Abnormal metal levels in the primary visual pathway of the DBA/2J mouse model of glaucoma

被引:19
作者
DeToma, Alaina S. [1 ]
Dengler-Crish, Christine M. [2 ]
Deb, Aniruddha [1 ,3 ]
Braymer, Joseph J. [1 ]
Penner-Hahn, James E. [1 ,4 ]
Schyf, Cornelis J. van der [2 ]
Lim, Mi Hee [1 ,5 ,6 ]
Crish, Samuel D. [2 ]
机构
[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[2] Northeast Ohio Med Univ NEOMED, Dept Pharmaceut Sci, Rootstown, OH USA
[3] Michigan Mem Phoenix Energy Inst, Ann Arbor, MI USA
[4] Univ Michigan, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA
[6] Ulsan Natl Inst Sci & Technol UNIST, Dept Chem, Ulsan 689798, South Korea
关键词
Superior colliculus; Retina; ICP-MS; Neurodegeneration; Glaucoma; GANGLION-CELL DEGENERATION; ALZHEIMERS-DISEASE; MICROARRAY ANALYSIS; GENE-EXPRESSION; AQUEOUS-HUMOR; AMYLOID-BETA; IRON; NEURODEGENERATION; SYNAPSE; RETINA;
D O I
10.1007/s10534-014-9790-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The purpose of this study was to determine metal ion levels in central visual system structures of the DBA/2J mouse model of glaucoma. We used inductively coupled plasma mass spectrometry (ICP-MS) to measure levels of iron (Fe), copper (Cu), zinc (Zn), magnesium (Mg), manganese (Mn), and calcium (Ca) in the retina and retinal projection of 5-month (pre-glaucomatous) and 10-month (glaucomatous) old DBA/2J mice and age-matched C57BL/6J controls. We used microbeam X-ray fluorescence (mu-XRF) spectrometry to determine the spatial distribution of Fe, Zn, and Cu in the superior colliculus (SC), which is the major retinal target in rodents and one of the earliest sites of pathology in the DBA/2J mouse. Our ICP-MS experiments showed that glaucomatous DBA/2J had lower retinal Fe concentrations than pre-glaucomatous DBA/2J and age-matched C57BL/6J mice. Pre-glaucomatous DBA/2J retina had greater Mg, Ca, and Zn concentrations than glaucomatous DBA/2J and greater Mg and Ca than age-matched controls. Retinal Mn levels were significantly deficient in glaucomatous DBA/2J mice compared to aged-matched C57BL/6J and pre-glaucomatous DBA/2J mice. Regardless of age, the SC of C57BL/6J mice contained greater Fe, Mg, Mn, and Zn concentrations than the SC of DBA/2J mice. Greater Fe concentrations were measured by mu-XRF in both the superficial and deep SC of C57BL/6J mice than in DBA/2J mice. For the first time, we show direct measurement of metal concentrations in central visual system structures affected in glaucoma and present evidence for strain-related differences in metal content that may be specific to glaucomatous pathology.
引用
收藏
页码:1291 / 1301
页数:11
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