MiRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE58501 | GEO | 2014/06/20
SECONDARY ACCESSION(S): PRJNA253145
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-20 | E-GEOD-58501 | biostudies-arrayexpress
Project description:MiRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function
| PRJNA253145 | ENA
Project description:Lecithin retinol acyl transferase (LRAT) and retinal pigment epithelium protein 65 (RPE65) are key enzymes of the retinoid cycle. In Lrat(-/-) and Rpe65(-/-) mice, models of human Leber congenital amaurosis, the retinoid cycle is disrupted and 11-cis-retinal, the chromophore of visual pigments, is not produced. The Lrat(-/-) and Rpe65(-/-) retina phenotype presents with rapid sectorial cone degeneration, and the visual pigments, S-opsin and M/L-opsin, fail to traffic to cone outer segments appropriately. In contrast, rod opsin traffics normally in mutant rods. Concomitantly, guanylate cyclase 1, cone T alpha-subunit, cone phosphodiesterase 6alpha' (PDE6alpha'), and GRK1 (G-protein-coupled receptor kinase 1; opsin kinase) are not transported to Lrat(-/-) and Rpe65(-/-) cone outer segments. Aberrant localization of these membrane-associated proteins was evident at postnatal day 15, before the onset of ventral and central cone degeneration. Protein levels of cone T alpha and cone PDE6alpha' were reduced, whereas their transcript levels were unchanged, suggesting posttranslational degradation. In an Rpe65(-/-)Rho(-/-) double knock-out model, trafficking of cone pigments and membrane-associated cone phototransduction polypeptides to the outer segments proceeded normally after 11-cis-retinal administration. These results suggest that ventral and central cone opsins must be regenerated with 11-cis-retinal to permit transport to the outer segments. Furthermore, the presence of 11-cis-retinal is essential for proper transport of several membrane-associated cone phototransduction polypeptides in these cones.
| S-EPMC2562706 | biostudies-literature
Project description:When radiolabeled precursors and autoradiography are used to investigate turnover of protein components in photoreceptive cone outer segments (COSs), the labeled components--primarily visual pigment molecules (opsins)--are diffusely distributed along the COS. To further assess this COS labeling pattern, we derive a simplified mass-transfer model for quantifying the contributions of advective and diffusive mechanisms to the distribution of opsins within COSs of the frog retina. Two opsin-containing regions of the COS are evaluated: the core axial array of disks and the plasmalemma. Numerical solutions of the mass-transfer model indicate three distinct stages of system evolution. In the first stage, plasmalemma diffusion is dominant. In the second stage, the plasmalemma density reaches a metastable state and transfer between the plasmalemma and disk region occurs, which is followed by an increase in density that is qualitatively similar for both regions. The final stage consists of both regions slowly evolving to the steady-state solution. Our results indicate that autoradiographic and cognate approaches for tracking labeled opsins in the COS cannot be effective methodologies for assessing new disk formation at the base of the COS.
| S-EPMC3030251 | biostudies-literature
Project description:Photoreceptors are damaged in many common eye diseases, such as macular degeneration, retinal detachment, and retinitis pigmentosa. The development of methods to promote the repair or replacement of affected photoreceptors is a major goal of vision research. In this context, it would be useful to know whether photoreceptors are capable of undergoing some degree of spontaneous regeneration after injury. We report a subject who lost retinal function in a wide zone around the optic disc, giving rise to massive enlargement of the physiological blind spot. Imaging with an adaptive optics scanning laser ophthalmoscope (AOSLO) showed depletion of cone outer segments in the affected retina. A year later visual function had improved, with shrinkage of the enlarged blind spot. AOSLO imaging showed repopulation of cone outer segments, although their density remained below normal. There was a one-to-one match between sites of formerly missing outer segments and new outer segments that had appeared over the course of the year's recovery. This correspondence provided direct morphological evidence that damaged cones are capable, under some circumstances, of generating new outer segments.
| S-EPMC4515765 | biostudies-literature
Project description:Photoreceptor outer segments (OSs) are essential for our visual perception, and take either rod or cone forms. The cell biological basis for the formation of rods is well established; however, the mechanism of cone formation is ill characterized. While Xenopus rods are called rods, they exhibit cone-shaped OSs during the early process of development. To visualize the dynamic reorganization of disk membranes, opsin and peripherin/rds were fused to a fluorescent protein, Dendra2, and expressed in early developing rod photoreceptors, in which OSs are still cone-shaped. Dendra2 is a fluorescent protein which can be converted from green to red irreversibly, and thus allows spatiotemporal labeling of proteins. Using a photoconversion technique, we found that disk membranes are assembled at the base of cone-shaped OSs. After incorporation into disks, however, Opsin-Dendra2 was also trafficked from old to new disk membranes, consistent with the hypothesis that retrograde trafficking of membrane components contributes to the larger disk membrane observed toward the base of the cone-shaped OS. Such retrograde trafficking is cargo-specific and was not observed for peripherin/rds-Dendra2. The trafficking is unlikely mediated by diffusion, since the disk membranes have a closed configuration, as evidenced by CNGA1 labeling of the plasma membrane. Consistent with retrograde trafficking, the axoneme, which potentially mediates retrograde intraflagellar trafficking, runs through the entire axis of OSs. This study provides an insight into the role of membrane reorganization in developing photoreceptor OSs, and proves that retrograde trafficking of membrane cargoes can occur there.
