Characterising the retina and subsequent damage in a model of Mucopolysaccharidosis Type IIIC

Research details

  • Type of funding: RCOphth / Fight for Sight Zakarian Award
  • Grant Holder: Dr Christos Iosifidis
  • Institute: Manchester Royal Eye Hospital
  • Region: North West
  • Start date: December 2023
  • End Date: November 2024
  • Priority: Understanding
  • Eye Category: Inherited retinal
Brief Lay background

Mucopolysaccharide (MPS) diseases are a group of rare, life limiting metabolic disorders resulting in a problem with lysosomal function. Lysosomes are the “recycling centres” of cells, involved in a continual cycle of replacing used materials and breaking them down to be removed from cells. The faults in the genes causing MPS diseases mean an enzyme involved in this process is either absent or malfunctioning, resulting in a build-up of waste products in cells that cause progressive damage.

What problem/knowledge gap does it help address

Mucopolysaccharidosis type IIIC, abbreviated to MPSIIIC, is one version of MPS. Typically diagnosed in childhood, MSPSIIIC is caused by faults in a gene called HGSNAT. MPSIIIC can affect the body in several ways, including the brain and eyes.

Recently, it has been shown that individuals with milder faults in the HGSNAT gene are present in individuals who only have vision problems – called non-syndromic retinitis pigmentosa – which leads to progressive vision loss. This condition is characterised by progressive damage to the retina – the specialised light-sensitive tissue at the back of the eye.

There is no clear understanding of how the eye is affected in patients with faults in the HGSNAT gene – and there is no current treatment for this condition.

Aim of the project

To investigate how the retina is affected in a model of MPSIIIC and how these affects contribute to retinal damage.

This award will also help the researcher gain key skills for a career in vision research, including eye-related laboratory skills, improved understanding of genetic eye disease and genetic therapies, and research management and design.

Key procedures/objectives

The research team will perform a series of tests using a mouse model of MPSIIIC:

  1. Electroretinography (ERG) – measures the electrical activity of retinal cells in response to light to determine retinal function.
  2. Optical coherence tomography (OCT) – pictures of the retina to identify structural changes.
  3. Histology – using a microscope to look at retinal cells to establish chemical changes.
  4. Biochemical analysis – measuring the quantity of HGSNAT enzyme and waste product in the retina to understand how the condition affects retinal health.
Potential impact on people with sight loss

Carrying out these experiments is necessary to understand how this newly recognised condition affects the retina. The research project will act as a first step towards a knowledge base that is essential when exploring treatment options.