Powerful anti-inflammatory molecule may block vision loss in diabetic retinopathyJanuary 03, 2017
AUGUSTA, Ga. (Jan. 3, 2017) - A more powerful version of an anti-inflammatory molecule already circulating in our blood may help protect our vision in the face of diabetes.
Diabetic retinopathy resulting from high circulating levels of glucose is the leading cause of blindness in adults. Now scientists have evidence that a man-made version of soluble gp130, or sgp130, that is 10 times more powerful than the natural one, may help avoid high levels of inflammation in the eye that occur in diabetes and avert the retinal destruction that typically follows.
"What we are trying to do is inhibit this pathway so there will be no more signaling," said Dr. Shruti Sharma, vascular and endothelial biologist in the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Augusta University.
Sharma is talking about the pro-inflammatory cascade that can result when high levels of glucose in the blood prompt high circulating levels of the immune-system driver IL-6. High circulating IL-6 has been found in the blood as well as the fluid portion of the eyes of patients with diabetic retinopathy. When circulating levels of IL-6 increase, so do levels of its receptor, IL-6R, which is required for IL-6 to be active.
These floating inflammation drivers enable something called trans-signaling - where receptors aren't directly found on the affected cells themselves - and there is emerging evidence from Sharma's lab and others that it's a major player in inflammation-driven diseases like diabetic retinopathy, inflammatory bowel disease, even atherosclerosis.
In this case, the body appears to have a check system: Sgp130 also is traveling in the bloodstream where it can essentially trap the IL-6/IL-6 receptor complex and keep it from crossing cell membranes to promote inflammation. However, in the altered face of diabetes, apparently its action is not always sufficient.
That's why Sharma's new $1.5 million grant from the National Eye Institute is enabling the first attempt to target IL-6 trans-signaling in diabetic retinopathy with this synthetic, more powerful version of sgp130, called sgp130-Fc, which is already in clinical trials for Crohn's disease and rheumatoid arthritis.
The MCG research team hopes its work in human serum and mouse models will lead to clinical trials of sgp130-Fc in diabetic retinopathy as well.
In fact, Sharma's lab has early evidence in both human tissue and diabetic mice retinas that inhibiting this IL-6 trans-signaling significantly reduces the classic eye inflammation and the destruction that follows.
IL-6 receptors aren't always circulating, rather sometimes can be found directly on cell membranes. On white blood cells, for example, Il-6 naturally binds to its receptor on the cell membrane; that binding recruits gp130, which is also attached to the membrane, to help send a signal for action. In fact, even when IL-6 and its receptor successfully bind in the bloodstream, they gain access and action in the eye by hooking up with gp130 in the membrane of the endothelial cells that line the eye's microscopic vasculature.
Endothelial cells, which are early targets in diabetic retinopathy, don't have IL-6 receptors, which is where trans-signaling comes in, said Dr. Ashok Sharma, bioinformatics and genomics expert in the Center for Biotechnology and Genomic Medicine and a study co-investigator. He notes that it's not yet clear whether endothelial cells, which line blood vessels throughout the body, have IL-6 receptors in other environs.
The new grant is enabling the MCG scientists to further explore in a mouse model of type 1 diabetes the effects of trans-signaling on the endothelial cells as well as pericytes in the eye. Pericytes are contractile cells that wrap around endothelial cells, enhancing the strength of the smallest blood vessels, like where the arterial system and venous system come together so oxygen- and nutrient-rich blood can nourish the eye then depleted blood can exit.
In diabetic retinopathy, pericytes are damaged and destroyed; blood vessels walls unnaturally thicken; and blood passageways narrow. Eventually, endothelial cells also die. The eyes will attempt to grow new blood vessels as a fix, but the new vessels are ultimately dysfunctional and leaky and instead further destroy vision.
The scientists also are looking to see if the powerful sgp130-Fc can help. In their mouse model of diabetic retinopathy, they are giving their drug both before the disease develops to better understand its impact, as well as later in the disease process, which is when patients might one day receive treatment. They are injecting it directly into the eye, as anti-vascular endothelial growth factor treatments today are given, as well as intravenously to look at the difference in impact.
Sophisticated technology, such as optical coherence tomography, is enabling the scientists to keep a real-time, non-invasive eye on the health of the retina as they work.
While there is evidence that trans-signaling always promotes inflammation, classic signaling with the receptor on the cell surface can turn inflammation up or down. Current diabetic retinopathy therapies include laser and anti-VEGF therapies that target dysfunctional blood vessels.
Co-investigators also include Dr. Sylvia Smith, retinal cell biologist and chair of the MCG Department of Cellular Biology and Anatomy, and Dr. Ruth Caldwell, cell biologist in the MCG Vascular Biology Center.
Medical College of Georgia at Augusta University
Related Diabetes Articles:
There has been no known link between diabetes and vitamin A -- until now.
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
Although insulin-producing cells are found in the endocrine tissue of the pancreas, a new mouse study suggests that abnormalities in the exocrine tissue could cause cell non-autonomous effects that promotes diabetes-like symptoms.
A new study published in The Lancet Diabetes & Endocrinology journal suggests that reducing sugar content in sugar sweetened drinks (including fruit juices) in the UK by 40 percent over five years, without replacing them with any artificial sweeteners, could prevent 500,000 cases of overweight and 1 million cases of obesity, in turn preventing around 300,000 cases of type 2 diabetes, over two decades.
Women with gestational diabetes who consistently and continuously breastfeed from the time of giving birth are half as likely to develop type 2 diabetes within two years after delivery, according to a study from Kaiser Permanente published today in Annals of Internal Medicine.
