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Updated: Feb 12, 2026

Single-cell RNA-Seq of Defined Subsets of Retinal Ganglion Cells
Published on: May 22, 2017
BCL2L1 (BCL-X) promotes survival of adult and developing retinal ganglion cells
Jeffrey M Harder1, Qian Ding, Kimberly A Fernandes
1Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Abstract:
The Bcl-2 family is responsible for regulating cell death pathways in neurons during development, after injury and in disease. The activation of the pro-death family member BAX is often the final step before cell death in neurons. Pro-survival family members such as BCL-X (BCL2L1) act to inhibit BAX activation. Overexpression studies have suggested that BCL-X could play an important physiological role in mediating neuronal viability. Loss-of-function studies performed in vivo have implicated BCL-X as a mediator of neuronal survival during the early stages of neurodevelopment. To assess whether BCL-X is needed to promote the survival of neurons in the central nervous system throughout life, Bcl-x was conditionally removed from the optic cup or throughout the adult mouse. During development BCL-X was required for the survival of differentiating retinal ganglion cells (RGCs) leading up to their normal window of developmental death. Despite its expression in adult RGCs, BCL-X was not required for maintaining RGC viability in adult retinas. However, the loss of BCL-X in adult RGCs did significantly increase the rate of death of RGCs after axonal injury. Thus, in developing and injured RGCs there appears to be an active cell survival program preventing neuronal death.
Insights
The Bcl-2 family protein BCL-X (BCL2L1) is crucial for neuronal survival during development and after injury. However, it is not essential for maintaining adult neuron viability in the absence of stress.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The Bcl-2 family regulates neuronal cell death pathways.
- BAX activation is a critical step in neuronal apoptosis.
- BCL-X (BCL2L1) is a pro-survival member that inhibits BAX.
Purpose of the Study:
- To determine if BCL-X is required for neuronal survival throughout life.
- To investigate the role of BCL-X in developing and adult central nervous system neurons.
Main Methods:
- Conditional removal of Bcl-x in the developing optic cup and adult mouse.
- Assessment of neuronal survival in retinal ganglion cells (RGCs).
- Evaluation of RGC viability after axonal injury.
Main Results:
- BCL-X is essential for the survival of differentiating RGCs during development.
- BCL-X is not required for maintaining RGC viability in adult retinas.
- Loss of BCL-X significantly increases RGC death after axonal injury.
Conclusions:
- BCL-X plays a critical role in neuronal survival during specific developmental windows and in response to injury.
- Adult RGCs possess alternative survival mechanisms independent of BCL-X under normal conditions.
- Targeting BCL-X may be relevant for promoting neuronal survival after CNS injury.
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