Rescuing human light-sensors in a common form of Leber congenital amaurosis

14 April 16

written by:

Ade Deane-Pratt

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Fight for Sight-funded scientists successfully test new potential treatment for severe inherited childhood sight loss

Scientists at UCL Institute of Ophthalmology have found out what causes damage to the eye in a common type of severe sight loss that affects young children. The results also point to a potential new treatment that may one day be possible to deliver by eye injection.

Leber congenital amaurosis (LCA) is the name for a group of disorders in which ‘photoreceptor’ cells in the light-sensitive layer of the eye (the retina) degenerate and die, causing sight loss or blindness. It’s passed on through families and symptoms start in early childhood with night-blindness and being sensitive to light.

Around 1 in 5 people with LCA have a specific genetic fault that affects a protein called CEP290. Previous research has shown that CEP290 is important for making the part of a photoreceptor that sticks out from the cell body like an antenna and responds to light.

Blind cells

Without this antenna (called ‘the outer segment’) photoreceptors are blind to light. This means they can’t do their usual job of turning light into an electrical signal that the brain can make sense of.

Tests on skin cells from people with this type of LCA have found they contain less than half the amount of healthy CEP290 protein compared to people without LCA. And in this study the research team tested cells from the retina.

Results from the study showed that photoreceptors in particular make significantly less CEP290 than other cells. This explains why their outer segments are so badly affected.

‘Antisense’ treatment overrides fault

And the most promising result was that treatment with a type of molecule called an ‘antisense morpholino’ could override the genetic fault and get the photoreceptors showing signs that they were working again.

Cartoon image of photoreceptors with damaged (left) and normal (right) outer segments at the top.  Detail from the 'graphical abstract' for Parfitt et al 2016.
Cartoon of photoreceptor cells before (left) and after (right) 'antisense' treatment.

“This is really encouraging because it’s the functional interaction between photoreceptor proteins that will be critical to whether the treatment can restore vision,” said Dr Amelia Lane, a research associate at UCL Institute of Ophthalmology and a first author on the study. “CEP290 is not suitable for most current approaches to gene therapy but a recent study in normal mice showed that eye injection with the same class of molecule could become a practical therapeutic option.”

Dr Dolores M Conroy is Director of Research at Fight for Sight. She said:

“Developing a treatment that could restore vision or slow slight loss is the top priority for research on inherited eye disorders as identified by patients, relatives, carers and health professionals in the Sight Loss and Vision Priority Setting Partnership and so these results are highly relevant as well as promising. However, we now need to translate these findings, using antisense therapy, into patients. In addition, this approach could be used to treat other inherited retinal disorders.”

Dr Lane’s work on the study was funded by Fight for Sight. The results are published in the journal Cell Stem Cell.

Read the full press release (PDF) (text) and find out more about the research project, below.

Developing light-sensitive cells for transplant therapy and as a test-bed for potential new treatments

1 October 14 - 1 September 17

Turning stem cells into photoreceptors.

Find out more