title: Time course of retinal degeneration associated with the absence of 1, 4, 5-inositol trisphosphate receptor in Drosophila melanogaster.
abstract: The absence of the inositol trisphosphate receptor is associated with a gradual retinal degeneration in Drosophila melanogaster. To characterize the time-course profile of this process, mosaic flies expressing a null allele of the itp gene in the eye were studied by electroretinograms and electronic microscopy. Membrane contour alterations, disrupted mitochondria, altered morphology and even loss of photoreceptors were increased progressively starting 5 d after hatching, were more evident during days 10-15 and promoted highly disorganized structures thereafter. Comparison between electroretinograms recorded in wild type and mutant tissues showed progressive differences in the on and off transients as well as in the magnitude of the summed receptor potentials of photoreceptor cells from day 5 of hatching, [corrected] and the functional defects became progressively more severe. Unexpectedly, these alterations were detected not only in the non-pigmented mutant ommatidia, but also in the pigmented ommatidia, including heterozygous and twin clones expressing 1, 4, 5-inositol trisphosphate receptor (IP(3)R). To explore the mechanism underlying this degenerative process, the progression of pro-oxidant and apoptotic reactions was characterized by immunohistochemical techniques. Mutant ommatidia showed intermittent episodes of increased pro-oxidant reactions (detected as adducts of 4-hydroxy-nonenal) throughout the fly's life. Similarly, several episodes of active caspase 3, an apoptotic effector, were evident with the same time pattern. Episodes of enhanced lipid peroxidation and apoptosis were also observed in the pigmented ommatidia of the mosaic eyes. The results indicate that photoreceptors lacking IP(3)R suffer episodes of increased lipid peroxidation, which eventually perturb the retinal subcellular organization and disrupt the phototransduction process and cell viability. Pigmented ommatidia also showed a similar pattern of damage, indicating that the degenerative process is non-autonomous and is so intense that it propagated to the non-mutant retinal cells in the mosaic eyes. In conclusion, ommatidia with a null mutation of IP(3)R degenerate by a process associated with intermittent lipid peroxidation and apoptotic activities.
authors.affiliation: Instituto de Neurobiología, Querétaro, México.
authors.forename: Olivia
authors.initials: O
authors.lastname: Vázquez-Martínez
authors.forename: Angélica
authors.initials: A
authors.lastname: Loranca
authors.forename: Lourdes
authors.initials: L
authors.lastname: Palma-Tirado
authors.forename: Sabina
authors.initials: S
authors.lastname: Wischin-Fuentes
authors.forename: Mónica
authors.initials: M
authors.lastname: Villalobos-Leal
authors.forename: Anaid
authors.initials: A
authors.lastname: Antaramián
authors.forename: Juan
authors.initials: J
authors.lastname: Riesgo-Escovar
authors.forename: Rolando
authors.initials: R
authors.lastname: Hernández-Muñoz
authors.forename: Mauricio
authors.initials: M
authors.lastname: Díaz-Muñoz
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D004331:Drosophila melanogaster; D004596:Electroretinography / Q000379:methods; D005786:Gene Expression Regulation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism / Q000502:physiology*; D015227:Lipid Peroxidation; D009154:Mutation; D016877:Oxidants; D018384:Oxidative Stress; D010786:Photoreceptor Cells / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D016877:Oxidants; D002118:Calcium