Tuesday, November 14, 2006

Let there be light and there was ....

The optic nerve conveys the sensory information gathered by the retina of the eyes to the visual cortex in the brain through a pretty complicated pathway. Now what happens when part of the optic nerve has degenerated or atrophied due to diseases like glaucoma (Early signs of glaucoma occurs when passages that filter and exchange fluid within the eye are blocked, internal fluid eye pressure to increase. If left untreated, the increased pressure can cause permanent damage to the optic nerve) or due to other genetic causes. The optic nerve axons do not have the power to automatically regenerate and repair itself after an injury of this nature.

Researchers at the Benowitz lab at Harvard Medical School (Drs. Steven Leon and Yuqin Yin) discovered that producing an inflammatory reaction in the eye causes macrophages to secrete proteins (hereinafter referred to as MDPs or Macrophage Derived Proteins) that enable retinal ganglion cells (RGCs) to survive axon damage and regenerate their axons through the optic nerve.

"Dr. Yin developed a cell culture model of the adult retina and discovered that axon regeneration requires 3 components: a low molecular weight factor that is constitutively present in the eye, elevated intracellular cAMP, and a protein that is secreted by macrophages.

"They found out that the carbohydrate mannose helps fulfill the low molecular weight criteria. They also found that an MDP called oncomodulin displays a high affinity for binding to cell surface receptors on RGCs. When this was delivered through slow release microspheres that elevated intracellular cAMP in RGCs, the end result seems to be dramatic axon regeneration of a mature optic nerve (of course this is a mouse model, but we seem to be fairly successful at replicating things like this onto humans). This has a lot of implications to people who have chronic blindness as a result of optic nerve damage following glaucoma based elevated eye pressure. From "http://www.medicalnewstoday.com/medicalnews.php?newsid=43428"

"When oncomodulin was added to retinal nerve cells in a Petri dish, with known growth-promoting factors already present, axon growth nearly doubled. No other growth factor was as potent. In live rats with optic-nerve injury, oncomodulin released from tiny sustained-release capsules increased nerve regeneration 5- to 7-fold when given along with a drug that helps cells respond to oncomodulin. Yin, Benowitz and colleagues also showed that oncomodulin switches on a variety of genes associated with axon growth. Benowitz, the study's senior investigator, believes ncomodulin could someday prove useful in reversing optic-nerve damage caused by glaucoma, tumors or traumatic injury. In addition, the lab has shown that oncomodulin works on at least one other type of nerve cell, and now plans to test whether it also works on the types of brain cells that would be relevant to treating conditions like stroke and spinal cord injury.

Please see a pdf handout at the following site:

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