal ganglion cell—that contains melanopsin. Those cells were thought to be needed exclusively for detecting light for non-image-dependent functions, for example, to control synchronization of our internal biological clocks to daytime and the constriction of our pupils in response to light.

“Rods and cones were thought to mediate vision and ipRGCs were thought to mediate these simple light-detecting functions that happen outside of conscious perception,” Dr. Schmidt said. “But our experiments revealed that ipRGCs influence a greater diversity of behaviors than was previously known and actually contribute to an important aspect of image-forming vision, namely contrast detection.”

The Johns Hopkins team along with other scientists conducted several experiments with mice and found that when melanopsin was present in the retinal ganglion cells, the mice were better able to see contrast in a Y-shaped maze, known as the visual water task test. In the test, mice are trained to associate a pattern with a hidden platform that allows them to escape the water. Mice that had the melanopsin gene intact had higher contrast sensitivity than mice that lack the gene.

“Melanopsin signaling is essential for full contrast sensitivity in mouse visual functions,” said Dr. Hattar. “The ipRGCs and melanopsin determine the threshold for detecting edges in the visual scene, which means that visual functions that were thought to be solely mediated by rods and cones are now influenced by this system. The next step is to determine if melanopsin plays a similar role in the human retina for image-forming visual functions.”


Additional Vision-Related Cost of Cigarette Smoking
Cigarette smoking and male sex are significant risk factors for developing ocular sarcoidosis, according to a new study presented at the 2014 American Thoracic Society International Conference.

Sarcoidosis is a disease in which inflammation produces granulomas in organs throughout the body, most often in the lungs, but also in the eyes, lymph nodes or skin. Ocular sarcoidosis, which can lead to blindness, affects 25 to 50 percent of sarcoidosis patients.

Droplet Lens Makes Smartphone a Microscope
Australian scientists have invented a simple and cheap way of making a high-powered lens that can transform a smartphone into a high-resolution microscope.

Costing less than a cent, the lenses promise a revolution in science and medicine in developing countries and remote areas.

The lens fabrication technique was invented by Dr. Steve Lee from the Australian National University Research School of Engineering, who collaborated with Dr. Tri Phan from Sydney’s Garvan Institute of Medical Research to find ways to transform the lentil-sized lens into a medical imaging tool.

The lenses are made by using the natural shape of liquid droplets. “We put a droplet of polymer onto a microscope cover slip and then invert it. Then we let gravity do the work, to pull it into the perfect curvature,” Dr Lee said.

“By successively adding small amounts of fluid to the droplet, we discovered that we can reach a magnifying power of up to 160 times with an imaging resolution of four micrometers.” The polymer, polydimethylsiloxane, is the same as that used for contact lenses, and it won’t break or scratch.

“It would be perfect for the Third World. All you need is a fine-tipped tool, a cover slip, some polymer and an oven,” Dr. Lee said.

The first droplet lens was made by accident. “I nearly threw them away. I happened to mention them to my colleague Tri Phan, and he got very excited,” Dr Lee said. “So then I decided to try to find the optimum shape, to see how far I could go.”


Dr. Lee and his team worked with Dr. Phan to design a lightweight 3D-printable frame to hold the lens, along with a couple of miniature LED lights for illumination, and a coin battery.

The technology taps into what the scientists are calling a “citizen science revolution,” which is rapidly transforming owners of smartphones into potential scientists. There are also exciting possibilities for remote medical diagnosis.

Dr. Phan said the tiny microscope has a wide range of potential uses, particularly if coupled with the right smartphone apps. “This is a whole new era of miniaturization and portability—image analysis software could instantly transform most smartphones into sophisticated mobile laboratories,” Dr. Phan said.

“I am most able to see the potential for this device in the practice of medicine, although I am sure specialists in other fields will immediately see its value for them.”

Dr. Lee said the low-cost lens had already attracted interest from a German group interested in using disposable lenses for tele-dermatology.

“There are also possibilities for farmers,” he said. “They can photograph fungus or insects on their crops, and upload the pictures to the Internet where a specialist can identify if they are a problem or not.”

