“It takes a village. But I think it’s a big village.”

Professor Majlinda ‘Linda’ Lako and researcher and lecturer Marzena Kurzawa-Akanbi are working together at Newcastle University to understand how retinal cells are affected by age-related macular degeneration (AMD).

In this Q&A, they talk about their research, what they’ve discovered so far, what motivates them and why continued funding is so important.

Please would you introduce yourselves?

Linda: I’m team leader of the stem cell research group at Newcastle University, and I’ve been researching macular disease since 2013. Marzena has been with me on this journey since 2017, looking at how retinal cells function with AMD.

Marzena: I'm a co-investigator on this latest project. It’s a continuation of the journey in the understanding of AMD using different systems, looking at the different mechanisms. That's how it has evolved.

Can you tell us more about this research, and how it began?

Linda: Back at the beginning, we started in the lab with two patients who had progressive wet AMD, and two unrelated people who didn’t have the genetic change and didn’t have AMD. We derived the patients’ stem cells, characterised them and then started making the retinal cells.

It was very exciting because it was really the first time that we could apply the theoretical knowledge in the lab to such a major blinding disease as AMD.

In every project we’ve pushed ourselves a little bit further. The preliminary data in 2017 showed that the waste disposal ‘machinery’ was blocked. That was a very serendipitous finding. The waste disposal is how cells process their waste and try to get it out of the cells and recycle it to make new proteins.

In Newcastle, we have a very strong team that deals with waste disposal, and we were just chatting with them. That's how scientists work, over a coffee! The team leader said, ‘why don't you just give us some cells and we'll have a look?’

The next day he phoned me and said, ‘these cells are full of waste, they can't process it.’ And that's how the second project came about, because we thought if the waste cannot be disposed of, but we can help the cells somehow to dispose of it, maybe we can make them a bit healthier.

Marzena: In 2016 I was working on a project focusing on Parkinson's disease and dementia – neurodegenerative disorders associated with brain cell loss.

This is when my interest in extracellular vesicles (tiny cell-originated packages which deliver messages, proteins and genetic material to other cells) started. There weren't many people working on that at the time, trying to understand what vesicles do in a cellular system and whether they are actually a real biological entity doing something apart from removing waste from cells.

That's how we started to work together, Linda and I. We thought that, as Linda said, the cells are overwhelmed with waste - maybe extracellular vesicle release could be one of the mechanisms that could get rid of that burden of waste.

And that’s how we started the project: we looked into the production of the vesicles by cells from healthy individuals and cells from patients with AMD.

How is eye healthcare improving, and what could this mean for people with macular disease?

Marzena: We have better tools being developed. For example, optical coherence tomography (OCT) is very, very important in macular disease diagnosis. If you're at risk, and even if not, you should have your eye checks regularly, and OCT is at present the best tool in picking up the earliest changes. For example, in optical coherence tomography, you could see accumulation of drusen, which is the waste material. That's a signpost that the condition might be developing.

As long as we identify and pick up the signposts of a condition early enough, we could implement specific changes, even as small as lifestyle changes, which could make a huge difference.

I think a lot could be done with early diagnostics, the early understanding that the signposts of the conditions are there. So if you’re at risk of developing macular disease, you could do something now before it develops into a full-blown condition.

Linda: We know AMD is a complex condition. Multiple factors contribute to it, but it's thanks to the understanding that we have developed, and are still developing, that we can now say you potentially have the power to influence your risk.

Marzena: I think it's really beautiful science, using complex approaches and state-of-the-art methodologies to understand the condition and what's happening, and then applying it to patient biology and trying to prevent it in the first place.

What motivates you to do this research?

Linda: I was always more motivated by the patient stories. And also, my mum has early AMD and glaucoma which does give it a personal slant. I had some drusen-like deposits identified in my eyes a while ago, but there hasn't been any progression.

Marzena: I guess what attracts me to the research is that it’s a story that we’re building. It’s the handbook that we’re writing. It is to deepen our understanding of what's happening in the condition.

I want to expand the breadth of research to be able to treat a condition, or diagnose a condition, from the earliest moment possible. If we can develop our research findings into something translational that could be used in the clinic later down the line, that would be absolutely wonderful.

Why is continued funding for macular disease research so important?

Linda: I don't think since 2013 we've had a day where the Macular Society didn't fund us. We've developed a very nice relationship!

It has helped us maintain the skills and develop a strong group. I think for us this is another drive. Whenever we have lab meetings, I remind my team: this is patient money, we need to make good use of it, we cannot waste it, we have to be very careful with it.’

And especially what we do - stem cell research is very expensive. It takes time and resilience. Because you go home and you think ‘my cells are dying, what can I do?’ You keep thinking about it because it's not an experiment you can repeat within a week.

Marzena: It's important to mention that this is more than a job, it’s a vocation. It’s a lifestyle. It's not about coming to work and ticking off the tasks that you’ve done. You don't go home and stop thinking about it. If you have a problem, you dream about it, and usually the solutions actually come in your dreams. Honestly, I talk from experience.

The will to help patients is really driving the research that we do. I think this is why we all do it, why we turn up to work every day.