scholarly journals Impairments of Photoreceptor Outer Segments Renewal and Phototransduction Due to a Peripherin Rare Haplotype Variant: Insights from Molecular Modeling

2021 ◽  
Vol 22 (7) ◽  
pp. 3484
Author(s):  
Luigi Donato ◽  
Ebtesam Mohamed Abdalla ◽  
Concetta Scimone ◽  
Simona Alibrandi ◽  
Carmela Rinaldi ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Binding Sites ◽  
Outer Segment ◽  
Mutational Analysis ◽  
Childhood Onset ◽  
Rare Haplotype ◽  
Photoreceptor Outer Segment ◽  
Photoreceptor Outer Segments ◽  
Condition C ◽  
Related Pathway

Background: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents. Methods: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents. Afterwards, found variants were deeply, statistically, and in silico characterized to determine their possible effects and association with RPA. Results: Both brothers carry three missense PRPH2 variants in a homozygous condition (c.910C > A, c.929G > A, and c.1013A > C) and two promoter variants in RHO (c.-26A > G) and RLBP1 (c.-70G > A) genes, respectively. Haplotype analyses highlighted a PRPH2 rare haplotype variant (GAG), determining a possible alteration of PRPH2 binding with melanoregulin and other outer segment proteins, followed by photoreceptor outer segment instability. Furthermore, an altered balance of transcription factor binding sites, due to the presence of RHO and RLBP1 promoter variants, might determine a comprehensive downregulation of both genes, possibly altering the PRPH2 shared visual-related pathway. Conclusions: Despite several limitations, the study might be a relevant step towards detection of novel scenarios in RPA etiopathogenesis.

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

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.

PRCD is Concentrated at the Base of Photoreceptor Outer Segments and is Involved in Outer Segment Disc Formation

2019 ◽  
Author(s):  
Gilad Allon ◽  
Irit Mann ◽  
Lital Remez ◽  
Elisabeth Sehn ◽  
Leah Rizel ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Knockout Mice ◽  
Outer Segment ◽  
Mouse Retina ◽  
Cone Photoreceptors ◽  
Photoreceptor Outer Segment ◽  
Photoreceptor Outer Segments ◽  
Outer Segments ◽  
Rod And Cone Photoreceptors ◽  
Disc Formation

Abstract Mutations of the PRCD gene are associated with rod-cone degeneration in both dogs and humans. Prcd is expressed in the mouse eye as early as embryonic day 14. In the adult mouse retina PRCD is expressed in the outer segments of both rod and cone photoreceptors. Immunoelectron microscopy revealed that PRCD is located at the outer segment rim, and that it is highly concentrated at the base of the outer segment. Prcd-knockout mice present with progressive retinal degeneration, starting at 20 weeks of age and onwards. This process is reflected by a significant and progressive reduction of both scotopic and photopic electroretinographic responses, and by thinning of the retina, and specifically of the outer nuclear layer, indicating photoreceptor loss. Electron microscopy revealed severe damage to photoreceptor outer segments, which is associated with immigration of microglia cells to the Prcd-knockout retina, and accumulation of vesicles in the inter-photoreceptor space. Phagocytosis of photoreceptor outer segment discs by the retinal pigmented epithelium is severely reduced. Our data show that Prcd-knockout mice serve as a good model for retinal degeneration caused by PRCD mutations in humans. Our findings in these mice support the involvement of PRCD in outer segment disc formation of both rod and cone photoreceptors. Furthermore, they suggest a feedback mechanism which coordinates the rate of photoreceptor outer segment disc formation, shedding and phagocytosis. This study has important implications for understanding the function of PRCD in the retina, as well as for future development of treatment modalities for PRCD-deficiency in humans.

