Nicotinamide treatment robustly protects from inherited mouse glaucoma
Nicotinamide adenine dinucleotide (NAD) is a key molecule in several cellular processes and is essential for healthy mitochondrial metabolism. We recently reported that mitochondrial dysfunction is among the very first changes to occur within retinal ganglion cells during initiation of glaucoma in D...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Communicative & Integrative Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19420889.2017.1356956 |
| _version_ | 1818619054477279232 |
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| author | Pete A. Williams Jeffrey M. Harder Brynn H. Cardozo Nicole E. Foxworth Simon W. M. John |
| author_facet | Pete A. Williams Jeffrey M. Harder Brynn H. Cardozo Nicole E. Foxworth Simon W. M. John |
| author_sort | Pete A. Williams |
| collection | DOAJ |
| description | Nicotinamide adenine dinucleotide (NAD) is a key molecule in several cellular processes and is essential for healthy mitochondrial metabolism. We recently reported that mitochondrial dysfunction is among the very first changes to occur within retinal ganglion cells during initiation of glaucoma in DBA/2J mice. Furthermore, we demonstrated that an age-dependent decline of NAD contributes to mitochondrial dysfunction and vulnerability to glaucoma. The decrease in NAD renders retinal ganglion cells vulnerable to a metabolic crisis following periods of high intraocular pressure. Treating mice with the NAD precursor nicotinamide (the amide form of vitamin B3) inhibited many age- and high intraocular pressure- dependent changes with the highest tested dose decreasing the likelihood of developing glaucoma by ∼10-fold. In this communication, we present further evidence of the neuroprotective effects of nicotinamide against glaucoma in mice, including its prevention of optic nerve excavation and axon loss as assessed by histologic analysis and axon counting. We also show analyses of age- and intraocular pressure- dependent changes in transcripts of NAD producing enzymes within retinal ganglion cells and that nicotinamide treatment prevents these transcriptomic changes. |
| first_indexed | 2024-12-16T17:31:23Z |
| format | Article |
| id | doaj.art-80f05564d60e46f3b8a73f3a43c4ff63 |
| institution | Directory Open Access Journal |
| issn | 1942-0889 |
| language | English |
| last_indexed | 2024-12-16T17:31:23Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Communicative & Integrative Biology |
| spelling | doaj.art-80f05564d60e46f3b8a73f3a43c4ff632022-12-21T22:22:56ZengTaylor & Francis GroupCommunicative & Integrative Biology1942-08892018-01-0111110.1080/19420889.2017.13569561356956Nicotinamide treatment robustly protects from inherited mouse glaucomaPete A. Williams0Jeffrey M. Harder1Brynn H. Cardozo2Nicole E. Foxworth3Simon W. M. John4The Howard Hughes Medical Institute, The Jackson LaboratoryThe Howard Hughes Medical Institute, The Jackson LaboratoryThe Howard Hughes Medical Institute, The Jackson LaboratoryThe Howard Hughes Medical Institute, The Jackson LaboratoryThe Howard Hughes Medical Institute, The Jackson LaboratoryNicotinamide adenine dinucleotide (NAD) is a key molecule in several cellular processes and is essential for healthy mitochondrial metabolism. We recently reported that mitochondrial dysfunction is among the very first changes to occur within retinal ganglion cells during initiation of glaucoma in DBA/2J mice. Furthermore, we demonstrated that an age-dependent decline of NAD contributes to mitochondrial dysfunction and vulnerability to glaucoma. The decrease in NAD renders retinal ganglion cells vulnerable to a metabolic crisis following periods of high intraocular pressure. Treating mice with the NAD precursor nicotinamide (the amide form of vitamin B3) inhibited many age- and high intraocular pressure- dependent changes with the highest tested dose decreasing the likelihood of developing glaucoma by ∼10-fold. In this communication, we present further evidence of the neuroprotective effects of nicotinamide against glaucoma in mice, including its prevention of optic nerve excavation and axon loss as assessed by histologic analysis and axon counting. We also show analyses of age- and intraocular pressure- dependent changes in transcripts of NAD producing enzymes within retinal ganglion cells and that nicotinamide treatment prevents these transcriptomic changes.http://dx.doi.org/10.1080/19420889.2017.1356956GlaucomaNAD+nicotinamideaxon degenerationretinal ganglion celloptic nerve head cupping |
| spellingShingle | Pete A. Williams Jeffrey M. Harder Brynn H. Cardozo Nicole E. Foxworth Simon W. M. John Nicotinamide treatment robustly protects from inherited mouse glaucoma Communicative & Integrative Biology Glaucoma NAD+ nicotinamide axon degeneration retinal ganglion cell optic nerve head cupping |
| title | Nicotinamide treatment robustly protects from inherited mouse glaucoma |
| title_full | Nicotinamide treatment robustly protects from inherited mouse glaucoma |
| title_fullStr | Nicotinamide treatment robustly protects from inherited mouse glaucoma |
| title_full_unstemmed | Nicotinamide treatment robustly protects from inherited mouse glaucoma |
| title_short | Nicotinamide treatment robustly protects from inherited mouse glaucoma |
| title_sort | nicotinamide treatment robustly protects from inherited mouse glaucoma |
| topic | Glaucoma NAD+ nicotinamide axon degeneration retinal ganglion cell optic nerve head cupping |
| url | http://dx.doi.org/10.1080/19420889.2017.1356956 |
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