Dry Eye Disease (DED) is the most common ocular surface disorder, affecting approximately 350 million people worldwide and causing persistent eye irritation, blurred vision, pain and decreased quality of life. DED is characterised by a loss of homeostasis of the eye’s tear film and a vicious cycle of corneal epithelial damage and inflammation.

The newly-published study evaluated Link_TSG6 in two validated mouse models of DED: an autoimmune model where NOD.B10.H2 mice spontaneously develop dry eye disease, and the desiccating stress model that mimics DED caused by environmental factors. Results from the study showed that topically administered Link_TSG6 (e.g., twice a day for 7 days) dose-dependently reduced corneal epithelial defects and suppressed inflammatory markers while increasing tear production and conjunctival goblet cell density. At the highest Link_TSG6 dose, no corneal lesions remained in approximately 50% of treated eyes. In addition, Link_TSG6 was significantly more effective than Restasis^â, the market leading treatment, at reducing corneal epithelial erosions and reducing inflammation.
 

“There is a desperate need for treatments that rapidly and significantly improve the signs and symptoms of Dry Eye Disease,” said Dr Joo Youn Oh from Seoul National University College of Medicine, a corresponding author of the paper. “The present findings support the viability of Link_TSG6 as a promising drug candidate that both suppresses inflammation and promotes repair of the cornea – critical steps in overcoming the pathophysiology of Dry Eye Disease."

The study showed that Link_TSG6 suppresses the levels of inflammatory cytokines on the ocular surface and inhibits the infiltration of Th1 and Th17 immune cells into the lacrimal glands and lymph nodes, indicative of the protein's multiple anti-inflammatory effects.

Professor Tony Day, a co-corresponding author, from the Wellcome Centre for Cell-Matrix Research, University of Manchester, said: "Link_TSG6 is a biological drug that harnesses the protective effects of TSG-6, a protein that is made in our bodies in response to inflammation and injury.  It is extremely rewarding to obtain such compelling preclinical data with our novel treatment approach for Dry Eye Disease. We hope to further progress this work by advancing Link_TSG6 towards human clinical trials. It is our ambition to see Link_TSG6 approved and available to patients with DED."

Caroline Milner, a Founder of Link Biologics, said: “The publishing of this research is a major accomplishment in our journey towards finding an effective treatment for Dry Eye Disease, which could improve the lives of millions around the world.  The team is working diligently to build on these findings and secure additional funding to reach our next milestone."

The full paper "The Link module of human TSG-6 (Link_TSG6) promotes wound healing, suppresses inflammation and improves glandular function in mouse models of Dry Eye Disease" is available

An international team of scientists has identified a protein which is strongly linked to the commonest cause of blindness in developed countries when its levels are raised in the blood.

The discovery is a major step forward in the understanding of age-related macular degeneration, which affects 1.5 million people in the UK alone.

The study, carried out by the team from Universities of Manchester, Cardiff, London and Nijmegen, and 91ֱ�� Foundation NHS Trust is published in Nature Communications.

The major funder was the Medical Research Council and the study

The protein, called FHR4, was found by the team to be present at higher levels in the blood of patients with AMD compared to individuals of a similar age without the disease.

The findings were confirmed in 484 patient and 522 control samples from two independent collections across Europe.

Analyses of eyes donated for research after life also revealed the FHR4 protein was present in the AMD-affected parts of the eye

FHR4 was shown by the team to activate part of the immune system -called the complement system; over activation is a major causal factor of AMD.

FHR4 is one of a group of proteins that regulate the complement system and the genes encoding these proteins are tightly clustered on chromosome 1, the largest human chromosome.

When the team investigated a set of genetic variants across the human genome, they found that genetic variants in this region on chromosome 1 determined the levels of FHR4 in the blood. And they found that the same genetic variants were associated with AMD.

Professor Paul Bishop and Professor Simon Clark, from the University of Manchester were part of the leadership team on the study.

Professor Bishop, who is also a Consultant Ophthalmologist at 91ֱ�� Royal Eye Hospital, said: “The combined protein and genetic findings provide compelling evidence that FHR4 is a critical controller of that part of the immune system which affects the eyes.

“We have shown that genetically determined higher blood FHR4 levels leads to more FHR4 in the eye which in turn increases the risk of the uncontrolled immune system response that drives the disease.

“So apart from improving understanding of how AMD is caused, this work provides a way of predicting risk of the disease by simply measuring blood levels of FHR4.

He added: “It also provides a new route to treatment by reducing the blood levels of FHR4 to restore immune system function in the eyes.

“Because treatments options for AMD are limited, this comprehensive understanding of the biology of AMD is a huge boost for scientists finding answers to a problem which causes untold misery for thousands of people in the UK alone.”

