Tuesday, 11 October 2016

Improving the treatment of eye diseases using regenerative medicine

ISTM recently ran a blog writing competition that was open to PhD students and young researchers with a view to improving their lay-writing skills and helping ISTM to play a greater role in the public dissemination of its research. After concluding the competition we will be publishing each entry in turn over the coming months. The 3rd prize winner of our competition was Rachel Gater, a PhD student in the Centre for Doctoral Training, ISTM.


(Source: Microsoft word - Clip Art)
The retina is a complex layer of tissue at the back of the eye. It turns the visual information entering the eye into electrical signals, which are then sent to the brain for processing. Eye diseases such as glaucoma and macular degeneration can damage the retina, leading to significant sight problems and even blindness if left untreated. Glaucoma causes damage to the retina by a build up of pressure inside the eye, whilst macular degeneration involves deterioration of the centre of the retina; the most sensitive region. Although there are some existing treatments for eye diseases such as intravitreal injections and surgery, the success rate of these treatments is not very high and they can cause unpleasant side effects. Therefore, scientists in the field of regenerative medicine are working to develop better treatments for eye diseases.

There are generally two methods that scientists in the field of regenerative medicine can try when researching new treatments for eye diseases. The first approach is the possibility of triggering self repair processes (endogenous regeneration) to help the damaged eye tissues repair themselves. Certain amphibians, such as the newt, are already naturally able to replace their entire eye through endogenous regeneration! We still don’t fully know how amphibians do this, but it is believed that they store stem cells in certain areas of the eye. Stem cells are special because they have not yet transformed into a specific cell type and can therefore be triggered to turn into any type of cell. Therefore if the amphibian’s eye gets injured, the stored stem cells can replace any damaged cells and repair the eye. If scientists can work out the biology of exactly how amphibians do this, then they may be able to help trigger the same process for humans in the future!

(Source: Microsoft word - Clip Art)
Figure 1: Amphibians such as the newt are already naturally able to replace their entire eye through self repair processes (endogenous regeneration).

The second approach scientists in the field of regenerative medicine can try is the possibility of repairing damaged eye tissues using stem cell therapies. Stem cell therapies can be generated from sources such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs). As shown in Figure 2, the retina of the eye is made up of many layers each containing different types of cells. These cells include rods (which help us with vision in darkness at night time) and cones (which help us with colour vision in the day time). There are also bipolar cells which do a bit more processing in the nuclear + plexiform layers, as well as ganglion cells which are important in helping to pass on information to the brain. As we know that stem cells can be triggered to turn into any type of cell, scientists believe that we might be able to turn stem cells into new retina cells such as rods, cones and ganglion cells. If successful, these cells could then be used to repair the retina if the eye gets damaged by disease or injury.

(Source: original)
Figure 2: The retina is made up of many layers each containing different types of cell.

So far scientists have been able to turn stem cells into rods, cones and ganglion cells inside a cell culture plate, but there is more work to do before the method can become a treatment given to patients. Even though we can grow the cells, one of the first challenges is figuring out how we can safely deliver the treatment into the patient’s eye. As the eye is so small and fragile, injection needles or surgery may cause further damage to the eye. Therefore, it is important to figure out the best way to precisely deliver the cells to the eye without it causing further damage or being painful for the patient. A second challenge is getting the cells to integrate and function correctly once they are inside the eye. Even if we can deliver the cells correctly, we would need to make sure that the cells are alive, in the correct place and performing their correct function once inside. For example, if we manage to deliver new cone cells into the eye and they correctly perform their role in colour vision, then we would know that the treatment has worked! Finally, a third challenge scientists will need to overcome is the possibility of immune-rejection. As stem cell therapies don’t always use the patient’s own cells, there is a chance that transplanted cells may be rejected, in the same way that a heart transplant might be rejected after heart transplantation surgery. To overcome this challenge, drug treatments such as immuno-suppression therapy may be used to help reduce the risk of rejection. Alternatively scientists might be able to use a patient’s own stem cells which would not be rejected by the body.

In summary, due to the low success rate of current treatments, scientists in the field of regenerative medicine are working to develop better treatments for eye diseases. The two main methods for this include the possibility of triggering self repair (endogenous regeneration) like amphibians can do naturally, or the use stem cell therapies to repair damaged eye tissues. Although scientists can turn stem cells into retina cells relatively successfully in a cell culture plate, challenges still need to be overcome. These challenges include figuring out how to safely deliver cell therapies into the eye, getting transplanted cells to function correctly once inside the eye and overcoming the risk of immune-rejection. If scientists can successfully overcome these challenges, these approaches are likely to transform the way that we treat eye diseases in the future!

Written by Rachel Gater, PhD Student, Centre for Doctoral Training, ISTM
(3rd Prize in the ISTM Blog Post Competition 2016)