Photoreceptor degeneration in retinitis pigmentosa

Project Aim

The aim of this project was to study the structure and chemical processes in the retinas of mice to understand how they change when the retina begins to break down. Special attention was made to when these changes happened over time. Additionally, investigation was made into how too much light can speed up cell death in the retina and whether certain medications could slow down this damage in retinal diseases.

Project Summary

In this study, both normal and genetically modified mice with a condition called retinitis pigmentosa, were examined.

The cells in a healthy retina were mapped to see how they communicate with each other and when this process begins in normal mice. This was compared to mice suffering from retinal degeneration and it was found that their retinal structure and communication pathways were significantly altered. This finding shows that when retinal degeneration is advanced, treatments like transplants or gene therapy become much harder.
While scientists have known about the structural changes in retinal degeneration, this study was the first to show how cell communication is affected. Specific receptors were identified in the cells that allow them to communicate, and it was found that in retinal degeneration, these receptors can disappear, making it difficult for the cells to function properly. A “critical period” was also discovered —a window of time where treatment might be possible because these receptors are still present. After this period, however, it becomes much harder to intervene as the changes become too advanced.
How exposure to too much light speeds up retinal damage was also examined. It was found that this happens in two ways: through unregulated ion flow into the cells and programmed cell death (apoptosis). These findings suggest that any potential treatments should target both of these processes. Medications that might slow down retinal degeneration were also tested, though the results of this are still being analysed.

Peer reviewed articles

Yu Ty, Acosta ML, Ready S, Cheong YL, Kalloniatis M, 2007. Light exposure causes functional changes in the retina: increased photoreceptors cation channel permeability, photoreceptor apoptosis and altered retinal metabolic function. Journal of Neurochemistry. 103: 714-724.
Acosta ML, Chua J, Kalloniatis M, 2007. Functional activation of glutamate ionotropic receptors in the developing mouse retina. Journal of Comparative Neurology. 500(5) : 923-941.
Chua J, Fletcher EL, Kalloniatis M, 2009. Functional remodeling of glutamate receptors by inner retinal neurons occurs from an early stage of retinal degeneration. Journal of Comparative Neurology. 514 (5), 473-491.

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