Material below summarizes the article Overexpression of Brain-Derived Neurotrophic Factor Protects Large Retinal Ganglion Cells Following Optic Nerve Crush in Mice, published on January 5, 2017, in eNeuro and authored by Liang Feng, Zhen Puyang, Hui Chen, Peiji Liang, John B. Troy, and Xiaorong Liu.
Disorders of the visual system often involve neuronal loss in the retina and in the higher visual centers of the brain, which eventually leads to low vision and blindness. In many cases, vision loss cannot be restored because neuronal death is irreversible.
For example, glaucoma is a group of eye diseases characterized by a loss of retinal ganglion cells (RGCs), optic nerve defects, and atrophy, and afflicts more than 60 million people worldwide. RGC death may follow different paths with different forms of glaucoma, so experimental models have been developed to mimic these different forms. Rodent models of optic nerve crush have often been used to study rapid degeneration of RGCs, as well as their axon regeneration. Crush may not be a “true” model of glaucoma, but it is an optic neuropathy leading to RGC death and offers the advantage of investigation of rapid RGC loss and its underlying mechanisms within a short time.
Several recent studies, including ours, on morphological and functional degeneration of RGCs suggested that different types of RGCs exhibit different susceptibility to the disease insult. The recent advances in basic research on RGC development and function suggest that there are more than thirty mammalian RGC types, each with a unique function, structure, and axonal connections, providing a challenge to characterize how glaucoma affects different varieties of RGC.
In our current study, we applied a fluorescent fundus Micron III system to track the survival of one type of RGCs expressing green fluorescent protein (GFP) following optic nerve injury. The in vivo imaging system eliminated the sampling variations from mouse to mouse, a common concern in RGC quantification with fixed tissue. Furthermore, combined with genetically targeted manipulations in mice, the in vivo imaging system provides an opportunity to examine the molecular and cellular mechanisms underlying the progressive RGC loss following injury.
Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins essential for neuronal survival and function in the central nervous system. Growing evidence, including our studies, support that BDNF can act as a protective agent to maintain retinal health. However, incomplete protection or insufficient rescue by BDNF were often observed in different models of optic neuropathy.
Therefore, we decided to take a genetic approach to upregulate BDNF in the mouse retina and then examine the effect of BDNF upregulation on RGC survival following optic nerve injury. We focused on one subtype of RGC with large soma expressing GFP transgene, which accounts for about 11 percent of the total SMI-32 positive RGCs. The median survival time of this subgroup of SMI-32 cells was one week following nerve injury in wild-type control mice, but two weeks when BDNF was up-regulated. We also studied changes in axon number using confocal imaging, confirming first the progressive loss reported previously for wild-type mice and demonstrating that BDNF upregulation extended axon survival.
In other words, our studies suggest that BDNF encouraged the survival of large-soma RGCs following acute optic nerve injury.
Many important questions remain unanswered. Different neuroprotective agents have targeted the multiple pathogenic mechanisms that result in axonal degeneration and RGC death, which include anti-apoptotic strategies, anti-excitotoxic agents, stem cells, and more. Given the diverse RGC type and that each type matures and functions differently, each type may activate a different combination of pathogenic pathways in diseased condition. The partial or incomplete protective effects observed in previous studies could be also due to the type-specific protection by individual neuroprotective agent.
Better understanding of the type-specific RGC death and its underlying neuroprotective mechanisms will lead to the development of therapies targeted to specific RGC type(s) in order to achieve full protection of vision for glaucoma patients.
Visit eNeuro to read the original article and explore other content. Read other summaries of JNeurosci and eNeuro papers in the Neuronline collection SfN Journals: Research Article Summaries.
Overexpression of Brain-Derived Neurotrophic Factor Protects Large Retinal Ganglion Cells After Optic Nerve Crush in Mice. Liang Feng, Zhen Puyang, Hui Chen, Peiji Liang, John B. Troy, Xiaorong Liu. eNeuro Jan 2017 DOI: 10.1523/ENEURO.0331-16.2016
About the Contributor
