An enzyme under study to treat certain cancers is also showing promise in reducing the significant vision damage that can result from diabetes and premature birth, scientists report.
Inflammation is considered a hallmark of cancer. Its pervasive as well in both of these potentially blinding eye conditions, in which inadequate oxygen to the eyes prompts growth of new blood vessels to better deliver oxygen, but which instead often obstruct the vision pathway and become leaky, which causes swelling, further hindering vision.
Scientists at the Medical College of Georgia report in newly published studies in the journals Cell Death and Disease and Cells, increasing evidence that making more of the enzyme arginase 1, or A1, available helps alleviate these unhealthy responses and interrupt a natural body response that promotes destructive ongoing, high levels of inflammation in both diabetic retinopathy and retinopathy of prematurity.
Key to the process is making less of the amino acid L-arginine available. With diabetes, for example, high blood sugar and lipid levels as well as oxidative stress increase expression of inducible nitric oxide synthase, or iNOS, which uses the L-arginine to help produce even more inflammation and promote disease progression. The way its supposed to work is iNOS goes up in response to an infection then high-expressing A1 cells move in to turn iNOS off and inflammation down.
Thats because A1 competes with iNOS for L-arginine. They theorized that more A1, which actually breaks down L-arginine into two products, would make less L-arginine available to feed this (unhealthy) iNOS explosion, and help tamp down the vicious cycle of inflammation and related damage, says William Caldwell, PhD, pharmacologist and chair emeritus of the MCG Department of Pharmacology and Toxicology.
If you reduce L-arginine levels, iNOS cannot work. This will make things better, Caldwell says.
As a great example about how everything in the body is about balance, the powerful blood vessel dilator NO, or nitric oxide, which iNOS makes, is good for blood vessels and blood pressure when it is produced at low levels by the endothelial cells that line blood vessels. This NO has the added benefit of being anti-inflammatory. But the toxic high levels produced by iNOS result in production of more reactive oxygen species, which feeds inflammation, which basically rusts whatever tissue it touches, Caldwell says.
They found that when a diabetic, obese mouse that eats constantly and develops a condition similar to early stage diabetic retinopathy is given A1 three times a week for two weeks, it improves their visual acuity and enables the rodents to better distinguish degrees of darkness, like shades of grey.
The mice had less oxidative stress and inflammation in the retina, restoration of the protective blood retinal barrier to help avoid leakage of tiny capillaries and the swelling and damage that would follow, and reduced progression of diabetic retinopathy, says Ruth B. Caldwell, PhD, cell biologist in the MCG Vascular Biology Center.
Conversely, they have shown that mice which express only half the usual amount of A1 have more abnormal blood vessel growth and retinal injury, they write. William Caldwell notes that when A1 is completely eliminated, mice and people will die of ammonia poisoning because another important ongoing job of A1 is constantly working in the liver to help eliminate ammonia, which is produced when proteins, a basic building block of the body, are broken down.
Thats how A1 occupies so much L-arginine, which it cleaves or cuts to form urea, a form of ammonia which can be eliminated in the urine, and l-ornithine, which is important to normal physiological functions like cell proliferation and collagen formation.
The MCG scientists also have shown that A1 is naturally present in the immune cells and retinal cells of mice with oxygen-induced retinopathy, a common model for the destructive blood vessel growth that occurs in retinopathy of prematurity. The model also is used to mimic some aspects of diabetic retinopathy because diabetic mice dont live long enough to develop full-blown eye disease. Theyve also found A1 present in the retinas of humans with diabetic retinopathy and in blood samples of young patients with retinopathy of prematurity.
AIs anti-inflammatory power is exhibited in the way it can keep those immune cells, called macrophages, which can both promote and reduce inflammation, from becoming too proinflammatory, Ruth Caldwell says.
She notes that numerous antioxidants and other anti-inflammatory agents have been tried and failed to help patients with these conditions. What we think is happening is this pegylated A1 is reducing within these immune cells the ability to make inducible nitric oxide synthase in big amounts. We think that is the deal.
A1 normally breaks down in a matter of minutes, so like with studies in cancer, which also cannot grow and survive without L-arginine, they used a manmade pegylated, or stable, form that instead stays around for days.
