Developing molecular and genetic therapies for Late-onset Retinal Degeneration

Brief plain language background 

Late-onset retinal degeneration (L-ORD) is a rare inherited eye disease that causes progressive vision loss later in life. It is passed down in families and usually leads to severe sight loss. While people with L-ORD can receive support, such as genetic counselling and visual aids, there are currently no treatments available. This condition has a major impact on those affected and their families. A key barrier to developing treatments is that scientists still do not fully understand what causes the disease at the cellular level. 

Previous research has shown that changes (mutations) in a gene called C1QTNF5 cause L-ORD. This gene produces a protein found in the retinal pigment epithelium (RPE), cells that are vital for healthy vision. We want to better understand how these gene changes harm the RPE and explore potential ways to fix or reduce this damage. 

What problem/knowledge gap does it help address 

Currently, there are no treatments for L-ORD. Those living with the condition face inevitable sight loss. There is limited understanding of how specific mutations in C1QTNF5 cause damage in the eye and the exact changes they cause in the RPE to affect the healthy function of these cells is not clear. 

Without detailed knowledge of the cellular problems these mutations cause, it is difficult to design or test treatments. We do not know whether different mutations lead to the same type of cell damage, or if treatment must be tailored to each type. This project will address these gaps by creating “disease-in-a-dish” models of L-ORD using cells from patients. These models will help us pinpoint the exact problems in the RPE and test whether early experimental treatments can help restore normal function. 

Aim of the project 

To study how different genetic mutations in the C1QTNF5 gene affect RPE cells in L-ORD, and identify whether these cellular changes can be reversed using therapies that target faulty genetic information or instructions to make C1QTNF5 protein. This will help guide development of future treatments for this currently untreatable condition. 

Potential impact on people with sight loss 

This research is an essential early step in developing treatments for L-ORD. By better understanding how specific mutations damage the retinal pigment epithelium, we can design targeted therapies to prevent or slow vision loss. The use of patient-derived cells allows us to test treatments in a lab setting that closely mimics the real disease. If successful, this work could lead to clinical trials within 5–10 years, offering new hope to families affected by this currently untreatable condition. Ultimately, it could pave the way for personalised treatments based on a person’s specific genetic mutation.