Cited by 232Glaucoma and retinal disordersCell death mechanisms and regulationRetinal Development and Disorders

Apoptosis of Retinal Ganglion Cells in Glaucoma

Nickells, Robert W·1999·Survey of Ophthalmology

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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Crossref · 10.1016/s0039-6257(99)00029-6

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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).”

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Authors
Nickells, R. W.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
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

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