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Preventing retinal apoptosis--is there a common therapeutic theme?
Francesca Doonan1, Gillian Groeger, Thomas G Cotter
1Biochemistry Department, Biosciences Research Institute, University College Cork, Cork, Ireland.
Abstract:
There is an urgent need for therapies for retinal diseases; retinitis pigmentosa sufferers have no treatment options available and those targeted at other retinopathies have shown limited effectiveness. The process of programmed cell death or apoptosis although complex, remains a possible target for the treatment of retinal diseases. Having identified apoptosis in the vertebrate retina in populations of immature neurons as an essential part of development it was proposed that re-activation of these developmental cell death pathways might provide insight into the death mechanisms operating in retinal diseases. However, the discovery that numerous factors initiate and mediate the apoptotic cascade in mature photoreceptors has resulted in a relatively untargeted approach to examining and arresting apoptosis in the retina. In the last 5 years, mouse models have been treated with a diverse range of drugs or factors including anti-oxidants, growth factors, steroid hormones, calcium/calpain inhibitors and tetracycline antibiotics. Therefore to draw a unifying theme from these broad research areas is challenging. However, this review focusses on two targets which are currently under investigation, reactive oxygen species and mammalian target of rapamycin, drawing together the common themes of these research areas.
Insights
Developing new therapies for retinal diseases is crucial. This review focuses on reactive oxygen species and the mammalian target of rapamycin pathway as potential targets to treat retinal conditions like retinitis pigmentosa.
Area of Science:
- Ophthalmology
- Cell Biology
- Neuroscience
Background:
- Retinal diseases lack effective treatments, with retinitis pigmentosa patients having no options.
- Apoptosis (programmed cell death) is a complex but potential therapeutic target for retinal diseases.
- Previous research on photoreceptor apoptosis has been broad, making a unified approach challenging.
Purpose of the Study:
- To review current research on therapeutic targets for retinal diseases.
- To explore the roles of reactive oxygen species and mammalian target of rapamycin in retinal apoptosis.
- To identify common themes in the investigation of these two targets.
Main Methods:
- Literature review of recent studies on retinal disease therapies.
- Focus on research investigating reactive oxygen species and mTOR pathways.
- Analysis of therapeutic interventions in mouse models of retinal disease.
Main Results:
- Numerous factors initiate and mediate apoptosis in mature photoreceptors.
- Diverse drugs and factors have been tested in mouse models, including antioxidants and growth factors.
- Reactive oxygen species and mTOR are key targets currently under investigation.
Conclusions:
- Targeting apoptosis pathways offers a potential strategy for treating retinal diseases.
- Further research into reactive oxygen species and mTOR may yield effective therapies.
- A unified approach is needed to advance treatment options for conditions like retinitis pigmentosa.
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