Low Vision News: Edition 1 with Dr. Chen

Dong Feng Chen, Ph.D., M.D. is Assistant Professor of Ophthalmology at Harvard Medical School and is the lead investigator in the optic nerve regeneration study at the Schepens Eye Research Institute in Boston MA.

Follow up:

We are happy to welcome her as our first featured scientist.

LVN EDITOR-Your work is so important for millions of people suffering from optic atrophy, glaucoma, trauma and stroke. How do you start an investigation of this magnitude?

Dr. Chen- I have been interested in CNS nerve regeneration for a long time. I worked at the Massachusetts Institute of Technology, where I became interested in spinal cord injury. The optic nerve was a very accessible place to begin my study. The first part of my study was to find molecular mechanisms that prevent CNS axon regeneration

LVN EDITOR- Isn’t it a medical fact that if you cut or damage an adult CNS nerve like the spinal cord or optic nerve it will not grow back?

Dr. Chen- As a matter of fact, lower vertebrate animals, such as fish and frog, can regenerate damaged CNS neurons. However, higher vertebrates, such as mammals or birds, do not have the capacity to regenerate CNS neurons in the adult. I began my investigation by studying mice because the technology of genetic engineering was only available in mice at the time I started my work at MIT. This technique offers a powerful tool for studying gene regulation in CNS regeneration or any other biological processes. While it is known that a severed embryonic optic nerve will regenerate, we discovered that mouse embryos which can regenerate the optic nerve have a gene present during the embryonic stage that allows the nerve to heal. Based on this information, we generated a genetically engineered mouse line that forced the expression of this gene, Bcl-2, in CNS neurons throughout life. This genetic modification in mice can be passed from one generation to another, creating many generations of transgenic mice. However, forced expression of Bcl-2 gene alone in an adult mouse eye did not produce the same regenerative response. This is because adult tissues surrounding the nerve also contain glial scar and myelin, which can block nerve regeneration. Optic nerve regeneration cannot be induced by the forced expression of intrinsic Bcl-2 factor alone if the glial scar and myelin tissues are present.

LVN EDITOR- How do you know that the optic nerve is repaired?

Dr. Chen- This can be tested through two methods: first, by morphology. When a dye is injected into the eye with a severed optic nerve, the dye travels up the nerve and pools and stops at the point that the nerve is cut. If the nerve tissue regenerates, the dye will continue traveling up the optic nerve; second, by examining visual function in mice. This is not a simple task. We are still in the process of trying to prove that mice regain their vision after optic nerve regeneration.

LVN EDITOR- When you have a nerve as complex as the optic nerve, how do you maintain alignment of all of the axons?

Dr. Chen- That is a very good question. It appears that the axons can align themselves to pre-existing pathways. I believe that there will also be some cortical involvement. Similar to what is happening in the development, connections that are useful are maintained, while connections that are not useful don’t.

LVN EDITOR- How do you know that you have restored functional vision?

Dr. Chen- First, the Visually Evoked Potential (VEP), the electrical signal that is produced by photoreceptors and travels through the optic nerve looks normal. Second, a functional/behavioral assessment indicates that the mouse can see.

LVN EDITOR- How soon will you be ready to start human trials?

Dr. Chen- We are not ready to start human trials yet. Before we start human trials, we will need to develop a drug or gene delivery method that allows human recombinant DNA to produce the molecule necessary to make the nerve grow, because the transgenic technology cannot be applied to the human. Once the drug or gene delivery method is developed, we will still have to work out the pre-clinical toxicity profile and drug efficacy before we can find out if the human optic nerve will regenerate as in the mouse.

LVN EDITOR- Are there any other projects of interest to our readers that are closer to human trials?

Dr. Chen- Yes there is another project we are working on. We are trying to grow new photoreceptors from dormant stem cells that already exist in the eyes. We found in mice that these endogenous stem-like cells have the capacity to grow retinal tissues under certain stimulation. By harvesting these stem cells and transplanting them back into the eye, we were able to make them to generate new photoreceptors. We feel this technique is much simpler to reproduce in humans then our optic nerve regeneration study, because it takes the advantage of the dormant regenerative potential of our own body.

LVN EDITOR- Thank you so much for sharing your work with our readers. We look forward to speaking with you again in the future for an update on your work. Once you start human trials, we would be happy to assist you. We hope you will check out our Comment section to see the response of our readers.