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The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis
PURPOSE: Mutations in TCP-1 ring complex (TRiC) have been associated with Leber Congenital Amaurosis (LCA). TRiC is involved in protein folding and has 8 essential subunits including CCT5. Herein, we studied the retina of TRiC mutant zebrafish to evaluate the possible role of impaired actin and tubu...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PUBLISHED BY KNOWLEDGE E
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020782/ https://www.ncbi.nlm.nih.gov/pubmed/36937198 http://dx.doi.org/10.18502/jovr.v18i1.12726 |
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author | Berger, Silke D. Currie, Peter Berger, Joachim |
author_facet | Berger, Silke D. Currie, Peter Berger, Joachim |
author_sort | Berger, Silke |
collection | PubMed |
description | PURPOSE: Mutations in TCP-1 ring complex (TRiC) have been associated with Leber Congenital Amaurosis (LCA). TRiC is involved in protein folding and has 8 essential subunits including CCT5. Herein, we studied the retina of TRiC mutant zebrafish to evaluate the possible role of impaired actin and tubulin folding in LCA. METHODS: The cct5 [Formula: see text] retina was histologically studied using Toluidine Blue staining as well as TUNEL, BrdU-labeling, and Phalloidin assays. Retinal organisation was assessed by quantification of the cellularity utilising DAPI. RESULTS: Laminar organization of cct5 [Formula: see text] retinas was intact. Enhanced apoptosis throughout the cct5 [Formula: see text] retina was not compensated by higher proliferation rates, leaving the cct5 [Formula: see text] retina smaller in size. Quantification of retinal layer cellularity demonstrated that specifically the numbers of the amacrine and the retinal ganglion cells were depleted, suggesting that the cct5 [Formula: see text] retina was not uniformly affected by the reduced actin folding. CONCLUSION: Whereas the current literature suggests that LCA is predominantly affecting retinal photoreceptor cells and the retinal pigment epithelium, cct5 [Formula: see text] analyses demonstrated the important role of folding of actin by TRiC, suggesting that cct5 [Formula: see text] is a useful tool to specifically analyze the role of F-actin filaments in the context of LCA. |
format | Online Article Text |
id | pubmed-10020782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | PUBLISHED BY KNOWLEDGE E |
record_format | MEDLINE/PubMed |
spelling | pubmed-100207822023-03-18 The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis Berger, Silke D. Currie, Peter Berger, Joachim J Ophthalmic Vis Res Original Article PURPOSE: Mutations in TCP-1 ring complex (TRiC) have been associated with Leber Congenital Amaurosis (LCA). TRiC is involved in protein folding and has 8 essential subunits including CCT5. Herein, we studied the retina of TRiC mutant zebrafish to evaluate the possible role of impaired actin and tubulin folding in LCA. METHODS: The cct5 [Formula: see text] retina was histologically studied using Toluidine Blue staining as well as TUNEL, BrdU-labeling, and Phalloidin assays. Retinal organisation was assessed by quantification of the cellularity utilising DAPI. RESULTS: Laminar organization of cct5 [Formula: see text] retinas was intact. Enhanced apoptosis throughout the cct5 [Formula: see text] retina was not compensated by higher proliferation rates, leaving the cct5 [Formula: see text] retina smaller in size. Quantification of retinal layer cellularity demonstrated that specifically the numbers of the amacrine and the retinal ganglion cells were depleted, suggesting that the cct5 [Formula: see text] retina was not uniformly affected by the reduced actin folding. CONCLUSION: Whereas the current literature suggests that LCA is predominantly affecting retinal photoreceptor cells and the retinal pigment epithelium, cct5 [Formula: see text] analyses demonstrated the important role of folding of actin by TRiC, suggesting that cct5 [Formula: see text] is a useful tool to specifically analyze the role of F-actin filaments in the context of LCA. PUBLISHED BY KNOWLEDGE E 2023-02-21 /pmc/articles/PMC10020782/ /pubmed/36937198 http://dx.doi.org/10.18502/jovr.v18i1.12726 Text en Copyright © 2023 Berger et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Berger, Silke D. Currie, Peter Berger, Joachim The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis |
title | The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis |
title_full | The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis |
title_fullStr | The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis |
title_full_unstemmed | The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis |
title_short | The Role of TRiC-enhanced Actin Folding in Leber Congenital Amaurosis |
title_sort | role of tric-enhanced actin folding in leber congenital amaurosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020782/ https://www.ncbi.nlm.nih.gov/pubmed/36937198 http://dx.doi.org/10.18502/jovr.v18i1.12726 |
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