Early cone photoreceptor outer segment length shortening in RPGR X-linked retinitis pigmentosa

2020 ◽  
Author(s):  
Moreno Menghini ◽  
Jasleen K. Jolly ◽  
Anika Nanda ◽  
Laura Wood ◽  
Jasmina Cehajic-Kapetanovic ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Outer Segment ◽  
Segment Length ◽  
Cone Photoreceptor ◽  
Photoreceptor Outer Segment

scholarly journals Rab28 is localised to photoreceptor outer segments, regulates outer segment shedding but is not linked to retinal degeneration in zebrafish

2019 ◽  
Author(s):  
Stephen P. Carter ◽  
Ailís L. Moran ◽  
David Matallanas ◽  
Gavin J. McManus ◽  
Oliver E. Blacque ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Outer Segment ◽  
Membrane Surface ◽  
Photoreceptor Outer Segment ◽  
Membrane Surface Area ◽  
Photoreceptor Outer Segments ◽  
Outer Segments ◽  
Retinal Structure ◽  
Phototransduction Cascade ◽  
Shed Light

AbstractThe photoreceptor outer segment is the canonical example of a modified and highly specialised cilium, with an expanded membrane surface area in the form of discs or lamellae for efficient light detection. Many ciliary proteins are essential for normal photoreceptor function and cilium dysfunction often results in retinal degeneration leading to impaired vision. Herein, we investigate the function and localisation of the ciliary G-protein RAB28 in zebrafish cone photoreceptors. CRISPR-Cas9 generated rab28 mutant zebrafish display a reduction in shed outer segment material in the RPE at 1 month post fertilisation (mpf), but otherwise normal retinal structure and visual function up to 12 mpf. Cone photoreceptor-specific transgenic reporter lines show Rab28 localises almost exclusively to outer segments, independently of nucleotide binding. Co-immunoprecipitation analysis demonstrates tagged Rab28 interacts with components of the phototransduction cascade, including opsins, Phosphodiesterase 6C and Guanylate Cyclase 2D. Our data shed light on RAB28 function in cones and provide a model for RAB28-associated cone-rod dystrophy.

scholarly journals Distribution of guanylate cyclase within photoreceptor outer segments

1996 ◽  
Vol 109 (7) ◽  
pp. 1803-1812
Author(s):  
M.A. Hallett ◽  
J.L. Delaat ◽  
K. Arikawa ◽  
C.L. Schlamp ◽  
F. Kong ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Actin Filaments ◽  
Outer Segment ◽  
Essential Role ◽  
Photoreceptor Cells ◽  
Rod Photoreceptor ◽  
Light Activation ◽  
Photoreceptor Outer Segment ◽  
Photoreceptor Outer Segments ◽  
Vertebrate Photoreceptor

Guanylate cyclases play an essential role in the recovery of vertebrate photoreceptor cells after light activation. Here, we have investigated how one such guanylate cyclase, RetGC-1, is distributed within light- and dark-adapted rod photoreceptor cells. Guanylate cyclase activity partitioned with the photoreceptor outer segment (OS) cytoskeleton in a light-sensitive manner. RetGC-1 was found to bind actin filaments in actin blot overlays, suggesting a mechanism for its association with the OS cytoskeleton. In retinal sections, this enzyme was immunodetected only in the OSs, where it appeared to be distributed throughout the disk membranes.

scholarly journals Macular Pigment Optical Density and Photoreceptor Outer Segment Length as Predisease Biomarkers for Age-Related Macular Degeneration

2020 ◽  
Vol 9 (5) ◽  
pp. 1347 ◽  
Author(s):  
Norihiro Nagai ◽  
Sakiko Minami ◽  
Misa Suzuki ◽  
Hajime Shinoda ◽  
Toshihide Kurihara ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Optical Density ◽  
Outer Segment ◽  
Macular Pigment ◽  
Age Related Macular Degeneration ◽  
Segment Length ◽  
Macular Pigment Optical Density ◽  
Photoreceptor Outer Segment ◽  
Age Related ◽  
Fellow Eyes

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.

Reliability Assessment of a Rod Photoreceptor Outer Segment Grading System

2001 ◽  
Vol 72 (5) ◽  
pp. 573-579 ◽  
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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