BMS2048 Neuroscience – Practical 2
The Structure of the Mouse Retina
Introduction
Retinitis Pigmentosa (RP) is a genetic disorder that results in the degradation of photoreceptors in the retina. This leads to difficulties with night vision, reduced peripheral vision and eventually the complete loss of visual activity. It’s inherited as an autosomal dominant, autosomal recessive, as well as an X-linked trait. A small percentage of people with this disorder have a mutation in the gene that codes for the β-subunit of the enzyme phosphodiesterase (PDE). To further understand the nature of this disease, we studied rd1 mice. These animals also have a mutation in the gene that codes for the β-subunit of PDE, leading to the degeneration of photoreceptors …show more content…
The rd1 mouse shows severe degeneration of photoreceptors with the pigmented epithelial cells collapsing in on the inner nuclear layer.
Discussion By comparing the wild type with the rd1 mouse, it’s clear that not all cell types are destroyed. Only the photoreceptors are degraded, whilst the other cell types are preserved. We can therefore conclude that the retinal degeneration mutation only effects the expression of the photoreceptors. Without the β-subunit of PDE, the photoreceptors are unable to break down cGMP, and therefore unable to close their sodium ion channels, allowing the receptors to continue firing even in the presence of light. This means that they cannot respond to any light stimulus, and are degraded as a consequence. Using these results we could potentially find a way to cure blindness in humans with similar retinal degeneration mutations. Since we’ve deduced that the loss of visual activity is solely due to the lack of the β-subunit of PDE in rd1 mice, we need to find a way of correcting/replacing the mutation so the cells can produce functional PDEs. This could potentially be achieved through continuous gene therapy. The correct sequence for a functional β-subunit could be inserted into the photoreceptors to replace the mutant gene. This could then enable the cells to produce a functional cGMP PDE and allow them to respond to light accordingly. However, the biggest challenge will be detecting the mutation before it’s too far gone. As seen in figure 1, the differentiation of the retina takes a number of days, and would make it difficult to distinguish between abnormal development and the destruction of photoreceptors. If detected too late, the photoreceptors will have already been destroyed and gene therapy will have no
The Structure of the Mouse Retina
Introduction
Retinitis Pigmentosa (RP) is a genetic disorder that results in the degradation of photoreceptors in the retina. This leads to difficulties with night vision, reduced peripheral vision and eventually the complete loss of visual activity. It’s inherited as an autosomal dominant, autosomal recessive, as well as an X-linked trait. A small percentage of people with this disorder have a mutation in the gene that codes for the β-subunit of the enzyme phosphodiesterase (PDE). To further understand the nature of this disease, we studied rd1 mice. These animals also have a mutation in the gene that codes for the β-subunit of PDE, leading to the degeneration of photoreceptors …show more content…
The rd1 mouse shows severe degeneration of photoreceptors with the pigmented epithelial cells collapsing in on the inner nuclear layer.
Discussion By comparing the wild type with the rd1 mouse, it’s clear that not all cell types are destroyed. Only the photoreceptors are degraded, whilst the other cell types are preserved. We can therefore conclude that the retinal degeneration mutation only effects the expression of the photoreceptors. Without the β-subunit of PDE, the photoreceptors are unable to break down cGMP, and therefore unable to close their sodium ion channels, allowing the receptors to continue firing even in the presence of light. This means that they cannot respond to any light stimulus, and are degraded as a consequence. Using these results we could potentially find a way to cure blindness in humans with similar retinal degeneration mutations. Since we’ve deduced that the loss of visual activity is solely due to the lack of the β-subunit of PDE in rd1 mice, we need to find a way of correcting/replacing the mutation so the cells can produce functional PDEs. This could potentially be achieved through continuous gene therapy. The correct sequence for a functional β-subunit could be inserted into the photoreceptors to replace the mutant gene. This could then enable the cells to produce a functional cGMP PDE and allow them to respond to light accordingly. However, the biggest challenge will be detecting the mutation before it’s too far gone. As seen in figure 1, the differentiation of the retina takes a number of days, and would make it difficult to distinguish between abnormal development and the destruction of photoreceptors. If detected too late, the photoreceptors will have already been destroyed and gene therapy will have no