Creating new ways to study eye conditions

Using cells donated by people affected by eye conditions and turning them into stem cells, Prof Majlinda Lako has recreated the retina in the lab. This technique could be used to develop and test new drugs, leading to more effective targeted treatments.

To learn more about diseases and develop new treatments, scientists recreate simplified versions of the disease known as ‘models’. During her career, Professor Majlinda Lako has worked with and modelled diseases using embryonic stem cells. Sourced from very early embryos, these stem cells are theoretically able to develop into any cell type in the body.

But breakthrough discoveries in 2006 and 2007, in Japan and USA, found that it was possible to create stem cells in the lab from mature cells, such as blood or skin cells. The cells generated were called ‘induced Pluripotent Stem Cells’ (iPSCs). The technique opened the possibility of using cells donated by patients to model their disease. 

Studying Retinitis Pigmentosa

Fight For Sight awarded Majlinda funding in 2013 to create iPSCs to study Retinitis Pigmentosa – an inherited retinal disease where peripheral vision and night vision are lost over time.

Via a collaborator in Leeds, people with Retinitis Pigmentosa donated skin cells for Majlinda to convert into iPSCs. Creating iPSCs from patient cells meant that the model could more closely recreate the disease as it really develops.

From these iPSCs the team generated ‘retinal organoids’ – clumps of cells that look and behave like a foetal retina. These organoids contain photoreceptors as well as retinal pigment epithelial cells, the layer of cells which supports and nourishes the rest of the retina.

Mutations in the PRPF31 gene are a common cause of Retinitis Pigmentosa. Majlinda and her team discovered that these mutations lead to faulty proteins accumulating in the retinal pigment epithelial cells. This causes the cells to die, which in turn affects the photoreceptors, leading to progressive sight loss.

Majlinda is now using the Retinitis Pigmentosa iPSCs to test gene therapy approaches which restore the production of functional PRPF31 protein. Her hope is that gene therapy at an early age could prevent damage to the retinal pigment epithelial cells, and so prevent further sight loss.

Kinder retinoblastoma treatments

Majlinda has also turned to modelling retinoblastoma, taking a similar approach to the Retinitis Pigmentosa model. With funding from Fight For Sight, Majlinda and her team generated iPSCs from blood cells donated by children with retinoblastoma. They found the retinal organoids generated from these iPSCs replicate many of the features of the tumours found in children.

Majlinda and her team at Newcastle University are now using the retinoblastoma iPSC organoids to test drugs repurposed from other diseases. The most promising drugs could eventually be tested in early clinical trials, which could one day bring more targeted, kinder treatments for children.

Created by patients, for patients

Majlinda has deposited the iPSCs into the European Bank for induced pluripotent Stem Cells (EBiSC), which allows other researchers access to these cells for their own research.

The iPSC models would not exist without patients agreeing to donate their cells. She therefore feels a duty to make sure that research using the iPSCs really makes a difference for people: “For us, [they’ve] always been a resource created by the patients, for the patients.”