title: AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.
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.
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: J M K
authors.initials: JM
authors.lastname: Kwong
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Gu
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Nassiri
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Bekerman
authors.affiliation: Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kumar-Singh
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Rhee
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, University of Florida, Gainesville, FL, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Hauswirth
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Caprioli
authors.affiliation: Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Piri
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D016227:Benzoquinones / Q000494:pharmacology*; D002470:Cell Survival; D003131:Combined Modality Therapy; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009409:Nerve Crush; D009416:Nerve Regeneration; D020221:Optic Nerve Injuries / Q000628:therapy*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000502:physiology*; D015533:Transcriptional Activation; D014161:Transduction, Genetic
chemical_list: D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin