Normally associated with oxidative damage, hydrogen peroxide may prove an unlikely ally in preventing blindness, reports Dick Ahlstrom
Unexpected findings are emerging from research into a number of diseases that cause blindness. They show the release of a substance, normally considered harmful, which helps cells in the eye to survive.
The work relates to apoptosis, the body's highly controlled method for disposing of unwanted or ageing cells, explains Science Foundation Ireland (SFI) principal investigator Prof Tom Cotter.
Based in University College Cork's biochemistry department, Cotter is studying several diseases, including glaucoma, age-related macular degeneration (AMD) and retinitis pigmentosa. All cause premature loss of vision via apoptosis, according to Cotter. "We are trying to understand the signalling pathways that cause that to happen," he says.
He recently received funding worth €1.65 million (including €1.25 million from SFI and €400,000 from Enterprise Ireland) in support of a four-year research effort also being backed by the research charity, Fighting Blindness Ireland. The money will help fund five research fellows, including three who will look at how cells in the retina attempt to survive when under stress and two who will look at a series of chemicals that may help prevent premature retinal cell death.
Surprising results are already emerging, centred on the role of hydrogen peroxide in this process. This chemical is normally associated with oxidative damage, but in the case of retinal cells under stress, the hydrogen peroxide seems to be associated with cell survival, according to Cotter.
Higher levels of the chemical are released when the cell is stressed. "It is as if the dying cell is fighting death," Cotter says. "The preliminary data we have suggests the cell does put up a struggle and fights to survive. We are looking at this stress mechanism in the eye. We have some quite surprising results; for example, that the hydrogen peroxide acts as a survival signal."
When the cells are stressed, the hydrogen peroxide is released and successfully blocks the cell's death.
"After about two hours the hydrogen peroxide levels drop and the cell dies," Cotter explains. "Here we have an oxidant providing a survival signal. Not only do we see it in the eye, but also in leukaemia cells."
The finding has prompted him to look at this process in leukaemia, as blocking the hydrogen peroxide release in cancer cells might afford a way to attack these cells and hasten their death.
The three researchers looking at the process in retinal cells will study where the hydrogen peroxide comes from, where it goes, what it does and what happens to it over time. They will use retinal cell lines and tissues donated by patients.
They have also just acquired the State's first "scanning laser opthalmoscope", says Cotter. The device will enable researchers to look into the retinas of live animals to see what happens to individual cells. "That gives us a real-time view of how the cell is reacting to the stress and how it struggles to survive."
The two other researchers will look at the series of small molecules that seem to inhibit apoptosis, something that may help halt the ongoing loss of retinal cells.
Overall, Prof Cotter heads a team of 15 scientists. The work on eye diseases is important, given that as many as 60,000 adults and children in Ireland are affected by degenerative eye diseases.
AMD is the most common form of registered blindness in this country, affecting one in 10 people over the age of 50. Retinitis pigmentosa is a genetic disease which leads to loss of sight in young adults. Unfortunately, there is no current therapy, according to Cotter.