| S-EPMC4142104 | biostudies-literature
Project description:Best disease is a macular dystrophy caused by mutations in the BEST1 gene. Affected individuals exhibit a reduced electro-oculographic (EOG) response to changes in light exposure and have significantly longer outer segments (OS) than age-matched controls. The purpose of this study was to investigate the anatomical changes in the outer retina during dark and light adaptation in unaffected and Best disease subjects, and to compare these changes to the EOG.Unaffected (n = 11) and Best disease patients (n = 7) were imaged at approximately 4-minute intervals during an approximately 40-minute dark-light cycle using spectral domain optical coherence tomography (SD-OCT). EOGs of two subjects were obtained under the same conditions. Automated three-dimensional (3-D) segmentation allowed measurement of light-related changes in the distances between five retinal surfaces.In normal subjects, there was a significant decrease in outer segment equivalent length (OSEL) of -2.14 ?m (95% confidence interval [CI], -1.77 to -2.51 ?m) 10 to 20 minutes after the start of light adaptation, while Best disease subjects exhibited a significant increase in OSEL of 2.07 ?m (95% CI, 1.79-2.36 ?m). The time course of the change in OS length corresponded to that of the EOG waveform.Our results strongly suggest that the light peak phase of the EOG is temporally related to a decreased OSEL in normal subjects, and the lack of a light peak phase in Best disease subjects is associated with an increase in OSEL. One potential role of Bestrophin-1 is to trigger an increase in the standing potential that approximates the OS to the apical surface of the RPE to facilitate phagocytosis.
| S-EPMC3668803 | biostudies-literature
Project description:Signal transduction in outer segments of vertebrate photoreceptors is mediated by a series of reactions among multiple polypeptides that form protein-protein complexes within or on the surface of the disk and plasma membranes. The individual components in the activation reactions include the photon receptor rhodopsin and the products of its absorption of light, the three subunits of the G protein, transducin, the four subunits of the cGMP phosphodiesterase, PDE6 and the four subunits of the cGMP-gated cation channel. Recovery involves membrane complexes with additional polypeptides including the Na(+)/Ca(2+), K(+) exchanger, NCKX2, rhodopsin kinases RK1 and RK7, arrestin, guanylate cyclases, guanylate cyclase activating proteins, GCAP1 and GCAP2, and the GTPase accelerating complex of RGS9-1, G(beta5L), and membrane anchor R9AP. Modes of membrane binding by these polypeptides include transmembrane helices, fatty acyl or isoprenyl modifications, polar interactions with lipid head groups, non-polar interactions of hydrophobic side chains with lipid hydrocarbon phase, and both polar and non-polar protein-protein interactions. In the course of signal transduction, complexes among these polypeptides form and dissociate, and undergo structural rearrangements that are coupled to their interactions with and catalysis of reactions by small molecules and ions, including guanine nucleotides, ATP, Ca(2+), Mg(2+), and lipids. The substantial progress that has been made in understanding the composition and function of these complexes is reviewed, along with the more preliminary state of our understanding of the structures of these complexes and the challenges and opportunities that present themselves for deepening our understanding of these complexes, and how they work together to convert a light signal into an electrical signal.
| S-EPMC2615670 | biostudies-literature
Project description:PurposeThis study was designed to verify light-induced outer segment (OS) length shrinkage of rod photoreceptors and to characterize its anatomic source at disc-level resolution.MethodsFrog (Rana pipiens) retinas were used for this study. Time-lapse light microscopy of freshly isolated OSs was employed to test transient rod OS changes at 10 ms temporal resolution. Histological light microscopy of dark- and light-adapted retinas was used to confirm light-induced rod OS length changes; and transmission electron microscopy (TEM) was used to quantify light-driven structural perturbation of rod OSs at disc level resolution.ResultsTime-lapse light microscopy images verified transient length shrinking responses in freshly isolated rod OSs. Histological light microscopy images confirmed reduced rod OS lengths in light-adapted retinas, compared to that of dark-adapted retinas. TEM images disclosed shortened inter-disc distances in light-adapted retinas compared to dark-adapted retinas.ConclusionsLight-induced rod OS length shrinkage was confirmed using time-lapse light microscopy of isolated rod OSs and histological light microscopy of dark- and light-adapted retinas. TEM revealed that the rod OS length shrinkage was correlated to the light-driven decrease of the space between individual discs, not the disc thickness itself.Translational relevanceLight-induced transient rod response promises a noninvasive biomarker for early diagnosis of age-related macular degeneration and retinitis pigmentosa, in which the rod photoreceptors are known to be more vulnerable than cone photoreceptors.
| S-EPMC6314056 | biostudies-literature
Project description:PurposeThis study aimed to establish a novel choroidal neovascularization (CNV) mouse model through subretinally injecting malondialdehyde (MDA)-modified photoreceptor outer segments (POS), which was more consistent with the pathogenesis of wet age-related macular degeneration (AMD).MethodsMDA-modified POS were subretinally injected in C57BL/6J mice. Four weeks later, to assess the volume of CNV and the morphology of retinal pigment epithelium (RPE), isolectin B4 and zonula occludens-1 antibody were used for immunostaining. Fundus fluorescent angiography and optical coherence tomography imaging were used to describe the morphologic features of CNV. Transepithelial resistance was measured on polarized ARPE-19 cells. Vascular endothelial growth factor levels in the cell culture medium were detected by enzyme-linked immunosorbent assay. The protein and messenger RNA expression levels of autophagy markers were measured using Western blot and quantitative polymerase chain reaction.ResultsCNV and RPE atrophy were successfully induced in the mouse model. MDA-modified POS also significantly increased the expression of vascular endothelial growth factor and disrupted cell junctions in RPE cells. In addition, MDA-modified POS induced autophagy-lysosomal impairment in RPE cells.ConclusionsSubretinal injection of MDA-modified POS may generate a feasible CNV model that simulates the AMD pathological process.Translational relevanceThis study expands the understanding of the role of MDA in AMD pathogenesis, which provides a potential therapeutic target of AMD.
| S-EPMC8762676 | biostudies-literature