This project had several aims focusing on understanding cell death in normal and an animal model of Retinitis Pigmentosa (P23H) rat. It supports an Health Research Council of New Zealand grant.
Project Results and Impact
We studied the changes in both normal retinas and animal models of retinal degeneration (RD) to understand how the disease affects the structure and chemical communication in the retina.
- In normal mouse retinas, we identified the ages at which cells communicate with each other using neurotransmitters. This helped us understand changes in abnormal retinas affected by RD.
- RD causes both structural and chemical remodeling in the retina. The anatomy and chemical composition of the retina change, making interventions like cell transplants or implants challenging.
- We mapped out the neurochemical communication between cells in RD retinas, identifying unique neurotransmitter receptors in different types of retinal cells. These receptors are crucial for cells to communicate with each other.
- In an animal model of RD (rd/rd mouse), we found early loss of cell types and altered neurochemical development and receptor expression. This discovery has important implications for potential intervention measures, as there is a critical period during which modifications can be made.
- Excessive light damage can accelerate retinal degeneration. We investigated this in normal retinas and an RD animal model, focusing on understanding the mechanisms of cell death.
- We found that photoreceptor cell death in RD occurs through two mechanisms: excessive entry of ions into cells and programmed cell death (apoptosis). Therapeutic strategies should target both ion flow regulation and the apoptotic pathway to slow down cell death.
- We collaborated with Dr. Fletcher and performed pharmacological interventions in our RD model, successfully delaying the degeneration. Further analysis of these results is underway and will be reported in the future.
In summary, our research has identified the optimal time for intervention in retinal degeneration and has shown that light exposure can accelerate photoreceptor death, while pharmacological interventions can slow it down. Understanding the changes in the structure and chemical communication of the retina in RD is crucial for developing effective treatments.
Published 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 Impact factor = 4.6500
- 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 Impact factor = 3.4700
- CHUA J, FLETCHER EL, KALLONIATIS M. 2008. Functional remodeling of glutamate receptors by inner retinal neutrons occurs from an early stage of retinal degeneration. JOURNAL OF COMPARATIVE NEUROLOGY. (SUBMITTED) Impact factor = 3.4700
Professor Michael Kalloniatis
University of Auckland
Dr Monica Acosta, University of Auckland, New Zealand
Dr Keely Bumstead O’Brien, University of Melbourne
Dr Brendan O’Brien, St Vincent’s Neuroscience, Melbourne
Dr Erica Fletcher, University of Melbourne