Researchers have successfully transplanted human microglia cells into mouse retina to create a model that could be used to test new treatments for incurable eye diseases. The research, published in eLife, offers solid data demonstrating the potential for microglial replacement therapy to treat retinal and central nervous system diseases.
What are microglia and why are they important?
Microglia are the innate immune cells of the central nervous system, which includes the retina, and play essential roles in the normal development of nerves and nerve connections (synapses). They also can play a less desirable role – driving the development of brain and eye diseases, such as age-related macular degeneration (AMD), glaucoma, diabetic retinopathy and uveitis (inflammation of the eye).
Under normal conditions, microglia survey environmental changes to maintain normal retinal function. Under pathological conditions, they quickly respond to injuries, but could also become inappropriately activated, grow in number, and migrate into surrounding tissues. This can lead to chronic inflammation, neuronal death, and vision loss.
How did the researchers create the new model?
The researchers grew microglia from a type of stem cell called human induced pluripotent stem cells (hiPSCs). They then performed several tests to determine whether their cultivated microglia cells functioned as typical immune cells and then transplanted them into mice retina.
To test their theory, the researchers first administered a drug to eradicate the existing population of microglial cells. They then injected the human microglia cells into the mouse retina. After four weeks, they observed that the human microglia cells had successfully integrated into the mouse retina and displayed normal morphology and function.
The researchers also tested whether the human microglia cells could respond to injury and inflammation in the mouse retina. They induced retinal damage by injecting a chemical that targets the mitochondria, the energy-producing organelles of the cells. They found that the human microglia cells migrated to the site of injury and produced inflammatory molecules, similar to how native microglia would react.
What are the implications and limitations of the study?
The study demonstrates that human microglia cells derived from hiPSCs can be successfully transplanted into mouse retina and function normally. This provides a new platform for studying human microglia biology and pathology in vivo, as well as testing potential therapies for retinal and central nervous system diseases.
However, the study also has some limitations. For example, the researchers did not test whether the human microglia cells could protect or restore vision in the mouse model. They also did not compare the effects of different sources or types of human microglia cells, such as those derived from patients with specific eye diseases. Furthermore, they did not evaluate the long-term safety and stability of the human microglia transplantation.
Therefore, more research is needed to address these issues before applying this approach to human clinical trials.