New, accessible therapies are needed to help avoid the vision consequence of both type 1 and 2 diabetes as well as retinopathy of prematurity, the Caldwells say. Their studies indicate that in diseases where the blood retinal barrier is broken, A1 can penetrate the eye making shots directly into the eye unnecessary, which should make treatment much more accessible, the scientists say. Anti-VEGF (vascular endothelial growth factor) therapy, for example, used to also combat the growth of abnormal and leaky blood vessels, requires injections into the back of the eye.
The Caldwells are co-corresponding authors on the two new papers. Abdelrahman Y. Fouda, PhD, Ruth Caldwells former postdoctoral fellow who is now on the faculty of the University of Arkansas for Medical Sciences College of Medicine, is first author on the Cell Death and Disease paper. Ammar A. Abdelrahman, PhD, a postdoc in William Caldwells lab, is first author on the Cells paper.
The scientific team has already shown that administering pegylated A1 improves protection in ischemia/reperfusion injury, when oxygen supply is lost for a limited time, like with a knife injury, then the blood supply gets restored; in major optic nerve trauma; and following an ischemic stroke, by far the most common stroke type where a clot typically cuts off the blood and oxygen supply to a part of the brain.
The research projects were supported by the National Eye Institute, the James and Jean Culver Vision Discovery Institute at Augusta University and the Department of Veterans Affairs.
Read the studies here and here.
Like Love Haha Wow Sad Angry
See original here:
Powerful enzyme that tamps down inflammation holds promise for protecting eyes in diabetes, premature birth - Jagwire Augusta
- Vascular Cell and Molecular Biology | Center for Vascular Biology | Weill Cornell ... - April 13th, 2018 [April 13th, 2018]
- APVBO-Asia Pacific Vascular Biology Organization Conference - April 18th, 2018 [April 18th, 2018]
- Vascular Biology Conferences | Vascular Surgery ... - May 5th, 2018 [May 5th, 2018]
- Vascular Discovery: From Genes to Medicine - May 7th, 2018 [May 7th, 2018]
- 2019 Vascular Cell Biology Conference GRC - May 26th, 2018 [May 26th, 2018]
- Biology 211: Taxonomy of Flowering Plants - June 7th, 2018 [June 7th, 2018]
- esm-evbo2019.org - Menu - July 27th, 2018 [July 27th, 2018]
- Vascular Biology | Pulmonary, Allergy, Sleep & Critical ... - November 16th, 2018 [November 16th, 2018]
- Lower vascular plant | biology | Britannica.com - November 18th, 2018 [November 18th, 2018]
- Vascular Biology - NAVBO - November 20th, 2018 [November 20th, 2018]
- 2019 Cerebral Vascular Biology Conference - cvent.com - November 21st, 2018 [November 21st, 2018]
- PPARs and Their Emerging Role in Vascular Biology ... - November 26th, 2018 [November 26th, 2018]
- Vascular Biology Chicago Medicine - November 30th, 2018 [November 30th, 2018]
- Vascular Biology | Society for Vascular Surgery - November 30th, 2018 [November 30th, 2018]
- Vascular Biology 2018 - NAVBO - December 19th, 2018 [December 19th, 2018]
- Vascular Biology 2019 - NAVBO - December 20th, 2018 [December 20th, 2018]
- Vascular Biology - January 22nd, 2019 [January 22nd, 2019]
- pvb2019.org Plant Vascular Biology Conference 2019 - January 31st, 2019 [January 31st, 2019]
- Plant Physiology | Basic Biology - March 12th, 2019 [March 12th, 2019]
- Awards - esm-evbo2019.org - April 23rd, 2019 [April 23rd, 2019]
- Medication and Exercise to Prevent Muscle Loss - Next Avenue - September 24th, 2019 [September 24th, 2019]
- A Snail as Fast as a Bullet, and Other Darwin-Defying Marvels - Discovery Institute - September 24th, 2019 [September 24th, 2019]
- Nature up close: Life in the Humboldt Penguin National Reserve - CBS News - September 24th, 2019 [September 24th, 2019]
