title: Modulation of the expression of the transcription factor Max in rat retinal ganglion cells by a recombinant adeno-associated viral vector.
abstract: Exclusion of the transcription factor Max from the nucleus of retinal ganglion cells is an early, caspase-independent event of programmed cell death following damage to the optic axons. To test whether the loss of nuclear Max leads to a reduction in neuroprotection, we developed a procedure to overexpress Max protein in rat retinal tissue in vivo. A recombinant adeno-associated viral vector (rAAV) containing the max gene was constructed, and its efficiency was confirmed by transduction of HEK-293 cells. Retinal ganglion cells were accessed in vivo through intravitreal injections of the vector in rats. Overexpression of Max in ganglion cells was detected by immunohistochemistry at 2 weeks following rAAV injection. In retinal explants, the preparation of which causes damage to the optic axons, Max immunoreactivity was increased after 30 h in vitro, and correlated with the preservation of a healthy morphology in ganglion cells. The data show that the rAAV vector efficiently expresses Max in mammalian retinal ganglion cells, and support the hypothesis that the Max protein plays a protective role for retinal neurons.
authors.affiliation: Instituto de Biofísica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. petrs@biof.ufrj.br
authors.forename: H
authors.initials: H
authors.lastname: Petrs-Silva
authors.forename: V
authors.initials: V
authors.lastname: Chiodo
authors.forename: L B
authors.initials: LB
authors.lastname: Chiarini
authors.forename: W W
authors.initials: WW
authors.lastname: Hauswirth
authors.forename: R
authors.initials: R
authors.lastname: Linden
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000378:metabolism; D010321:Parvoviridae; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499329:Max protein, rat; D011994:Recombinant Proteins