Nav: Home

New findings show promise for treatment of Graves' disease and other ocular disorders

November 11, 2016

Philadelphia, PA, November 11, 2016 - A new class of therapies may be on the horizon for thyroid eye disease (TED) and other destructive scarring conditions. At least 50% of patients with Graves' disease, an autoimmune disease that primarily attacks the thyroid gland, develop eye problems including inflammation, discomfort, scarring, and bulging eyes. Abnormal over-production and activation of collagen-producing myofibroblasts underlie many of these conditions. A new study published in The American Journal of Pathology found that activation of the aryl hydrocarbon receptor (AHR) pathway by its ligands blocks collagen production and myofibroblast proliferation in TED.

"Currently there are no effective therapies for TED that target or prevent the excessive scarring and tissue remodeling. Our studies reveal that AHR is a novel target for treatment of this disease and potentially other diseases that manifest with excessive scarring," explained lead investigator Richard P. Phipps, PhD, of the Department of Environmental Medicine and Flaum Eye Institute of the School of Medicine and Dentistry of the University of Rochester (Rochester, New York).

The primary goals of the research were to better understand the molecular pathways underlying scarring in TED and to control or prevent tissue remodeling or destruction. The orbital remodeling in TED is likely induced by infiltrating T lymphocytes and mast cells, which activate orbital fibroblast effector cells to either proliferate and form scar-producing cells called myofibroblasts or turn into pro-inflammatory fat cells. Myofibroblasts produce large amounts of extracellular matrix material such as collagen, are contractile, and secrete a variety of cytokines and chemokines, all of which enhance scar formation.

The investigators focused on studying the activity of AHR, a transcription factor that is known to play a key role in regulating inflammatory and immune responses, and the effects of two AHR ligands (ITE and FICZ). Previous research had shown that AHR activation decreases transforming growth factor beta (TGFβ), a cytokine that induces myofibroblast formation. When human orbital fibroblasts from TED patient tissue were compared to tissue from patients without TED, the researchers discovered that TED orbital fibroblasts expressed higher levels of AHRs than non-TED orbital fibroblasts.

The AHR ligands turned on AHR-dependent genes and blocked the TGFβ-driven transformation of human orbital fibroblasts to scar-forming myofibroblasts. The ligands also interfered with other aspects of TED tissue remodeling including collagen production, filament formation, and myofibroblast contraction. Importantly, the ligands impaired myofibroblast function without affecting cell viability.

"We also showed for the first time that AHR signaling in primary human orbital fibroblasts disrupts the pro-fibrotic Wnt/β-catenin pathway, which is important for scar cell formation," noted Dr. Phipps. Wnt/β-catenin has been shown to play a crucial role in other fibrotic diseases such as pulmonary fibrosis and hypertrophic scar formation.

"We are excited that our translational research team of clinicians and basic researchers have come together to present these novel findings and hope that future studies and trials based on this work can move forward to bring targeted therapies for TED," commented Dr. Phipps.

Each year, approximately one million Americans are diagnosed with Graves' eye disease. Symptoms may range from irritation and dryness to characteristic protrusion of the eyes, eyelid retraction, vision impairment, light sensitivity, and blindness in the most severe cases. Symptoms can be managed by artificial tears for dryness, prednisone for double vision, radiation therapy to reduce swelling and double vision, or surgical decompression. Smoking is known to exacerbate TED.
-end-


Elsevier Health Sciences

Related Collagen Articles:

Collagen fibers encourage cell streaming through balancing act
Engineers from the McKelvey School of Engineering at Washington University have shown that the length of collagen fibers has a roll to play in the ability of normal cells to become invasive.
Preserving old bones with modern technology
A team of University of Colorado Boulder anthropologists is out to change the way that scientists study old bones damage-free.
Study shows BioCell collagen can visibly reduce common signs of skin aging within 12 weeks
In one of the most substantial studies of a skin health supplement, BioCell Collagen®, was found to visibly reduce common signs of skin aging, including lines and wrinkles, within 12 weeks of daily use.
3D printing new parts for our broken hearts
Researchers have developed a 'FRESH' new method of 3D printing complex anatomical structures out of collagen -- a primary building block in many human tissues.
I see the pattern under your skin
By combining multiphoton imaging and biaxial tissue extension a research team from Japan found that collagen in the skin is organized in a mesh-like structure, and that elastic fibers -- the connective tissue found in skin -- follows the same orientation.
GW pilot study finds collagen to be effective in wound closure
Researchers in the George Washington University Department of Dermatology found that collagen powder is just as effective in managing skin biopsy wounds as primary closure with non-absorbable sutures.
Confining cell-killing treatments to tumors
Researchers at the Koch Institute for Integrative Cancer Research at MIT have developed a technique to prevent cytokines escaping once they have been injected into the tumor, by adding a Velcro-like protein that attaches itself to the tissue.
Collagen fibres grow like a sunflower
In a new study published in EPJ E, two researchers at the Universite Paris-sud in Orsay, France, examine the patterns developed by collagen fibers, found in the tissues of virtually all animals.
Evidence for human involvement in extinction of megafauna in the late Pleistocene
By re-dating giant ground sloth remains found in the Argentinian Pampas region using more advanced technology, scientists say they have provided evidence that humans hunted and butchered this animal near a swamp during the end of the Pleistocene.
Collagen nanofibrils in mammalian tissues get stronger with exercise
A recent experimental study conducted by researchers at the University of Illinois at Urbana-Champaign, Washington University in St.
More Collagen News and Collagen Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.