- Oklahoma new hires and promotions announced - Oklahoman.com - September 24th, 2019 [September 24th, 2019]
- Quinn Capers IV, MD - TCTMD - September 24th, 2019 [September 24th, 2019]
- Cardiovascular Repair And Reconstruction Devices Market Global Industry Insights by Top Vendors, Growth, Revenue and Forecast Outlook 2019-2025 -... - September 26th, 2019 [September 26th, 2019]
- Four health projects at Boston Childrens Hospital that could help adults - The Boston Globe - September 30th, 2019 [September 30th, 2019]
- Research Officer/ Postdoctoral Researcher - The Conversation AU - October 16th, 2019 [October 16th, 2019]
- UNSW skin cancer researcher Levon Khachigian hit with string of retractions - ABC News - October 16th, 2019 [October 16th, 2019]
- Michal Wszola: We Expect to Transplant the Bioprinted Bionic Pancreas in Three to Five Years - 3DPrint.com - October 24th, 2019 [October 24th, 2019]
- 'The Blob': This mysterious 'smart' slime can solve puzzles and make decisions - CNBC - October 24th, 2019 [October 24th, 2019]
- University of Maryland and DOD collaborate to study Tick-borne Infections using 3-D models of human blood vessels - Outbreak News Today - November 19th, 2019 [November 19th, 2019]
- Submerged Vegetation Mirrors Coast's Health - Coastal Review Online - November 19th, 2019 [November 19th, 2019]
- Another health warning for e-cigarette users that has nothing to do with lung disease - MarketWatch - November 19th, 2019 [November 19th, 2019]
- E-Cigarettes Take a Dangerous Toll on Heart Health - DocWire News - November 19th, 2019 [November 19th, 2019]
- Vascular biology Department of Surgery College of ... - November 19th, 2019 [November 19th, 2019]
- US Nobel laureates tell us what they think about cancer research, moonshots, the dark side, funding, meritocracy, herd mentality, Trump, and joy - The... - November 21st, 2019 [November 21st, 2019]
- Growing Organs in the Lab: One Step Closer to Reality - BioSpace - November 21st, 2019 [November 21st, 2019]
- Inotrem Announces Enrollment of First Patient in its Phase IIb ASTONISH Trial for Nangibotide in the Treatment of Septic Shock - Business Wire - November 21st, 2019 [November 21st, 2019]
- Another Study Suggests E-cigarettes Hurt Heart Health More Than Regular Cigarettes - Science Times - November 21st, 2019 [November 21st, 2019]
- Cleveland Clinic awarded $12 million by NIH to study the link between gut microbes and heart disease - Crain's Cleveland Business - November 21st, 2019 [November 21st, 2019]
- JanOne Acquires Worldwide, Exclusive License for Promising Treatment of Peripheral Arterial Disease (PAD) - Yahoo Finance - November 27th, 2019 [November 27th, 2019]
- Germ-free lungs of newborn mice are partially protected against hyperoxia - The Mix - November 27th, 2019 [November 27th, 2019]
- Bethesda Health Physician Group Welcomes Fellowship-Trained Endocrine Surgeon Jessica L. Buicko, MD, to Its Team - The Boca Raton Tribune - November 27th, 2019 [November 27th, 2019]
- 9 Harvard researchers named AAAS Fellows Harvard - Harvard Gazette - November 27th, 2019 [November 27th, 2019]
- Top Technical Advances of 2019 - The Scientist - December 29th, 2019 [December 29th, 2019]
- Growing up Tyrannosaurus rex: Osteohistology refutes the pygmy Nanotyrannus and supports ontogenetic niche partitioning in juvenile Tyrannosaurus -... - January 2nd, 2020 [January 2nd, 2020]
- UCC currently taking applicants for 21 jobs with some incredible pay - Cork Beo - January 2nd, 2020 [January 2nd, 2020]
- Vascular Biology | Surgery Research | Michigan Medicine ... - January 2nd, 2020 [January 2nd, 2020]
- Sandy Bottom wetlands to receive protection for 'national ecological significance' - Citizen Times - January 14th, 2020 [January 14th, 2020]
- Why biotech is a boon for patients and investors - Spear's WMS - January 14th, 2020 [January 14th, 2020]