The lensmaking technology is described in the latest issue of Biomedical Optics Express.
 
“Risk factors for ocular sarcoidosis have not been well-studied,” said lead author Adam Janot, MD, of the Virginia Commonwealth University School of Medicine in Richmond. “Accordingly, we reviewed the cases of 109 patients with biopsy-proven sarcoidosis and identified independent risk factors for developing ocular morbidity.”

Of the 109 patients, 21 had ocular sarcoidosis. A significantly higher percentage of patients with ocular sarcoidosis were smokers (71.4 vs. 42 percent, p=0.027) and were male (57.1 vs. 26.1 percent, p=0.009). Median duration of sarcoidosis was 10 years among patients with ocular sarcoidosis and four years among those without (p=0.031).

In analyses adjusting for age, race, sex and other factors, tobacco exposure was associated with a greater than fivefold risk of developing ocular sarcoidosis (odds ratio 5.24, p=0.007, 95% CI 1.58 to 17.41) and male sex was associated with a greater than sevenfold risk (odds ratio 7.48, p=0.002, 95% CI 2.152 to 26.006). Disease duration was no longer significantly associated with developing ocular sarcoidosis in the multivariate analysis. “Our study is the first to correlate smoking and male sex as risk factors for developing ocular manifestations of sarcoidosis,” said Dr. Janot. “If confirmed in other studies, this information may give some insight into the pathology of the disease, can be useful in guiding treatment, and it adds ocular sarcoidosis to the numerous adverse health consequences of tobacco use.”


Trinity Scientists Tie IL-18 to AMD
Scientists at Trinity College
Dublin report a breakthrough with important implications for sufferers of age-related macular degeneration. The group found that a component of the immune system, IL-18, acts as a guardian of eyesight by suppressing the production of damaging blood vessels behind the retina at the back of the eye. In addition, in pre-clinical models, it was shown that IL-18 can be administered in a non-invasive way, which could represent a major improvement on the current therapeutic options that are open to patients.

“We were initially concerned that IL-18 might cause damage to the sensitive cells of the retina, because it is typically linked to inflammation. But surprisingly, we found that low doses had no adverse effects on the retina and yet still suppressed abnormal blood vessel growth,” said Sarah Doyle, assistant professor in immunology at Trinity, who is the first author on the paper.

Dry AMD accounts for the majority of cases, but wet AMD causes more than 90 percent of blindness, generally central, associated with the disease. Because central vision accounts for almost all of our daytime visual acuity, wet AMD sufferers experience severe and profound day-to-day challenges.

The Trinity scientists found that IL-18 directly inhibits vascular endothelial growth factor production, and that it can work as effectively as the current treatment—intravitreal injection—when administered via a non-invasive intravenous injection in pre-clinical settings.

The research was published online in the international journal, Science Translational Medicine.


Orphan-Drug Status for Humira for Uveitis
AbbVie announced that the
Food and Drug Administration granted Humira (adalimumab) orphan drug designation for the treatment of non-infectious intermediate, posterior, or pan-uveitis, or chronic non-infectious anterior uveitis, a group of rare but serious inflammatory diseases of the eye. AbbVie is investigating the efficacy and safety of Humira for the treatment of non-infectious uveitis, and the clinical program is in Phase III development. Humira is not currently approved to treat any form of uveitis.

Uveitis encompasses several inflammatory eye diseases. The associated inflammation causes damage of eye tissue leading to reduced vision and/or vision loss. While the exact cause of uveitis is unknown, this condition can be caused by an infection, autoimmune disease, medication, surgery or trauma to the eye. Symptoms of uveitis may include vision loss, blurred vision, eye pain and redness, as well as sensitivity to light. It is estimated that uveitis accounts for 10 to 15 percent of all cases of total blindness in the United States.

“Few well-characterized treatment options are available for patients suffering from uveitis, and the orphan drug designation recognizes the significant unmet need that exists within this disease,” said Scott Brun, MD, vice president, Pharmaceutical Development, AbbVie. “AbbVie remains committed to the ongoing development of Humira to treat a variety of autoimmune diseases where patients have the potential to benefit.”  REVIEW


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