Breaking News
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Excessive daytime sleepiness in OSA patients linked to greater risk for cardiovascular diseases
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - Celiac disease may be caused by stomach bug in childhood
February 15, 2019 - NHS performance figures highlight the true scale of Emergency Department crisis
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
Study could provide novel treatment strategy for potentially blinding problem

Study could provide novel treatment strategy for potentially blinding problem

image_pdfDownload PDFimage_print

An enzyme known to help our liver get rid of ammonia also appears to be good at protecting our retina, scientists report.

Our retina, which captures light and converts it into neural signals that go to the brain so we can see, can be damaged or destroyed by conditions that reduce blood flow like diabetes, glaucoma or hypertension.

“We are trying to figure out what we can do to ameliorate that damage, to lessen the initial injury, and promote better recovery,” says Dr. Ruth B. Caldwell, cell biologist, in the Vascular Biology Center at the Medical College of Georgia at Augusta University.

Caldwell and her colleagues have the first evidence that the enzyme arginase 1 may do both by suppressing inflammation produced by big white blood cells called macrophages.

Their findings indicate that arginase 1 therapy, which is already in clinical trials for cancer, could provide a novel strategy for this potentially blinding problem, they report in the journal Cell Death & Disease.

Macrophages are known to move in to an area damaged by disease or injury and clean up debris, even consume invaders like bacteria, but they also have a role in regulating inflammation.

M1 macrophages are generally thought to promote inflammation and M2s are more associated with collagen production, wound healing and repair. When inflammation isn’t present, the majority of your macrophages are likely M2s, which make arginase 1, says Caldwell, the study’s corresponding author.

“Basically when we remove arginase 1, the macrophages are more inflammatory, more damaging, and when we add it back, they are less inflammatory, more reparative,” says Dr. Abdelrahman Y. Fouda, postdoctoral fellow in Caldwell’s lab and the study’s first author.

The study was the first to look at the role of arginase 1 in ischemic retinopathy using a common model called ischemia reperfusion injury, in which blood flow is removed then restored, which, like ischemic retinopathy, also induces destructive inflammation, oxidative stress and resulting damage to neurons and blood vessels.

There are currently no effective therapies for the neurovascular injury of ischemic retinopathy.

For their studies, the scientists looked at normal mice as well as those with arginase 1 knocked out bodywide, specifically from macrophages or from the endothelial cells that line blood vessels.

The import of arginase 1 on retinal health in the face of an ischemic injury was clear both when it was removed and when it was added.

Deleting the enzyme from the endothelial cells had no effect, but without it, macrophages produced a bigger inflammatory response to lipopolysaccharide, a component of the membrane of gram-negative bacteria.

Removing arginase 1 from macrophages generally worsened retinal injury, retinas became thinner and distorted and more neurons were lost, suggesting a major, protective role for macrophages containing arginase 1, the scientists say.

When they administered a more stable but still human grade of the enzyme, called pegylated arginase 1, it reduced inflammation and subsequent retinal damage following reperfusion injury in normal mice.

Pegylated arginase 1 already has been shown to be safe and of some benefit in early trials of advanced and highly lethal liver cancer. In the case of cancer, it appears to reduce the availability of the amino acid L-arginine, which arginase regularly scarfs up and which some cancers must have, so they die, says Dr. William Caldwell, pharmacologist, retired chair of the MCG Department of Pharmacology and Toxicology and study coauthor.

In the eye, while they don’t yet know if adding arginase 1 really converts M1s to M2s, they definitely see less destructive inflammatory response in the retina.

“Let’s just say they behave differently,” Ruth Caldwell says of these immune cells that show up presumably to help. There also are likely other benefits when arginase 1 shows up since it also produces things like polyamines, compounds that are known to be good for neurons, she says.

Like macrophages, arginase has two forms, which also appear to have polar opposite effects. In the face of ischemic retinopathy, when macrophages become pro-inflammatory, they increase their level of arginase 2 and decrease levels of arginase 1.

The MCG scientists have found that deleting arginase 2 decreases cell death by inflammation, while deleting arginase 1 increases it, prompting upregulation of damaging factors like tumor necrosis factor alpha and inducible nitric oxide synthase, or iNOS.

While nitric oxide is generally considered a good thing, iNOS occurs in inflammation, producing very high levels that can contribute to oxidative stress and illustrating the need for balance, William Caldwell says.

The Caldwells are co-principal investigators on a new $1.5 million National Eye Institute grant that is enabling them to look further at the impact of both arginases when the disease has become chronic and treatment is needed for extended periods as a patient likely would.

They want to know whether in this scenario administration of pegylated arginase 1 also has undesirable effects like raising blood pressure.

As with most things, the impact of arginase 1 is about location, says William Caldwell. Inside the lining of the blood vessels, for example, it’s considered bad because it competes with nitric oxide synthase for the L-arginine it needs to make nitric oxide and keep blood vessels open.

“If in a chronic model we find bad side effects, we may need a targeted therapy to deliver arginase 1 directly to the macrophages,” Fouda says. For their studies to date, the enzyme has been injected into the eye and given systemically and short term, no more than a few hours after the injury.

They also are looking further at the role of arginase 1 in neurovascular injury, whether a major way it protects, as they suspect, is by promoting reparative macrophages, and generally exploring its therapeutic potential.

They also want to know more about the impact of arginase 2, which their previous studies have shown to be a bad guy in ischemic retinopathy, but which is largely unexplored in macrophages in this scenario.

“We think they may have opposite functions and that is part of understanding the whole picture,” Ruth Caldwell says. So they are now looking at what arginase 2 does in the oxygen-compromising disease states retinopathy of prematurity, which occurs in premature babies, as well as high-fat diet models like type 2 diabetes.

They have already shown that following retinal injury, arginase 2 and iNOS levels go up while arginase 1 decreases.

Turkey, peanuts and pumpkin seeds are great sources for L-arginine, which teams up with arginase to help the liver eliminate ammonia, a byproduct of the body’s constant use of proteins that can be lethal if it’s not regularly eliminated.

Ruth Caldwell notes that there are relatively few macrophages of any type in our eyes until damage attracts them. In their ischemia reperfusion model, they think macrophages move in from the blood.

Source:

http://www.augusta.edu/mcg/

About author

Related Articles