- Exonate Announces Collaboration With Janssen to Develop a New Eye Drop for the Treatment of Retinal Vascular Diseases Including Wet Age-related... - January 14th, 2020 [January 14th, 2020]
- G-protein Coupled Receptor Market Competitive Research And Precise Outlook 2019 To 2025 Dagoretti News - Dagoretti News - January 18th, 2020 [January 18th, 2020]
- Scientists revealed the oldest known scorpion on Earth - Tech Explorist - January 18th, 2020 [January 18th, 2020]
- How biology creates networks that are cheap, robust, and efficient - Penn: Office of University Communications - January 18th, 2020 [January 18th, 2020]
- Genome editing heralds new era of disease research, therapy - The Augusta Chronicle - January 18th, 2020 [January 18th, 2020]
- Research Fellow in Vascular Stem Cell Biology job with QUEENS UNIVERSITY BELFAST | 195527 - Times Higher Education (THE) - February 10th, 2020 [February 10th, 2020]
- More than skin deep: the latest innovation in 3D printing - Med-Tech Innovation - February 10th, 2020 [February 10th, 2020]
- Examining the link between menopause and heart disease risk - Medical News Bulletin - February 10th, 2020 [February 10th, 2020]
- Women Face an Increased Risk of Heart Disease With AgeRunning Can Help - runnersworld.com - February 12th, 2020 [February 12th, 2020]
- G-protein Coupled Receptor Market Competitive Research And Precise Outlook 2019 To 2025 - Galus Australis - February 15th, 2020 [February 15th, 2020]
- Valentine's Day Matters of the Heart, Biopharma-Style - BioSpace - February 15th, 2020 [February 15th, 2020]
- The Addicted Gardener: Environmental tidbits from around the world - Wicked Local Sharon - February 22nd, 2020 [February 22nd, 2020]
- UI at 150 & Beyond: 'The Quad was the best no matter what the weather' - Champaign/Urbana News-Gazette - February 22nd, 2020 [February 22nd, 2020]
- The Addicted Gardener: Environmental tidbits from around the world - Wicked Local Dedham - February 23rd, 2020 [February 23rd, 2020]
- THE ADDICTED GARDENER: Environmental tidbits from around the world - Wicked Local Wareham - March 22nd, 2020 [March 22nd, 2020]
- 'Little Foot' skull reveals how this more than 3 million year old human ancestor lived - HeritageDaily - March 22nd, 2020 [March 22nd, 2020]
- It's Not Only About Neurons - The Good Men Project - March 22nd, 2020 [March 22nd, 2020]
- Who is Sir Patrick Vallance and what is his role in government during coronavirus outbreak? - The Scottish Sun - March 22nd, 2020 [March 22nd, 2020]
- University of Washington Pathology Professor Dies of COVID-19 - The Scientist - March 22nd, 2020 [March 22nd, 2020]
- THE ADDICTED GARDENER: Environmental tidbits from around the world - Wicked Local Rochester - March 23rd, 2020 [March 23rd, 2020]
- Ancient human ancestor 'Little Foot' probably lived in trees, new research finds - WBAP News/Talk - March 23rd, 2020 [March 23rd, 2020]
- Study shows similarity in anti-VEGF injection intervals for wet AMD - Ophthalmology Times - March 25th, 2020 [March 25th, 2020]
- aTyr Pharma and its Hong Kong Subsidiary, Pangu BioPharma, Announce Government Grant to Fund Bispecific Antibody Development Platform - BioSpace - March 25th, 2020 [March 25th, 2020]
- Health researchers find solution to life-threatening side effect - Mirage News - March 25th, 2020 [March 25th, 2020]
- European Vascular Biology Organisation | Advancing human ... - March 25th, 2020 [March 25th, 2020]
- Vascular Biology Program | Boston Children's Hospital - March 25th, 2020 [March 25th, 2020]
- Vascular Biology Research Program | Johns Hopkins ... - March 25th, 2020 [March 25th, 2020]
- Anatomy of a heatwave: how Antarctica recorded a 20.75C day last month - The Conversation AU - April 1st, 2020 [April 1st, 2020]
- Who is Sir Patrick Vallance and is he speaking at todays government coronavirus press briefing? - The Sun - April 1st, 2020 [April 1st, 2020]