Beyond 'read-through': Validation of new drugs as therapy for ALL cases of aniridia

Research details

  • Type of funding: Fight for Sight Small Grant Award
  • Grant Holder: Professor Jon Collinson
  • Institute: University of Aberdeen
  • Region: Scotland
  • Start date: January 2020
  • End Date: September 2021
  • Priority: Treatment
  • Eye Category: Inherited retinal
Brief plain language background

Aniridia is an inherited condition that results in the iris (coloured part of the eye) not fully developing. In most cases, this condition is caused by a mutation or fault in a gene called PAX6.

One area of the eye that can be affected is the cornea – the clear surface at the front of the eye. This is known as aniridia-associated keratopathy, resulting in the cornea becoming cloudy and blurring the vision.

What problem/knowledge gap does it help address

The damage to the cornea in aniridia-associated keratopathy occurs when the limbus – an area at the edge of the cornea that maintains its structure – loses function. This is called limbal epithelial stem cell deficiency and leads to severe visual impairment and eventual sight loss.

Current treatments only temporarily reduce the cloudiness of the cornea, as the gene faults responsible for the condition will continue the disease process following treatment.

Aim of the project

To determine the safety and efficacy of two drugs – Duloxetine and Ritanserin – for the treatment of eye defects caused by faults in the PAX6 gene.

Key procedures/objectives

Using a model of the PAX6 gene mutation:

  1. Establish whether the drugs increase the production of PAX6 in corneal cells and limbal epithelial stem cells;
  2. Demonstrate safety when administering the drugs orally and via eye drops;
  3. Investigate whether PAX6 function can be restored in the cornea after treatment;
  4. Determine that symptoms of the condition are improved following treatment.
Potential impact on people with sight loss

If successful, these findings could be used as evidence for a clinical trial where currently, no treatment is available for people living with the blinding condition, aniridia-associated keratopathy.

The project also offers insight into the treatment of other conditions associated with a faulty PAX6 gene, regardless of the specific fault, which could open new treatment avenues.