Related Diabetes Reading:
Bright Spots & Landmines: The Diabetes Guide I Wish Someone Had Handed Me
by Adam Brown (Author), Kelly L. Close (Foreword)
Adam Brown’s acclaimed diaTribe column, Adam’s Corner, has brought life-transforming diabetes tips to over 1 million people since 2013. In this highly actionable guide, he shares the food, mindset, exercise, and sleep strategies that have had the biggest positive impact on his diabetes – and hopefully yours too! Bright Spots & Landmines is filled with hundreds of effective diabetes tips, questions, and shortcuts, including what to eat to minimize blood sugar swings; helpful strategies to feel less stressed, guilty, and burned out; and simple ways to improve exercise and... View Details
The End of Diabetes: The Eat to Live Plan to Prevent and Reverse Diabetes
by Dr. Joel Fuhrman (Author)
The New York Times bestselling author of Eat to Live and Super Immunity and one of the country’s leading experts on preventive medicine offers a scientifically proven, practical program to prevent and reverse diabetes—without drugs.
At last, a breakthrough program to combat the rising diabetes epidemic and help millions of diabetics, as well as those suffering with high blood pressure and heart disease. Joel Fuhrman, M.D. Research director of the Nutritional Research Foundation, shows you how to live a long, healthy, and happy life—disease free. He... View Details
The Diabetes Code: Prevent and Reverse Type 2 Diabetes Naturally
by Jason Fung (Author), Nina Teicholz (Foreword)
From acclaimed author Dr. Jason Fung, a revolutionary guide to reversing diabetes.... View Details
Dr. Neal Barnard's Program for Reversing Diabetes: The Scientifically Proven System for Reversing Diabetes Without Drugs
by Neal Barnard (Author)
Tackle diabetes and its complications for good with this newly updated edition of Dr. Neal Barnard's groundbreaking program.
Revised and updated, this latest edition of Dr. Barnard’s groundbreaking book features a new preface, updates to diagnostic and monitoring standards, recent research studies, and fresh success stories of people who have eliminated their diabetes by following this life-changing plan.
Before Dr. Barnard’s scientific breakthrough, most health professionals believed that once you developed diabetes, you were stuck with it—and could... View Details
Choose Your Foods: Food Lists for Diabetes
by American Diabetes Association (Author)
The standard for diabetes meal planning for over 60 years, this edition features updated carbohydrate, protein, and fat information for a wide variety of foods and beverages and replaces exchange terminology with choices. Includes tips on exercise, reading food labels, and a glossary of diabetes related terms. View Details
Diabetes For Dummies
by Alan L. Rubin (Author)
The straight facts on treating diabetes successfully
With diabetes now considered pandemic throughout the world, there have been enormous advances in the field. Now significantly revised and updated, this new edition of Diabetes For Dummies includes the latest information on diabetes medications and monitoring equipment, new findings about treating diabetes in the young and elderly, new ways to diagnose and treat long- and short-term complications, updated nutritional guidelines, new tools for measuring blood sugar and delivering insulin to the body, and much more.
There's... View Details
The Official Pocket Guide to Diabetic Food Choices
by American Diabetes Association ADA (Author)
Completely updated to match the newest edition of Choose Your Foods: Food Lists for Diabetes Meal Planning, this pocket-sized guide is now better and more complete than ever.
Every day and at every meal, millions of people use the food list system to plan meals, make healthier choices, and better estimate portions. This proven system is the most popular approach to diabetes meal planning and has been used by dietitians, diabetes educators, and millions of people with diabetes for more than 70 years. This portable version of the Food Lists takes all of the information from... View Details
Diabetic Living Diabetes Meals by the Plate: 90 Low-Carb Meals to Mix & Match
by Diabetic Living Editors (Author)
An easy, graphic guide to planning delicious, diabetes-friendly meals This innovative, graphic cookbook offers the easiest and most flavorful way to build complete meals that are diabetes-friendly and delicious. Sidestepping complex programs that turn meal-planning into work, the 90 complete meals in Diabetes Meals by the Plate follow the Plate Method—a simple approach to eating the right foods in proper amounts by filling your plate with one half nonstarchy vegetables, one quarter protein, and one quarter starch. A clever photo style showing every meal in its three... View Details
What Do I Eat Now?: A Step-by-Step Guide to Eating Right with Type 2 Diabetes
by Patti B. Geil R.D. (Author), Tami A. Ross R.D. (Author)
Any person diagnosed with diabetes has one simple question: What do I eat now? When diagnosed with type 2 diabetes, doctors typically tell their patients to start eating healthy. But what does that mean? If figuring out what to eat seems like taking a test, here’s the solution, the American Diabetes Association book, What Do I Eat Now?. Written in clear, concise, and down-to-earth language that takes the mystery out of confusing nutrition recommendations, this indispensable guide can help readers make lasting changes in as little as a month. In only 4 weeks, readers can eat... View Details
Mayo Clinic The Essential Diabetes Book
by Mayo Clinic (Author)
More people than ever before have diabetes. The disease affects an estimated 21 million adults and children in the US and many people with the disease don't have it under control. Unlike years ago, you have a good chance of living an active and healthy life with diabetes - provided you work with your health-care team to take the necessary steps to control your blood sugar. This title covers: the pre-diabetes stage — taking charge to prevent diabetes; types of diabetes; symptoms and risk factors; treatments and strategies for managing your blood sugar; avoiding serious complications;... View Details