By Adrian Galbreth
A new stress pathway has been identified as a potential therapeutic target to prevent vision loss in people who have eye damage, which could give hope to thousands of people around the planet.
New research carried out by the Children's Hospital and Harvard Medical School and published by Cell Press in the journal Neuron has identified specific cell-stress signaling pathways that link injury of the optic nerve with irreversible vision loss.
Experts claim the research may lead to new strategies that will help to protect vulnerable neurons in the retina after optic nerve damage and diseases.
Senior study author Dr Zhigang He explained how retinal ganglion cells (RGCs) send visual information from the retina to the brain through long processes called axons, which are bundled together to form the optic nerve.
"RGCs are highly vulnerable when then optic nerve is damaged. For example, optic nerve injury and subsequent loss of RGCs occur often in the setting of head injury and other types of retinal pathology, such as glaucoma," he added.
Previous studies have linked a cell-death pathway called apoptosis with trauma-related RGC death, but the problem was that targeting apoptosis is not considered an efficient therapeutic strategy, as apoptosis is likely to be one of the last steps in the disease process.
In the new study, Dr He and colleagues used an optic nerve crush model to investigate signals that are farther upstream of RGC death, with the researchers discovering that optic nerve crush led to activation of distinct pathways of the unfolded protein response (UPR).
The experts noted that UPR is a cellular stress response that can be protective in some cell types, and revealed that the pathways are activated by axon injury.
The way these pathways function in neurons may be quite different from other cell types, according to the specialists, who suggested that axonal damage results in pro-cell-death UPR activation, which could contribute to irreversible cell death associated with optic nerve injury and eye conditions such as glaucoma.
An important aspect of this, according to Dr He, is that such differential activations of UPR pathways and their distinct effects on neuronal cell death are also observed in RGCs with other types of axonal insults, such as intraocular pressure elevation.
"This suggests a new protective strategy for optic nerve injury and diseases. In addition, as axonal damage is common in different neurodegenerative diseases, it would be interesting to see whether what we learned from optic nerve injury models is applicable to other types of neurodegeneration," he explained.
Further studies will now be carried out to determine whether the therapeutic target could be rolled out on a large scale to prevent vision loss in the thousands of people around the world who have optic nerve injury or eye diseases such as glaucoma.
It is the latest in a series of studies which give hope to people across the planet who suffer from, or at risk of, eye disease.
Recently, research carried out by experts at the University of Pennsylvania has suggested that they can prevent, or even reverse, the blinding retinal disease retinitis pigmentosa, which is hereditary and affects thousands of people around the world.
Researchers working on the gene therapy approach took advantage of a viral vector to deliver the therapeutic RPGR gene specifically to diseased rods and cones in rods, which normally malfunction and progressively die in the absence of treatment.
After the dogs' recovery was assessed using a variety of methods that are used clinically in patients, such as electroretinography and optical coherence tomography, the scientists concluded that the results are promising and relevant for translation to the clinic.
by Martin Burns