1. AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.
- Author
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Kwong, JMK, Gu, L, Nassiri, N, Bekerman, V, Kumar-Singh, R, Rhee, KD, Yang, X-J, Hauswirth, WW, Caprioli, J, and Piri, N
- Subjects
Axons ,Retinal Ganglion Cells ,Retina ,Animals ,Mice ,Inbred C57BL ,Humans ,Dependovirus ,Optic Nerve Injuries ,Lactams ,Macrocyclic ,Benzoquinones ,Combined Modality Therapy ,Nerve Crush ,Transduction ,Genetic ,Nerve Regeneration ,Cell Survival ,HSP70 Heat-Shock Proteins ,Transcriptional Activation ,Genetic Therapy ,Physical Injury - Accidents and Adverse Effects ,Neurosciences ,Eye Disease and Disorders of Vision ,Neurodegenerative ,Eye ,Biological Sciences ,Medical and Health Sciences ,Biotechnology - 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.
- Published
- 2015