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- Title
AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.
- Authors
Kwong, J M K; Gu, L; Nassiri, N; Bekerman, V; Kumar-Singh, R; Rhee, K D; Yang, X-J; Hauswirth, W W; Caprioli, J; Piri, N
- Abstract
We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul−1) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies.
- Subjects
PHARMACOLOGY; HEAT shock proteins; GENE expression; RETINAL ganglion cells; AXONS; COMPARATIVE studies; WOUNDS &; injuries
- Publication
Gene Therapy, 2015, Vol 22, Issue 2, p138
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/gt.2014.105