Deferiprone Protects against Photoreceptor Degeneration Induced by Tunicamycin in the Rat Retina

被引:11
作者
Shirai, Yousuke [1 ]
Mori, Asami [1 ]
Nakahara, Tsutomu [1 ]
Sakamoto, Kenji [1 ]
Ishii, Kunio [1 ]
机构
[1] Kitasato Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol, Minato Ku, Tokyo 1088641, Japan
关键词
deferiprone; tunicamycin; endoplasmic reticulum stress; iron chelation; ENDOPLASMIC-RETICULUM STRESS; BLOOD-BRAIN-BARRIER; NEURONAL CELL-DEATH; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; IRON CHELATOR; NEUROPROTECTION; DESFERRIOXAMINE; PROSPECTS; ACID;
D O I
10.1248/bpb.b15-00185
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Endoplasmic reticulum stress has been reported to be involved in the pathogenesis of retinitis pigmentosa, macular degeneration and diabetic retinopathy. In the present study, we examined the effects of deferiprone, an iron chelator, on photoreceptor degeneration induced by tunicamycin (300 nmol/eye), an endoplasmic reticulum stress inducer, in the rat retina. Scotopic electroretinogram measurement and morphometric evaluation were done 7d after the injection of tunicamycin. In the scotopic electroretinogram, intravitreal deferiprone (5 nmol/eye) injected simultaneously with tunicamycin significantly reduced the decreases in a- and b-wave amplitudes induced by tunicamycin. Morphometric evaluation showed that deferiprone significantly reduced thinning of the outer nuclear layer, the inner segment and the outer segment. These results suggest that iron chelation therapy may be a good candidate for the treatment of eye diseases related to endoplasmic reticulum stress.
引用
收藏
页码:1076 / 1080
页数:5
相关论文
共 36 条
[1]   A pilot trial of deferiprone for neurodegeneration with brain iron accumulation [J].
Abbruzzese, Giovanni ;
Cossu, Giovanni ;
Balocco, Manuela ;
Marchese, Roberta ;
Murgia, Daniela ;
Melis, Maurizio ;
Galanello, Renzo ;
Barella, Susanna ;
Matta, Gildo ;
Ruffinengo, Uberto ;
Bonuccelli, Ubaldo ;
Forni, Gian Luca .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2011, 96 (11) :1708-1711
[2]   TUNICAMYCIN-INDUCED DEGENERATION IN CONE PHOTORECEPTORS [J].
ANDERSON, DH ;
WILLIAMS, DS ;
NEITZ, J ;
FARISS, RN ;
FLIESLER, SJ .
VISUAL NEUROSCIENCE, 1988, 1 (02) :153-158
[3]   Neurodegenerative diseases and oxidative stress [J].
Barnham, KJ ;
Masters, CL ;
Bush, AI .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (03) :205-214
[4]   Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lession in rats [J].
Ben Shachar, D ;
Kahana, N ;
Kampel, V ;
Warshawsky, A ;
Youdim, MBH .
NEUROPHARMACOLOGY, 2004, 46 (02) :254-263
[5]  
Berkowitz BA, 1998, INVEST OPHTH VIS SCI, V39, P391
[6]   Effect of desferrioxamine and deferiprone (L1) on the proliferation of MG-63 bone cells and on phosphatase alkaline activity [J].
Diaz, MLN ;
Elorriaga, R ;
Canteros, A ;
Andia, JBC .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 1998, 13 :23-28
[7]   Quantitative analysis of intravitreal injections in the rat [J].
Dureau, P ;
Bonnel, S ;
Menasche, M ;
Dufier, JL ;
Abitbol, M .
CURRENT EYE RESEARCH, 2001, 22 (01) :74-77
[8]   PHOTORECEPTOR-SPECIFIC DEGENERATION CAUSED BY TUNICAMYCIN [J].
FLIESLER, SJ ;
RAPP, LM ;
HOLLYFIELD, JG .
NATURE, 1984, 311 (5986) :575-577
[9]   The pharmacokinetics and blood-brain barrier permeation of the chelators 1,2-dimethyl-, 1,2-diethyl-, and 1-[ethan-1'ol]-2-methyl-3-hydroxypyridin-4-one in the rat [J].
Fredenburg, AM ;
Sethi, RK ;
Allen, DD ;
Yokel, RA .
TOXICOLOGY, 1996, 108 (03) :191-199
[10]  
Gorbatyuk M, 2013, MOL VIS, V19, P1985