March 2010




Dormant cells can regain function

by Maxine Lipner Senior EyeWorld Contributing Editor


Rip Van Winkle-like retinal cells deprived of oxygen can return to normal

Having blood supply to the retina restricted for a time is not necessarily the death knell for cells, according to Jeremy Nathans, M.D., Ph.D., professor of molecular biology, genetics, neuroscience, and ophthalmology, Johns Hopkins University School of Medicine, Baltimore. In a recent study published in the October 2009 issue of Cell, investigators led by Dr. Nathans found that retinal cells in the mouse retina could survive for many months and later recover even when they had not received enough blood for a time.

Sleeping retina

Dr. Nathans termed the discovery an accidental one—a bit of a lark. Investigators noticed that in the absence of certain proteins intra-retinal capillaries were not made, and the retina appeared to be in a sleeping stage. “The retina tends to be in a sort of Rip Van Winkle-like state,” Dr. Nathans said. “Amazingly, the retina looks quite normal; essentially the cells aren’t dying in appreciable numbers as far as we can tell, but they’re not working either.” Investigators found that the electroretinogram showed that the photoreceptors were working just fine. Since the retina is a three-layered structure akin to a stack of pancakes, Dr. Nathans sees this as making a lot of sense. “The photoreceptors are in the outermost layer, the part farthest from the front of the eyeball,” Dr. Nathans said. “It turns out that all the blood supply for that outermost layer comes from a different set of blood vessels. It’s a set that is not in the retina, and the oxygen diffuses toward the retina and supplies the photoreceptors.” As a result, Dr. Nathans said it isn’t surprising that these cells would be protected if the retinal blood supply is hampered. The cells on the innermost layer also appear to be doing alright. “Although the blood vessels can’t grow in the retina they still grow quite well on the surface of the retina,” Dr. Nathans said. “The ones that are closest to the surface seem to be doing just fine.”

Investigators found good evidence to substantiate this. “We know that some of the cells are actually directly sensitive to light and control the constriction of the pupil,” Dr. Nathans said. “When we look at the pupil constriction by these mice it is nearly normal.” However, other signals clearly don’t reach the brain. For example, investigators found that while normal mice can track an object, these mutant mice without intra-retinal capillaries can’t track it at all. “When we look at the electrical signal, we see that the signal that comes from the middle layer of retinal cells is completely silenced,” Dr. Nathans said.

Bringing dormant cells to life

However, many cells that appeared dormant were brought back to life when put in the proper milieu. When investigators took the retina from the mouse and placed it in a dish replete with oxygen, glucose, and other substances necessary for growth they found that the cells began to function once again. “Using electrodes, we asked whether their electrical response to light was normal or not,” Dr. Nathans said. “The answer is that it’s normal.” Investigators saw this as very heartening. “Our conclusion is that the cells can come back to life as long as they have everything they need in terms of oxygen and glucose,” Dr. Nathans said. “I think that there is probably a window of blood supply or oxygenation of neurons that is short of the point where they can function normally but is not at the point where they are going to die.” From a clinical perspective he sees this as possibly explaining some miraculous visual recoveries. “I think that it may explain the observation that some people with retinal artery occlusion who suffer a sudden loss of vision because their vascular supply has been occluded can recover some vision after a period of time,” Dr. Nathans said. “I think that some retinal cells are in this state of hibernation, and maybe the same is true of people who over time show some recovery from stroke.”

Of course there may be other contributing factors as well. “Part of it may be that the brain relearns different tasks and different neurons can take over the region that was injured,” Dr. Nathans said. “But I think that another part of it may be that during the acute phase of the stroke there are some neurons that are alive but are nonfunctional.” These cells may later recover. “Eventually, when the blood supply is restored under the normal vascular system or when compensatory vessels grow in and restore the blood supply, some of those neurons come back to life in terms of function,” Dr. Nathans said.

Editors’ note: Dr. Nathans has no financial interests related to his comments.

Contact information

Nathans: 410-955-4679,

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