Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Invest Ophthalmol Vis Sci
2015 Dec 01;5613:7947-55. doi: 10.1167/iovs.15-16799.
Show Gene links
Show Anatomy links
Light Induces Ultrastructural Changes in Rod Outer and Inner Segments, Including Autophagy, in a Transgenic Xenopus laevis P23H Rhodopsin Model of Retinitis Pigmentosa.
???displayArticle.abstract???
We previously reported a transgenic Xenopus laevis model of retinitis pigmentosa in which tadpoles express the bovine form of P23H rhodopsin (bP23H) in rod photoreceptors. In this model, retinal degeneration was dependent on light exposure. Here, we investigated ultrastructural changes that occurred in the rod photoreceptors of these retinas when exposed to light. Tadpoles expressing bP23H in rods were transferred from constant darkness to a 12-hour light:12-hour dark (12L:12D) regimen. For comparison, transgenic tadpoles expressing an inducible form of caspase 9 (iCasp9) were reared in a 12L:12D regimen, and retinal degeneration was induced by administration of the drug AP20187. Tadpoles were euthanized at various time points, and eyes were processed for confocal light and transmission electron microscopy. We observed defects in outer and inner segments of rods expressing bP23H that were aggravated by light exposure. Rod outer segments exhibited vesiculations throughout and were rapidly phagocytosed by the retinal pigment epithelium. In rod inner segments, we observed autophagic compartments adjacent to the endoplasmic reticulum and extensive vesiculation at later time points. These defects were not found in rods expressing iCasp9, which completely degenerated within 36 hours after drug administration. Our results indicate that ultrastructural defects in outer and inner segment membranes of bP23H expressing rods differ from those observed in drug-induced apoptosis. We suggest that light-induced retinal degeneration caused by P23H rhodopsin occurs via cell death with autophagy, which may represent an attempt to eliminate the mutant rhodopsin and/or damaged cellular compartments from the secretory pathway.
Adamus,
Anti-rhodopsin monoclonal antibodies of defined specificity: characterization and application.
1991, Pubmed
Adamus,
Anti-rhodopsin monoclonal antibodies of defined specificity: characterization and application.
1991,
Pubmed
Arango-Gonzalez,
Identification of a common non-apoptotic cell death mechanism in hereditary retinal degeneration.
2014,
Pubmed
ASHFORD,
Cytoplasmic components in hepatic cell lysosomes.
1962,
Pubmed
Calvert,
Light-driven translocation of signaling proteins in vertebrate photoreceptors.
2006,
Pubmed
Chiang,
Selective activation of ATF6 and PERK endoplasmic reticulum stress signaling pathways prevent mutant rhodopsin accumulation.
2012,
Pubmed
Chiang,
Robust Endoplasmic Reticulum-Associated Degradation of Rhodopsin Precedes Retinal Degeneration.
2015,
Pubmed
Chiang,
IRE1 directs proteasomal and lysosomal degradation of misfolded rhodopsin.
2012,
Pubmed
Corrochano,
α-Synuclein levels affect autophagosome numbers in vivo and modulate Huntington disease pathology.
2012,
Pubmed
Deter,
Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes.
1967,
Pubmed
Dryja,
A point mutation of the rhodopsin gene in one form of retinitis pigmentosa.
1990,
Pubmed
Eskelinen,
To be or not to be? Examples of incorrect identification of autophagic compartments in conventional transmission electron microscopy of mammalian cells.
2008,
Pubmed
Gorbatyuk,
Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78.
2010,
Pubmed
Guimarães,
Alternative programs of cell death in developing retinal tissue.
2003,
Pubmed
Haeri,
Rhodopsin mutant P23H destabilizes rod photoreceptor disk membranes.
2012,
Pubmed
,
Xenbase
Hamm,
Controlled rod cell ablation in transgenic Xenopus laevis.
2009,
Pubmed
,
Xenbase
Illing,
A rhodopsin mutant linked to autosomal dominant retinitis pigmentosa is prone to aggregate and interacts with the ubiquitin proteasome system.
2002,
Pubmed
Kopito,
Aggresomes, inclusion bodies and protein aggregation.
2000,
Pubmed
Kosmaoglou,
Molecular chaperones and photoreceptor function.
2008,
Pubmed
Kroemer,
Autophagic cell death: the story of a misnomer.
2008,
Pubmed
Kruse,
Autophagy: an ER protein quality control process.
2006,
Pubmed
Kunchithapautham,
Autophagy is one of the multiple mechanisms active in photoreceptor degeneration.
2007,
Pubmed
Kunchithapautham,
Apoptosis and autophagy in photoreceptors exposed to oxidative stress.
