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Immune cells can treat eye disease in preemies
Retinopathy of Prematurity or ROP, is the main cause of vision loss and blindness in children globally. Damage occurs in the inner region of the retina from supplemental oxygen given to premature infants to overcome distress in their breathing.
Withdrawal of oxygen constricts the blood vessels in the retina. Thereafter, attempts to encourage new blood vessel growth using factors such as vascular endothelial growth factor (VEGF) can over stimulate blood vessel growth. The fragility of the infant eye after these processes can result in hemorrhages that compromise baby's vision.
Current treatment for newborns is laser surgery to burn away damaged blood vessels. A treatment that also damages healthy blood vessels.
Ground-breaking research out of Monash University, Australia, has demonstrated previously unknown disease-fighting immune cells exist within the eye.
Professor Jennifer Wilkinson-Berka in the Central Clinical School, Department of Diabetes, led the team that found regulatory T cells (Tregs), disease fighting white blood cells, exist within the retina.
Wilkinson-Berka: "People thought you couldn't actually have Tregs in eye tissue because the eye, like the brain, has a barrier that stops them from entering. No one had ever described this before, but I thought there might be a weakness in the barrier."
Research on animal models confirmed her suspicions. Researchers then boosted the number of Treg cells confirming Tregs can repair damaged retinal blood vessels and significantly reduce ROP. The work is published in the journal, Nature Communications.
Improving treatments for babies with ROP has become increasingly important as more preemies are being born and are able to live through improved technology. This means more babies are born "smaller and smaller." According to Wilkinson-Berka: "We're seeing what's called a third epidemic of ROP."
Babies less than 1500 grams have a 50 to 70 per cent risk for ROP. Babies under 750 grams have a 98 per cent chance of being affected in some degree.
A small clinical study will now be conducted in collaboration with the Royal Children's Hospital and Murdoch Children's Research Institute that could have far-reaching implications for improving eye disease in people with diabetic retinopathy as well. "The same set of ideas are applicable," explains Professor Wilkinson-Berka. "An estimated 350 million people in the world today have diabetes and large numbers of these will have diabetic retinopathy."
Research into animal models of diabetes will be conducted by the Central Clinical School. Patients with diabetic retinopathy will be treated at the Royal Victorian Eye and Ear Hospital and Centre for Eye Research Australia (CERA) under Associate Professor Lyndell Lim and Dr Sanjeewa Wickremasinghe, beginning in October, 2017.
According to Wilkinson-Berka: "The therapies would not be a cure, but would be added to current treatments to further improve them."
Neovascular retinopathies are major causes of vision loss; yet treatments to prevent the condition are inadequate. The role of regulatory T cells in neovascular retinopathy is unknown. Here we show that in retinopathy regulatory T cells are transiently increased in lymphoid organs and the retina, but decline when neovascularization is established. The decline is prevented following regulatory T cells expansion with an IL-2/anti-IL-2 mAb complex or the adoptive transfer of regulatory T cells. Further, both approaches reduce vasculopathy (vaso-obliteration, neovascularization, vascular leakage) and alter the activation of Tmem119+ retinal microglia. Our in vitro studies complement these findings, showing that retinal microglia co-cultured with regulatory T cells exhibit a reduction in co-stimulatory molecules and pro-inflammatory mediators that is attenuated by CTLA-4 blockade. Collectively, we demonstrate that regulatory T cells are recruited to the retina and, when expanded in number, repair the vasculature. Manipulation of regulatory T cell numbers is a previously unrecognized, and promising avenue for therapies to prevent blinding neovascular retinopathies.
Authors: Devy Deliyanti, Dean M. Talia, Tong Zhu, Mhairi J. Maxwell, Alex Agrotis, Jack R. Jerome, Emily M. Hargreaves, Steven Gerondakis, Margaret L. Hibbs, Fabienne Mackay and Jennifer L. Wilkinson-Berka
The research into diabetic retinopathy, previously supported by the Central Clinical School, has been bolstered by a grant of US $750,000 from the Juvenile Diabetes Research Foundation (JDRF). In addition, Dr Devy Deliyanti, first author of the paper, has recently been awarded a three-year JDRF Fellowship.
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Retinopathy of Prematurity or ROP, can lead to blindness in preemies. But, Treg cells can repair damaged retinal blood vessels and significantly reduce ROP. Image credit: Brian Hall, WikiMedia.