Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration

Amyloid-beta (Aβ)-related alterations, similar to those found in the brains of patients with Alzheimer's disease, have been observed in the retina of patients with glaucoma. Decreased levels of brain-derived neurotrophic factor (BDNF) are believed to be associated with the neurotoxic effects of...

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Main Authors: Mohd. Lazaldin, Mohd. Aizuddin, Iezhitsa, Igor, Agarwal, Renu, Agarwal, Puneet, Mohd. Ismail, Nafeeza
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2023
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Online Access:http://eprints.utm.my/106032/1/MohdAizuddinMohd2023_NeuroprotectiveEffectsofExogenousBrainDerived.pdf
http://eprints.utm.my/106032/
http://dx.doi.org/10.4103/1673-5374.346546
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Institution: Universiti Teknologi Malaysia
Language: English
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spelling my.utm.1060322024-05-29T06:40:40Z http://eprints.utm.my/106032/ Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration Mohd. Lazaldin, Mohd. Aizuddin Iezhitsa, Igor Agarwal, Renu Agarwal, Puneet Mohd. Ismail, Nafeeza Q Science (General) Amyloid-beta (Aβ)-related alterations, similar to those found in the brains of patients with Alzheimer's disease, have been observed in the retina of patients with glaucoma. Decreased levels of brain-derived neurotrophic factor (BDNF) are believed to be associated with the neurotoxic effects of Aβ peptide. To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ 1-40-induced retinal injury in Sprague-Dawley rats, we treated rats by intravitreal administration of phosphate-buffered saline (control), Aβ 1-40 (5 nM), or Aβ 1-40 (5 nM) combined with BDNF (1 μg/mL). We found that intravitreal administration of Aβ 1-40 induced retinal ganglion cell apoptosis. Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ 1-40 group than in the control and BDNF groups. In the Aβ 1-40 group, low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression. BDNF abolished Aβ 1-40-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression. These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ 1-40 by activating the BDNF-TrkB signaling pathway in rats. Wolters Kluwer Medknow Publications 2023-02 Article PeerReviewed application/pdf en http://eprints.utm.my/106032/1/MohdAizuddinMohd2023_NeuroprotectiveEffectsofExogenousBrainDerived.pdf Mohd. Lazaldin, Mohd. Aizuddin and Iezhitsa, Igor and Agarwal, Renu and Agarwal, Puneet and Mohd. Ismail, Nafeeza (2023) Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration. Neural Regeneration Research, 18 (2). pp. 382-388. ISSN 1673-5374 http://dx.doi.org/10.4103/1673-5374.346546 DOI:10.4103/1673-5374.346546
institution Universiti Teknologi Malaysia
building UTM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Teknologi Malaysia
content_source UTM Institutional Repository
url_provider http://eprints.utm.my/
language English
topic Q Science (General)
spellingShingle Q Science (General)
Mohd. Lazaldin, Mohd. Aizuddin
Iezhitsa, Igor
Agarwal, Renu
Agarwal, Puneet
Mohd. Ismail, Nafeeza
Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration
description Amyloid-beta (Aβ)-related alterations, similar to those found in the brains of patients with Alzheimer's disease, have been observed in the retina of patients with glaucoma. Decreased levels of brain-derived neurotrophic factor (BDNF) are believed to be associated with the neurotoxic effects of Aβ peptide. To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ 1-40-induced retinal injury in Sprague-Dawley rats, we treated rats by intravitreal administration of phosphate-buffered saline (control), Aβ 1-40 (5 nM), or Aβ 1-40 (5 nM) combined with BDNF (1 μg/mL). We found that intravitreal administration of Aβ 1-40 induced retinal ganglion cell apoptosis. Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ 1-40 group than in the control and BDNF groups. In the Aβ 1-40 group, low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression. BDNF abolished Aβ 1-40-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression. These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ 1-40 by activating the BDNF-TrkB signaling pathway in rats.
format Article
author Mohd. Lazaldin, Mohd. Aizuddin
Iezhitsa, Igor
Agarwal, Renu
Agarwal, Puneet
Mohd. Ismail, Nafeeza
author_facet Mohd. Lazaldin, Mohd. Aizuddin
Iezhitsa, Igor
Agarwal, Renu
Agarwal, Puneet
Mohd. Ismail, Nafeeza
author_sort Mohd. Lazaldin, Mohd. Aizuddin
title Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration
title_short Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration
title_full Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration
title_fullStr Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration
title_full_unstemmed Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration
title_sort neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration
publisher Wolters Kluwer Medknow Publications
publishDate 2023
url http://eprints.utm.my/106032/1/MohdAizuddinMohd2023_NeuroprotectiveEffectsofExogenousBrainDerived.pdf
http://eprints.utm.my/106032/
http://dx.doi.org/10.4103/1673-5374.346546
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