Professor Simon Clark, a specialist in the regulation of the complement system in health and disease said: “This study really is a step-change in our understanding of how complement activation drives this major blinding disease.

“Up until now, the role played by FHR proteins in disease has only ever been inferred. But now we show a direct link and, more excitingly, become a tangible step closer to identifying a group of potential therapeutic targets to treat this debilitating disease.”

"Increased circulating levels of Factor H Related Protein 4 are strongly associated with age-related macular degeneration" is published in Nature Communications

Photo: Keith Williamson

Scientists from The University of Manchester have found a way to trick the eye into thinking the world is brighter than it actually is.

Using a chemical compound, the team activated a small group of retinal neurons in dim light, which unexpectedly made almost the whole retina more active.

Though more research is needed, the study provides new insight into how the retina communicates with the brain when animals respond to different situations.

The retina is a thin layer of tissue that lines the back of the eye which receives light focused by the lens, and convert it into neural signals which are sent to the brain.

The manipulation, carried out in mice, effectively increased the “bandwidth” of communication from the retina to the brain.

The research was funded by Medical Research Council, European Research Council and the National Centre for Replacement, Refinement and Reduction of Animal Research (NC3Rs). It is published in published in PNAS.

The discovery led by Professor Rob Lucas from The University of Manchester, uncovers an important principle underlying the way in which different areas of the nervous system communicate with each other.

Retinal neurons convey visual information to the brain a sequence of electrical pulses

Using the analogy of a digital communication channel, neural communication uses up a lot of energy so its bandwidth must be optimised according to changes in demand.

Since the 1990s, scientists have shown that on average brain activity is limited to between 1 to 5 electrical pulses per second per neuron.

However at any given time, some parts of the brain may demand many more pulses to perform optimally.

Dr Riccardo Storchi, who was on the team said: “This discovery provides some important insight into a simple mechanism by which flexible allocation of energy resources is regulated by the retina.

“This effect is mediated by specialist neurons known as ‘intrinsically photosensitive retinal ganglion cells’ (ipRGCs) which act like a light-meter, regulating communication between retina and the brain.

“We have known for a while that neuron pulses are energetically expensive, but until now we didn’t understand what regulates their frequency. This is a first step which we hope will tackle this important question.”

The paper Photoreceptive retinal ganglion cells control the information rate of the optic nerve is available 

Hearing aids and cataract surgery are strongly linked to a slower rate of age-related cognitive decline, according to new research by University of Manchester academics.

According to and , cognitive decline- which affects memory and thinking skills- is slowed after patient’s hearing and sight are improved.

The rate of decline was halved following cataract surgery and was 75% less following the adoption of hearing aids.

The research on cataract surgery - which is published in  today– was carried out using 2,068 individuals who underwent cataract surgery between Wave 2 and Wave 6 of the English Longitudinal 91ֱ�� of Ageing survey from between 2002 to 2014.

They were compared with 3,636 individuals with no cataract surgery.

And the research on hearing aids, published in the Journal of the American Geriatrics Society in July, was carried out using 2040 participants in the American Health and Retirement survey from 1996 to 2014

Both surveys assess cognitive decline by testing memory, asking participants to recall 10 words immediately and then at the end of the cognitive function module.

The researchers compared the rates of decline before and after the patients had surgery or started wearing a hearing aid.

Dr Dawes said: “These studies underline just how important it is to overcome the barriers which deny people from accessing hearing and visual aids.

“It’s not really certain why hearing and visual problems have an impact on cognitive decline, but I’d guess that isolation, stigma and the resultant lack of physical activity that are linked to hearing and vision problems might have something to do with it.

“And there are barriers to overcome: people might not want to wear hearing aids because of stigma attached to wearing them, or they feel the amplification is not good enough or they’re not comfortable.

“Perhaps a way forward is adult screening to better identify hearing and vision problems and in the case of hearing loss, demedicalising the whole process so treatment is done outside the clinical setting. That could reduce stigma.

“Wearable hearing devices are coming on stream nowadays which might also be helpful. They not only assist your hearing, but give you access to the internet and other services

Dr Maharani said: “Age is one of the most important factors implicated in cognitive decline. We find that hearing and vision interventions may slow it down and perhaps prevent some cases of dementia, which is exciting- though we can’t say yet that this is a causal relationship.

“Other studies have attempted to look at rates of cognitive decline- but have not really succeeded as it’s hard to take into account demographic factors.

“But the beauty of this study is that we’re comparing the progress of the same individuals over time.”

‘’ is published in Plos One.

‘’ is published in the Journal of the American Geriatrics Society

This research is funded by the European Commission’s Horizon 2020 Framework