Apoptosis of Retinal Ganglion Cells in Glaucoma
Abstract
Apoptosis is a genetically controlled form of cell death that ganglion cells undergo during normal development of the retina and in diseases affecting the optic nerve, such as glaucoma. This mechanism of cell death is controlled by specific genes and their products that are activated in the dying cell. To date, the mechanism of ganglion cell apoptosis is poorly understood, but research on cell death in other areas has provided a blueprint for the study of dying ganglion cells in animal models. Extensive research of the genetic pathways of apoptosis of neurons, in general, has yielded new information about the principal genes that are involved in this process. This review is meant to survey the major genetic players that are active in neuronal cell death and discuss their possible roles in retinal ganglion cells. One of the primary regulatory steps is the activation of the tumor-suppressor protein, p53. This protein functions as a transcription factor that can up-regulate the expression of the proapoptotic gene bax and down-regulate the expression of the antiapoptotic gene brl-2. Changes in the concentrations of these gene products can further stimulate apoptotic events, including changes in mitochondria that ultimately lead to the activation of a family of cysteine proteases called caspases that digest the dying cell from within. An understanding of the genetic pathways of apoptosis may lead to the design of new treatments that could prevent its activation or arrest the process when started.
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These glaucoma-related alterations can lead to secondary damage such as excitotoxicity, neurotrophin deprivation, oxidative damage, mitochondrial dysfunction, and eventually retinal ganglion cell death.
“These alterations can lead to secondary damage such as, excitotoxicity, neurotrophin deprivation, oxidative damage, mitochondrial dysfunction, and eventually RGC death (Nickells, 1999; Gallego et al., 2012).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Nickells, 1999
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The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
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Martin, K. R. G., Quigley, H. A., Zack, D. J., Levkovitch-Verbin, H., Kielczewski, J., Valenta, D., Baumrind, L., Pease, M. E., Klein, R. L., & Hauswirth, W. W. (2003) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.02-1332 · Cited by 362 · see citing works
- Authors
- Nickells, R. W.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Nickells, Robert W
- ORCID
- Nickells, Robert W
- Venue
- Survey of Ophthalmology
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 43
- Pages
- S151-S161
- ISSN
- 0039-6257 (ISSN-L)
- OpenAlex
- W2004260482
- Cited by
- 232
- References
- 95
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 7 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 10
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Survey of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- apoptosis, retinal ganglion cells, glaucoma, neuronal cell death, p53, Bax, caspases, mitochondrial dysfunction, optic nerve
- MeSH terms
- Animals, Glaucoma, Humans, Mitochondria, Proto-Oncogene Proteins, Retinal Ganglion Cells, Genetic Therapy, Gene Expression, Tumor Suppressor Protein p53, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Genes, bcl-2, Caspases, bcl-2-Associated X Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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