PMID:18191123

Citation	Yaung, J, Kannan, R, Wawrousek, EF, Spee, C, Sreekumar, PG and Hinton, DR (2008) Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia. Exp. Eye Res. 86:355-65
Abstract	This study evaluated the role of crystallins in retinal degeneration induced by chemical hypoxia. Wild-type, alphaA-crystallin (-/-), and alphaB-crystallin (-/-) mice received intravitreal injection of 12 nmol (low dose), 33 nmol (intermediate dose) or 60 nmol (high dose) cobalt chloride (CoCl(2)). Hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) stains were performed after 24 h, 96 h, and 1 week post-injection, while immunofluorescent stains for alphaA- and alphaB-crystallin were performed 1 week post-injection. The in vitro effects of CoCl(2) on alphaB-crystallin expression in ARPE-19 cells were determined by real time RT-PCR, Western blot, and confocal microscopy and studies evaluating subcellular distribution of alphaB-crystallin in the mitochondria and cytosol were also performed. Histologic studies revealed progressive retinal degeneration with CoCl(2) injection in wild-type mice. Retinas of CoCl(2) injected mice showed transient increased expression of HIF-1alpha which was maximal 24h after injection. Intermediate-dose CoCl(2) injection was associated with increased retinal immunofluorescence for both alphaA- and alphaB-crystallin; however, after high-dose injection, increased retinal degeneration was associated with decreased levels of crystallin expression. Injection of CoCl(2) at either intermediate or high dose in alphaA-crystallin (-/-) and alphaB-crystallin (-/-) mice resulted in much more severe retinal degeneration compared to wild-type eyes. A decrease in ARPE-19 total and cytosolic alphaB-crystallin expression with increasing CoCl(2) treatment and an increase in mitochondrial alphaB-crystallin were found. We conclude that lack of alpha-crystallins accentuates retinal degeneration in chemically induced hypoxia in vivo.
Links	PubMed PMC2731668 Online version:10.1016/j.exer.2007.11.007
Keywords	Animals; Apoptosis; Cells, Cultured; Disease Models, Animal; Disease Progression; Mice; Mice, Knockout; Mitochondria/metabolism; Pigment Epithelium of Eye/metabolism; Pigment Epithelium of Eye/pathology; Retinal Degeneration/chemically induced; Retinal Degeneration/metabolism; Retinal Degeneration/pathology; Reverse Transcriptase Polymerase Chain Reaction/methods; alpha-Crystallin B Chain/genetics; alpha-Crystallin B Chain/metabolism; alpha-Crystallins/deficiency; alpha-Crystallins/genetics; alpha-Crystallins/physiology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CRYAB	located_in	GO:0005829: cytosol	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:CRYAB	located_in	GO:0005739: mitochondrion	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:CRYAA	acts_upstream_of_or_within	GO:0001666: response to hypoxia	ECO:0000315: mutant phenotype evidence used in manual assertion	MGI:MGI:1858025	P		Seeded From UniProt	complete
MOUSE:CRYAA	acts_upstream_of_or_within	GO:0043066: negative regulation of apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion	MGI:MGI:1858025	P		Seeded From UniProt	complete
MOUSE:CRYAB	acts_upstream_of_or_within	GO:0043066: negative regulation of apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion	MGI:MGI:2652177	P		Seeded From UniProt	complete
MOUSE:CRYAB	part_of	GO:0005829: cytosol	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:CRYAB	part_of	GO:0005739: mitochondrion	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:CRYAB	acts_upstream_of_or_within	GO:0001666: response to hypoxia	ECO:0000315: mutant phenotype evidence used in manual assertion	MGI:MGI:2652177	P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.