Live Imaging of LysoTracker-Labelled Phagolysosomes Tracks Diurnal Phagocytosis of Photoreceptor Outer Segment Fragments in Rat RPE Tissue Ex Vivo

To explore predisease biomarkers, which may help screen for the risk of age-related macular degeneration (AMD) at very early stages, macular pigment optical density (MPOD) and photoreceptor outer segment (PROS) length were analyzed. Thirty late AMD fellow eyes, which are at high risk and represent the predisease condition of AMD, were evaluated and compared with 30 age-matched control eyes without retinal diseases; there was no early AMD involvement in the AMD fellow eyes. MPOD was measured using MPS2® (M.E. Technica Co. Ltd., Tokyo, Japan), and PROS length was measured based on optical coherence tomography images. MPOD levels and PROS length in the AMD fellow eyes were significantly lower and shorter, respectively, than in control eyes. MPOD and PROS length were positively correlated in control eyes (R = 0.386; p = 0.035) but not in AMD fellow eyes. Twenty (67%) AMD fellow eyes met the criteria of MPOD < 0.65 and/or PROS length < 35 μm, while only five (17%) control eyes did. After adjusting for age and sex, AMD fellow eyes more frequently satisfied the definition (p < 0.001; 95% confidence interval, 3.50–60.4; odds ratio, 14.6). The combination of MPOD and PROS length may be a useful biomarker for screening predisease AMD patients, although further studies are required in this regard.

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Mouse Fetal Whole Intestine Culture System for Ex Vivo Manipulation of Signaling Pathways and Three-dimensional Live Imaging of Villus Development

Journal of Visualized Experiments ◽

10.3791/51817 ◽

2014 ◽

Cited By ~ 3

Author(s):

Katherine D. Walton ◽

Åsa Kolterud

Keyword(s):

Signaling Pathways ◽

Culture System ◽

Ex Vivo ◽

Three Dimensional ◽

Live Imaging

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Reliability Assessment of a Rod Photoreceptor Outer Segment Grading System

Experimental Eye Research ◽

10.1006/exer.2001.0987 ◽

2001 ◽

Vol 72 (5) ◽

pp. 573-579 ◽

Cited By ~ 4

Author(s):

Monica M Jablonski ◽

Marshall J Graney ◽

Stephen B Kritchevsky ◽

Alessandro Iannaccone

Keyword(s):

Outer Segment ◽

Reliability Assessment ◽

Grading System ◽

Rod Photoreceptor ◽

Photoreceptor Outer Segment

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Correlation between brain volume and retinal photoreceptor outer segment volume in normal aging and neurodegenerative diseases

PLoS ONE ◽

10.1371/journal.pone.0237078 ◽

2020 ◽

Vol 15 (9) ◽

pp. e0237078

Author(s):

Atsuro Uchida ◽

Jagan A. Pillai ◽

Robert Bermel ◽

Stephen E. Jones ◽

Hubert Fernandez ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Outer Segment ◽

Brain Volume ◽

Normal Aging ◽

Photoreceptor Outer Segment ◽

Retinal Photoreceptor ◽

Segment Volume

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TULP1 and TUB Are Required for Specific Localization of PRCD to Photoreceptor Outer Segments

International Journal of Molecular Sciences ◽

10.3390/ijms21228677 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8677

Author(s):

Lital Remez ◽

Ben Cohen ◽

Mariela J. Nevet ◽

Leah Rizel ◽

Tamar Ben-Yosef

Keyword(s):

Protein Interactions ◽

Mammalian Cells ◽

Outer Segment ◽

Protein Protein Interactions ◽

Photoreceptor Outer Segment ◽

Photoreceptor Outer Segments ◽

Outer Segments ◽

Yeast Two Hybrid System ◽

Specific Localization ◽

Recruitment System

Photoreceptor disc component (PRCD) is a small protein which is exclusively localized to photoreceptor outer segments, and is involved in the formation of photoreceptor outer segment discs. Mutations in PRCD are associated with retinal degeneration in humans, mice, and dogs. The purpose of this work was to identify PRCD-binding proteins in the retina. PRCD protein-protein interactions were identified when implementing the Ras recruitment system (RRS), a cytoplasmic-based yeast two-hybrid system, on a bovine retina cDNA library. An interaction between PRCD and tubby-like protein 1 (TULP1) was identified. Co-immunoprecipitation in transfected mammalian cells confirmed that PRCD interacts with TULP1, as well as with its homolog, TUB. These interactions were mediated by TULP1 and TUB highly conserved C-terminal tubby domain. PRCD localization was altered in the retinas of TULP1- and TUB-deficient mice. These results show that TULP1 and TUB, which are involved in the vesicular trafficking of several photoreceptor proteins from the inner segment to the outer segment, are also required for PRCD exclusive localization to photoreceptor outer segment discs.

