Molecular mechanism of opsin transport and its relevance to photoreceptor degeneration
Research details
- Type of funding: PhD Studentship
- Grant Holder: Dr Andy Grierson
- Institute: The University of Sheffield
- Region: North East
- Start date: October 2019
- End Date: August 2024
- Priority: Causes
- Eye Category: Inherited retinal
The human visual system detects light through proteins known as opsins. These are found in specialized cells of the eye, called photoreceptor cells. Opsins are not evenly distributed across the entire cell but instead are highly concentrated in a morphologically distinct compartment known as the photoreceptor outer segment.
Since the outer segment is gradually replaced over time, opsins are continuously transported into it, which is essential for photoreceptor function and survival. It is known that defects in opsin transport are extremely damaging to the photoreceptor cell and result in its rapid death, leading to blindness.
When transport is defective, opsin starts to accumulate in the wrong part of the cell where it is toxic. In fact, many forms of human inherited blindness result from opsin transport defects. In order to cure these forms of blindness, the mechanisms that mediate opsin transport must be understood.
Researchers aim to identify proteins that bind opsin and move it into the photoreceptor outer segment.
A novel genetic approach, in an animal model, will be used to identify proteins that mediate opsin transport. Additionally, a biochemical purification technique, known as tandem affinity purification, can identify proteins that bind opsin and facilitate its transport. In order to achieve this, a fragment of opsin that is known to mediate its transport will be fused with a tag. This tag retains opsin and its binding partners while other proteins are washed away.
This research will identify new causes of retinal degeneration as opsin interacting proteins are likely to be key for the toxic environment. The toxicity of opsin may be diminished by blocking the function of opsin-binding proteins with small chemical compounds which can be easily applied to the eye.
Since the outer segment is gradually replaced over time, opsins are continuously transported into it, which is essential for photoreceptor function and survival. It is known that defects in opsin transport are extremely damaging to the photoreceptor cell and result in its rapid death, leading to blindness.
When transport is defective, opsin starts to accumulate in the wrong part of the cell where it is toxic. In fact, many forms of human inherited blindness result from opsin transport defects. In order to cure these forms of blindness, the mechanisms that mediate opsin transport must be understood.
Researchers aim to identify proteins that bind opsin and move it into the photoreceptor outer segment.
A novel genetic approach, in an animal model, will be used to identify proteins that mediate opsin transport. Additionally, a biochemical purification technique, known as tandem affinity purification, can identify proteins that bind opsin and facilitate its transport. In order to achieve this, a fragment of opsin that is known to mediate its transport will be fused with a tag. This tag retains opsin and its binding partners while other proteins are washed away.
This research will identify new causes of retinal degeneration as opsin interacting proteins are likely to be key for the toxic environment. The toxicity of opsin may be diminished by blocking the function of opsin-binding proteins with small chemical compounds which can be easily applied to the eye.