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Volume 9, Issue 2, Pages (February 2004)

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Presentation on theme: "Volume 9, Issue 2, Pages (February 2004)"— Presentation transcript:

1 Volume 9, Issue 2, Pages 173-181 (February 2004)
Antioxidant Gene Therapy Can Protect Hearing and Hair Cells from Ototoxicity  Kohei Kawamoto, Su-Hua Sha, Ryosei Minoda, Masahiko Izumikawa, Hiromichi Kuriyama, Jochen Schacht, Yehoash Raphael  Molecular Therapy  Volume 9, Issue 2, Pages (February 2004) DOI: /j.ymthe Copyright © 2003 The American Society of Gene Therapy Terms and Conditions

2 Fig. 1 Phalloidin-stained whole mounts of basal cochlear turns. (a) Ad.cat-inoculated cochlea with well-preserved inner (arrow) and outer hair cells (arrowheads). (b) Contralateral ear of (a) with outer hair cells entirely absent, replaced by scars (arrowheads). Inner hair cells are intact. (c) Ad.SOD1-inoculated cochlea with nearly normal outer hair cell population and a full complement of inner hair cells. (d) The contralateral cochlea of (c) in Ad.SOD1-treated guinea pig showing a complete destruction of outer hair cells. (e) Ad.SOD2-treated left cochlea with a normal organ of Corti. (f) The contralateral cochlea of the Ad.SOD2 animals with a complete loss of outer hair cells. (g) Ad.null-inoculated ear showing extensive damage to the organ of Corti with a complete loss of outer hair cells. (h) The contralateral ear in a guinea pig receiving Ad.null showing a severe cochlear lesion in the outer hair cell area. Bar, 25 μm. Molecular Therapy 2004 9, DOI: ( /j.ymthe ) Copyright © 2003 The American Society of Gene Therapy Terms and Conditions

3 Fig. 2 Averaged cytocochleograms for experimental (left ear, a, c, e, g, i) and control (right ear, b, d, f, h, j) groups. The percentage of missing hair cells is plotted as a function of the location in the cochlea (distance from the apex). (a, b) Percentage of missing outer hair cells in the Ad.cat-inoculated ears (a) is less than that of contralateral ears (b). (c, d) Ad.SOD1-treated ears (c) show better hair cell preservation in the very base of the cochlea than the contralateral controls (d). (e, f) The extent of hair cell loss in Ad.SOD2-treated ears (e) is less than in the contralateral ears (f). (g–j) Ad.null- and AP-inoculated ears (g and i, respectively) show cytocochleograms similar to those of their contralateral ears (h, j) and the contralateral ears of experimental groups (b, d, f). Molecular Therapy 2004 9, DOI: ( /j.ymthe ) Copyright © 2003 The American Society of Gene Therapy Terms and Conditions

4 Fig. 3 The percentage loss of outer hair cells averaged in the three outer hair cell rows (mean ± SD) in the inoculated ears of each of the five groups. Outer hair cell loss in each of the three experimental groups is approximately 20%, whereas in control groups it is 40%. *The difference between experimental and control groups is statistically significant (P < 0.01). Molecular Therapy 2004 9, DOI: ( /j.ymthe ) Copyright © 2003 The American Society of Gene Therapy Terms and Conditions

5 Fig. 4 ABR threshold shifts (mean ± SD) at each tested frequency in the five groups. (a) In Ad.cat-inoculated animals, significant differences are detected at all three frequencies. (b) Ad.SOD1-inoculated animals show no statistical differences between inoculated and contralateral ears at all tested frequencies. (c) Ad.SOD2-inoculated animals show significant differences at 12 and 20 kHz. (d) Ad.null- and (e) AP-inoculated animals showed no significant differences between inoculated ears and contralateral ears (P < 0.05). Molecular Therapy 2004 9, DOI: ( /j.ymthe ) Copyright © 2003 The American Society of Gene Therapy Terms and Conditions

6 Fig. 5 Enzymatic activities of (A) catalase and (B) SOD2 following Ad.cat and Ad.SOD2 inoculation, respectively. (A) Catalase activity in the Ad.cat-inoculated ears (n = 9) is significantly increased compared to contralateral ears (n = 9) and Ad.null ears (n = 9) by paired t test (P < 0.01). Ad.null-inoculated ears (n = 9) display 95 ± 27 units/mg protein, similar to Ad.cat contralateral ears (100 ± 54 units/mg protein). (B) SOD2 activity in the Ad.SOD2-inoculated ears (n = 5) differs from activity in the contralateral ears (n = 5), P < by paired t test. Ad.null-inoculated ears ( units/mg protein, n = 5) are not different from the Ad.cat contralateral ears (1.7 ± 1.6 units/mg protein, n = 5). Molecular Therapy 2004 9, DOI: ( /j.ymthe ) Copyright © 2003 The American Society of Gene Therapy Terms and Conditions


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