2007,
Pubmed
Kunchithapautham,
Differential effects of rapamycin on rods and cones during light-induced stress in albino mice.
2011,
Pubmed
Lee,
Xenopus laevis tadpoles can regenerate neural retina lost after physical excision but cannot regenerate photoreceptors lost through targeted ablation.
2013,
Pubmed
,
Xenbase
Lee,
Dysmorphic photoreceptors in a P23H mutant rhodopsin model of retinitis pigmentosa are metabolically active and capable of regenerating to reverse retinal degeneration.
2012,
Pubmed
,
Xenbase
Levine,
Autophagy in the pathogenesis of disease.
2008,
Pubmed
Lin,
IRE1 signaling affects cell fate during the unfolded protein response.
2007,
Pubmed
Lin,
Misfolded proteins and retinal dystrophies.
2010,
Pubmed
Lobanova,
Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration.
2013,
Pubmed
Lohr,
Multiple, parallel cellular suicide mechanisms participate in photoreceptor cell death.
2006,
Pubmed
MacKenzie,
Localization of binding sites for carboxyl terminal specific anti-rhodopsin monoclonal antibodies using synthetic peptides.
1984,
Pubmed
Mann,
Molecular characterization of light chain 3. A microtubule binding subunit of MAP1A and MAP1B.
1994,
Pubmed
Mendes,
Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy.
2005,
Pubmed
Moritz,
A functional rhodopsin-green fluorescent protein fusion protein localizes correctly in transgenic Xenopus laevis retinal rods and is expressed in a time-dependent pattern.
2001,
Pubmed
,
Xenbase
Moritz,
Recent insights into the mechanisms underlying light-dependent retinal degeneration from X. laevis models of retinitis pigmentosa.
2010,
Pubmed
,
Xenbase
Nakazawa,
Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin.
2007,
Pubmed
Noorwez,
Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa.
2003,
Pubmed
Organisciak,
Retinal light damage: mechanisms and protection.
2010,
Pubmed
Peterson,
Arrestin migrates in photoreceptors in response to light: a study of arrestin localization using an arrestin-GFP fusion protein in transgenic frogs.
2003,
Pubmed
,
Xenbase
Ravikumar,
Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy.
2002,
Pubmed
Remé,
Modification of autophagic degradation by medium- and illumination conditions in frog visual cells in vitro.
1984,
Pubmed
Remé,
Autophagy in frog visual cells in vitro.
1980,
Pubmed
Remé,
Photoreceptor autophagy: effects of light history on number and opsin content of degradative vacuoles.
1999,
Pubmed
Rubinsztein,
In search of an "autophagomometer".
2009,
Pubmed
Sakami,
Probing mechanisms of photoreceptor degeneration in a new mouse model of the common form of autosomal dominant retinitis pigmentosa due to P23H opsin mutations.
2011,
Pubmed
Sarkar,
Autophagic clearance of aggregate-prone proteins associated with neurodegeneration.
2009,
Pubmed
Sohocki,
Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies.
2001,
Pubmed
Tam,
Characterization of rhodopsin P23H-induced retinal degeneration in a Xenopus laevis model of retinitis pigmentosa.
2006,
Pubmed
,
Xenbase
Tam,
The role of rhodopsin glycosylation in protein folding, trafficking, and light-sensitive retinal degeneration.
2009,
Pubmed
,
Xenbase
Tam,
Photoactivation-induced instability of rhodopsin mutants T4K and T17M in rod outer segments underlies retinal degeneration in X. laevis transgenic models of retinitis pigmentosa.
2014,
Pubmed
,
Xenbase
Tam,
The dependence of retinal degeneration caused by the rhodopsin P23H mutation on light exposure and vitamin a deprivation.
2010,
Pubmed
,
Xenbase
Tam,
Dark rearing rescues P23H rhodopsin-induced retinal degeneration in a transgenic Xenopus laevis model of retinitis pigmentosa: a chromophore-dependent mechanism characterized by production of N-terminally truncated mutant rhodopsin.
2007,
Pubmed
,
Xenbase
VENABLE,
A SIMPLIFIED LEAD CITRATE STAIN FOR USE IN ELECTRON MICROSCOPY.
1965,
Pubmed
Webb,
Alpha-Synuclein is degraded by both autophagy and the proteasome.
2003,
Pubmed
Winslow,
α-Synuclein impairs macroautophagy: implications for Parkinson's disease.
2010,
Pubmed
Yao,
The role of ubiquitin in autophagy-dependent protein aggregate processing.
2010,
Pubmed