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Photosensitized Oxidative Stress to ARPE-19 Cells Decreases Protein Receptors that Mediate Photoreceptor Outer Segment Phagocytosis

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.12-11154 ◽

2013 ◽

Vol 54 (3) ◽

pp. 2276 ◽

Cited By ~ 13

Author(s):

Magdalena M. Olchawa ◽

Anja M. Herrnreiter ◽

Christine M. B. Skumatz ◽

Mariusz Zareba ◽

Tadeusz J. Sarna ◽

...

Keyword(s):

Oxidative Stress ◽

Outer Segment ◽

Photoreceptor Outer Segment ◽

Protein Receptors

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Loss of CEP162 function at the primary cilium delays ciliogenesis and causes retinal ciliopathy in humans

10.1101/2021.11.23.469779 ◽

2021 ◽

Author(s):

Nafisa Nuzhat ◽

Kristof Van Schil ◽

Sandra Liakopoulos ◽

Miriam Bauwens ◽

Alfredo Dueñas Rey ◽

...

Keyword(s):

Transition Zone ◽

Primary Cilium ◽

Outer Segment ◽

Retinal Dystrophy ◽

Mrna Levels ◽

Loss Of Function ◽

Photoreceptor Outer Segment ◽

Zone Formation ◽

Mother Centriole

Ciliopathies often comprise retinal degeneration since the photoreceptor outer segment is an adapted primary cilium. CEP162 is a distal end centriolar protein required for proper transition zone assembly during ciliogenesis and whose loss causes ciliopathy in zebrafish. CEP162 has so far not been implicated in human disease. Here, we identified a homozygous CEP162 frameshift variant, c.1935dupA (p.(E646R*5)), in retinitis pigmentosa patients from two unrelated Moroccan families, likely representing a founder allele. We found that even though mRNA levels were reduced, the truncated CEP162-E646R*5 protein was expressed and localized to the mitotic spindle during mitosis, but not at the basal body of the cilium. In CEP162 knockdown cells, expression of the truncated CEP162-E646R*5 protein is unable to restore ciliation indicating its loss of function at the cilium. In patient fibroblasts, cilia overcome the absence of CEP162 from the primary cilium by delaying ciliogenesis through the persistence of CP110 at the mother centriole. The patient fibroblasts are ultimately able to extend some abnormally long cilia that are missing key transition zone components. Defective transition zone formation likely disproportionately affects the long-living ciliary outer segment of photoreceptors resulting in retinal dystrophy. CEP162 is expressed in human retina, and we show that wild-type CEP162, but not truncated CEP162-E646R*5, specifically localizes to the distal end of centrioles of mouse photoreceptor cilia. Together, our genetic, cell-based, and in vivo modeling establish that CEP162 deficiency causes retinal ciliopathy in humans.

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Cell shape anisotropy and motility constrain self-organised feather pattern fidelity in birds

10.1101/2021.01.22.427778 ◽

2021 ◽

Author(s):

Camille Curantz ◽

Richard Bailleul ◽

Magdalena Hidalgo ◽

Melina Durande ◽

François Graner ◽

...

Keyword(s):

Cell Motility ◽

Cell Shape ◽

Species Differences ◽

Ex Vivo ◽

Live Imaging ◽

Developmental Pattern ◽

Stochastic Fluctuations ◽

Dermal Cell ◽

Self Organisation ◽

Cell Anisotropy

SummaryCellular self-organisation can emerge from stochastic fluctuations in properties of a developing tissue1–3. This mechanism explains the production of various motifs seen in nature4–7. However, events channelling its outcomes such that patterns are produced with reproducible precision key to fitness remain unexplored. Here, we compared the dynamic emergence of feather primordia arrays in poultry, finch, emu, ostrich and penguin embryos and correlated inter-species differences in pattern fidelity to the amplitude of dermal cell anisotropy in the un-patterned tissue. Using live imaging and ex vivo perturbations in these species, we showed that cell anisotropy optimises cell motility for sharp and precisely located primordia formation, and thus, proper pattern geometry. These results evidence a mechanism through which collective cellular properties of a developmental pattern system ensure stability in its self-organisation and contribute to its evolution.

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