Gene therapy may prove successful in treating retinal
an attempt to improve the prognosis of patients suffering retinal
detachment, researchers in Taiwan and the US have developed an entirely
novel method to extend the activity of the retina's photoreceptor
Led by Wei-Chu Wu MD and Yeou-Ping Tsao MD, the research team has
succeeded in delivering a modified virus containing the gene for
neurotrophic growth factor to the retinas of experimental rats with
a retinal detachment similar to that found in human patients.
of neurotrophic growth factor
The neurotrophic growth factor essentially represents a positive
molecular signal and a protective agent which encourages photoreceptor
The results showed that animals receiving the therapy had five times
higher neurotrophic growth factor levels, about 61% thicker outer
segments and five times less cell death in the retina.
The researchers, based at the Department of Ophthalmology, Chang
Guan Memorial Hospital, Taiwan and at the Department of Molecular
Genetics and Biochemistry, University of Pittsburgh, US injected
rat eyes with about 11 billion viral particles three weeks before
inducing retinal detachment.
Once retinal detachment had been induced, the researchers monitored
the effect of the therapy when compared to controls.
Researchers focused their analyses on three readouts: the quantity
of neurotrophic growth factor expressed in the retina; the thickness
of the various cellular layers that make up the retina; and the
degree of cell loss encountered in eyes.
The research team showed that the factor was expressed at a mean
level of 377.71 picograms per millilitre in treated eyes compared
to a mean level of 67.86 picograms per millilitre in the control
eyes - a five-fold difference.
gene delivery and expression
This finding clearly demonstrates the successful delivery and expression
of the therapeutic gene to the retina.
Following this, the researchers measured the thickness of the outer
segment to determine whether there was increased cell density in
the retina, which would be expected if the neurotrophic factor was
to impart a positive effect.
In a comparison between controls and treated eyes, the researchers
observed after 28 days a mean thickness of 10.78 micrometres in
the treated eyes versus a mean thickness of 4.01 micrometres in
the control eyes - a 61% difference.
lower rate of cell death
Finally, the researchers examined the degree of cell death occurring
in the retina following retinal detachment. Those results showed
a similarly positive outcome.
The treated eyes had a mean level of 5.40 dead cells per 250 micrometres
of retina; the control eyes had a mean level of 26.2 dead cells
per 250 micrometres.
Clearly, the researchers demonstrated a significant reduction in
photoreceptor cell loss following this gene therapy approach.
Although such treatments will inevitably have a number of limitations
and obstacles before a human clinical trial can be conceived, it
nevertheless proves the efficacy of such a system in improving the
prognosis for retinal detachment exemplified in the experimental
Gene therapy is most certainly a bumpy ride and the current data
provides real promise of this biological approach to dealing with
a large array of diverse disorders.
The real challenge now lies in the capacity for the scientific,
medical and business communities to transfer such benefits out of
the laboratory and into the clinic.
Gearóid Tuohy is a post-doctural researcher in the molecular
genetics of retinopathies at the Smurfit Institute of Genetics,
Trinity College, Dublin, Ireland.
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