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Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction
PURPOSE: To define remodeling of photoreceptor synaptic terminals and second-order retinal neurons in canine X-linked progressive retinal atrophy 1 caused by a five-nucleotide deletion in the RPGR exon ORF15. METHODS: Retinas of normal and mutant dogs were used for gene expression, Western blot, and...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405958/ https://www.ncbi.nlm.nih.gov/pubmed/32176262 http://dx.doi.org/10.1167/iovs.61.3.11 |
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author | Appelbaum, Tatyana Santana, Evelyn Aguirre, Gustavo D. |
author_facet | Appelbaum, Tatyana Santana, Evelyn Aguirre, Gustavo D. |
author_sort | Appelbaum, Tatyana |
collection | PubMed |
description | PURPOSE: To define remodeling of photoreceptor synaptic terminals and second-order retinal neurons in canine X-linked progressive retinal atrophy 1 caused by a five-nucleotide deletion in the RPGR exon ORF15. METHODS: Retinas of normal and mutant dogs were used for gene expression, Western blot, and immunohistochemistry. Cell-specific markers were used to examine disease-dependent retinal remodeling. RESULTS: In mutant retinas, a number of rod axon terminals retract into the outer nuclear layer. This neuritic atrophy preceded significant loss of rods and was evident early in disease. Rod bipolar and horizontal cell processes were found to extend into the outer nuclear layer, where they seemed to form contacts with the spherules of rod photoreceptors. No ectopic rewiring was observed. Because cytoskeletal reorganization was previously shown to underlie photoreceptor axon retraction, we examined normal and mutant retinas for expression of axon guidance receptors ROBO1 and ROBO2, which are known to regulate actin cytoskeleton dynamics. We found that the overall expression of both ROBO1 and ROBO2 is retained at the same level in premature and fully developed normal retinas. However, analysis of predisease and early disease retinas identified markedly decreased levels of ROBO1 in rod spherules compared with controls. In contrast, no differences in ROBO1 signals were noted in cone pedicles in normal and mutant retinas, where ROBO1 levels remained similarly low. CONCLUSIONS: Depletion of ROBO1 in rod synaptic terminals correlates with the remodeling of axonal and dendritic processes in the outer retina of dogs with X-linked progressive retinal atrophy 1 and may play a role in the retraction of rod axons. |
format | Online Article Text |
id | pubmed-7405958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-74059582020-08-19 Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction Appelbaum, Tatyana Santana, Evelyn Aguirre, Gustavo D. Invest Ophthalmol Vis Sci Retinal Cell Biology PURPOSE: To define remodeling of photoreceptor synaptic terminals and second-order retinal neurons in canine X-linked progressive retinal atrophy 1 caused by a five-nucleotide deletion in the RPGR exon ORF15. METHODS: Retinas of normal and mutant dogs were used for gene expression, Western blot, and immunohistochemistry. Cell-specific markers were used to examine disease-dependent retinal remodeling. RESULTS: In mutant retinas, a number of rod axon terminals retract into the outer nuclear layer. This neuritic atrophy preceded significant loss of rods and was evident early in disease. Rod bipolar and horizontal cell processes were found to extend into the outer nuclear layer, where they seemed to form contacts with the spherules of rod photoreceptors. No ectopic rewiring was observed. Because cytoskeletal reorganization was previously shown to underlie photoreceptor axon retraction, we examined normal and mutant retinas for expression of axon guidance receptors ROBO1 and ROBO2, which are known to regulate actin cytoskeleton dynamics. We found that the overall expression of both ROBO1 and ROBO2 is retained at the same level in premature and fully developed normal retinas. However, analysis of predisease and early disease retinas identified markedly decreased levels of ROBO1 in rod spherules compared with controls. In contrast, no differences in ROBO1 signals were noted in cone pedicles in normal and mutant retinas, where ROBO1 levels remained similarly low. CONCLUSIONS: Depletion of ROBO1 in rod synaptic terminals correlates with the remodeling of axonal and dendritic processes in the outer retina of dogs with X-linked progressive retinal atrophy 1 and may play a role in the retraction of rod axons. The Association for Research in Vision and Ophthalmology 2020-03-16 /pmc/articles/PMC7405958/ /pubmed/32176262 http://dx.doi.org/10.1167/iovs.61.3.11 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Retinal Cell Biology Appelbaum, Tatyana Santana, Evelyn Aguirre, Gustavo D. Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction |
title | Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction |
title_full | Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction |
title_fullStr | Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction |
title_full_unstemmed | Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction |
title_short | Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction |
title_sort | critical decrease in the level of axon guidance receptor robo1 in rod synaptic terminals is followed by axon retraction |
topic | Retinal Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405958/ https://www.ncbi.nlm.nih.gov/pubmed/32176262 http://dx.doi.org/10.1167/iovs.61.3.11 |
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