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Henri Olavi Leinonen, Symantas Ragauskas, Jooseppi Puranen, Adrian Smedowski, Kari Airenne, Seppo Ylä-Herttuala, Heikki Tanila, Giedrius Kalesnykas; Heat shock protein 25 kDa gene therapy alleviates retinal ganglion cell dysfunction after optic nerve crush in mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6195.
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Heat shock proteins (HSPs) are molecular helper proteins, chaperones, which are known to be induced after various forms of chemical and environmental insults. HSP expression is upregulated in retinal neurons and glial cells in experimental glaucoma, cerebral ischemia and hypoperfusion models. Thus, we asked the question whether HSP25 gene therapy could prevent retinal ganglion cell (RGC) dysfunction after optic nerve crush (ONC) which is known to cause retrograde damage to RGCs.
Serotype 2 recombinant adeno-associated viral vectors encoding HSP25 were intravitreously, unilaterally, injected three months before the optic nerve crush into C57Bl/6J mice. The control group of mice received saline injections. ONC was performed to the same eye as injections. Electroretinography (ERG) was performed 30 days after ONC in response to patterned (pERG) and flash stimuli (fERG). After ERG recordings, the animals were deeply anesthetized and perfused. The eyes and optic nerves were collected for morphological analysis.
As expected, ONC strongly decreased pERG responses without affecting fERG. However, virus-injected eyes preserved approximately 60% better function compared to saline-injected controls as measured with pERG amplitude. No other statistically significant differences in other analyzed amplitude parameters were found. Currently, we are performing morphological analysis with the collected retinas and optic nerves.
HSP25 gene therapy alleviates retinal function deficit after ONC. Our preliminary results suggest that specific HSP induction might serve as a novel treatment strategy for optic neuropathies.
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