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Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age
PURPOSE: To investigate age-associated changes in retinal ganglion cell (RGC) response to elevated intraocular pressure (IOP), and to explore the mechanism underlying these changes. Specifically, the effect of aging on inhibitor of apoptosis (IAP) gene family expression was investigated in glaucomat...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Vision
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783363/ https://www.ncbi.nlm.nih.gov/pubmed/24146536 |
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author | Levkovitch-Verbin, Hani Vander, Shelly Makarovsky, Daria Lavinsky, Fabio |
author_facet | Levkovitch-Verbin, Hani Vander, Shelly Makarovsky, Daria Lavinsky, Fabio |
author_sort | Levkovitch-Verbin, Hani |
collection | PubMed |
description | PURPOSE: To investigate age-associated changes in retinal ganglion cell (RGC) response to elevated intraocular pressure (IOP), and to explore the mechanism underlying these changes. Specifically, the effect of aging on inhibitor of apoptosis (IAP) gene family expression was investigated in glaucomatous eyes. METHODS: IOP was induced unilaterally in 82 Wistar rats using the translimbal photocoagulation laser model. IOP was measured using a TonoLab tonometer. RGC survival was evaluated in 3-, 6-, 13-, and 18-month-old animals. Changes in the RNA profiles of young (3-month-old) and old glaucomatous retinas were examined by PCR array for apoptosis; changes in selected genes were validated by real-time PCR; and changes in selected proteins were localized by immunohistochemistry. RESULTS: There were no significant IOP differences between the age groups. However, there was a natural significant loss of RGCs with aging and this was more prevalent in glaucomatous eyes. The number of RGCs in glaucomatous eyes decreased from 669±123 RGC/mm(2) at 3 months to 486±114 RGC/mm(2) at 6 months and 189±46.5 RGC/mm(2) at 18 months (n=4–8, p=0.048, analysis of variance). The PCR array revealed different changes in proapoptotic and prosurvival genes between young and old eyes. The two important prosurvival genes, IAP-1 and X-linked IAP (XIAP), acted in opposite directions in 3-month-old and 15-month-old rats, and were significantly decreased in aged glaucomatous retinas, while their expression increased significantly in young glaucomatous eyes. P53 levels did not vary between young glaucomatous and normal fellow eyes, but were reduced with age. B-cell leukemia/lymphoma 2 (Bcl-2) family members and tumor necrosis factor (TNF)-α expression were unaffected by age. Immunohistochemistry results suggested that the sources of changes in IAP-1 protein expression are RGCs and glial cells, and that most XIAP secretion comes from RGCs. CONCLUSIONS: Decreased IAP-1 and XIAP gene expression in aged eyes may predispose RGCs to increased vulnerability to glaucomatous damage. These findings suggest that aging impairs the endogenous neuroprotective mechanism of RGCs evoked by elevated IOP. |
format | Online Article Text |
id | pubmed-3783363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Molecular Vision |
record_format | MEDLINE/PubMed |
spelling | pubmed-37833632013-10-21 Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age Levkovitch-Verbin, Hani Vander, Shelly Makarovsky, Daria Lavinsky, Fabio Mol Vis Research Article PURPOSE: To investigate age-associated changes in retinal ganglion cell (RGC) response to elevated intraocular pressure (IOP), and to explore the mechanism underlying these changes. Specifically, the effect of aging on inhibitor of apoptosis (IAP) gene family expression was investigated in glaucomatous eyes. METHODS: IOP was induced unilaterally in 82 Wistar rats using the translimbal photocoagulation laser model. IOP was measured using a TonoLab tonometer. RGC survival was evaluated in 3-, 6-, 13-, and 18-month-old animals. Changes in the RNA profiles of young (3-month-old) and old glaucomatous retinas were examined by PCR array for apoptosis; changes in selected genes were validated by real-time PCR; and changes in selected proteins were localized by immunohistochemistry. RESULTS: There were no significant IOP differences between the age groups. However, there was a natural significant loss of RGCs with aging and this was more prevalent in glaucomatous eyes. The number of RGCs in glaucomatous eyes decreased from 669±123 RGC/mm(2) at 3 months to 486±114 RGC/mm(2) at 6 months and 189±46.5 RGC/mm(2) at 18 months (n=4–8, p=0.048, analysis of variance). The PCR array revealed different changes in proapoptotic and prosurvival genes between young and old eyes. The two important prosurvival genes, IAP-1 and X-linked IAP (XIAP), acted in opposite directions in 3-month-old and 15-month-old rats, and were significantly decreased in aged glaucomatous retinas, while their expression increased significantly in young glaucomatous eyes. P53 levels did not vary between young glaucomatous and normal fellow eyes, but were reduced with age. B-cell leukemia/lymphoma 2 (Bcl-2) family members and tumor necrosis factor (TNF)-α expression were unaffected by age. Immunohistochemistry results suggested that the sources of changes in IAP-1 protein expression are RGCs and glial cells, and that most XIAP secretion comes from RGCs. CONCLUSIONS: Decreased IAP-1 and XIAP gene expression in aged eyes may predispose RGCs to increased vulnerability to glaucomatous damage. These findings suggest that aging impairs the endogenous neuroprotective mechanism of RGCs evoked by elevated IOP. Molecular Vision 2013-09-26 /pmc/articles/PMC3783363/ /pubmed/24146536 Text en Copyright © 2013 Molecular Vision. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Levkovitch-Verbin, Hani Vander, Shelly Makarovsky, Daria Lavinsky, Fabio Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age |
title | Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age |
title_full | Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age |
title_fullStr | Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age |
title_full_unstemmed | Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age |
title_short | Increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age |
title_sort | increase in retinal ganglion cells’ susceptibility to elevated intraocular pressure and impairment of their endogenous neuroprotective mechanism by age |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783363/ https://www.ncbi.nlm.nih.gov/pubmed/24146536 |
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