I\’m standing in a quiet hallway in Biological Sciences II and about five feet away from me through an open door is a $250,000 electron microscope. I\’m looking at it wistfully and it\’s looking at something very small – or it would be, if it were turned on.

People will go to great lengths to see what they couldn\’t before. That\’s what this place is all about.

One out of every 10 people over the age of 60 will lose all or part of their vision to the eye disease known as age-related macular degeneration. Six years ago, researchers at UCSB set out to discover why. With $10,000 of seed money from the Office of Research and the blessing of the Neuroscience Research Institute, Don Anderson and former USC medical professor Lincoln Johnson started the Center for the Study of Macular Degeneration (CSMD).


The emerging theory of macular degeneration at CSMD is novel and far removed from the rest of the medical establishment, where researchers have mainly attempted to treat the symptoms, rather than discover the causes of macular degeneration, often referred to as AMD.

\”Back in 1995, there was very little, if any, organized research that was aimed at looking at the disease from a biological standpoint. … We seized that opportunity and I think we\’ve come a fair distance toward characterizing the process that goes on at a cellular level,\” Anderson says.

As you read this newspaper, the front of your eye is projecting an image of the paper onto your retina – a screen of cells at the back of your eyes. The cells that make up the retina are called photoreceptor cells, often referred to as \”rods\” and \”cones.\” They tell the brain about the image they are receiving by passing information along the optic nerve. Photoreceptor cells require huge amounts of energy to survive, so they get a little help from other places. Another underlying layer of cells known as the retinal pigmented epithelium (RPE) nourishes these photoreceptor cells.

The trouble begins, say CSMD scientists, when some of these RPE cells die and the body mounts a local inflammatory response similar to the way it might deal with a splinter or small cut. This reaction leaves protein deposits next to the RPE. The deposits interfere with the function of the surrounding RPE cells, which become distressed, reinforcing the inflammatory response.

And the cycle begins. Cells die, and inflammatory response begins. This leaves behind debris, which kills more cells, which starts another round of inflammation, ad nauseam.

Eventually, the deposits left by the body\’s inflammatory responses build up and form larger structures called drusen. Drusen is a borrowed term. It\’s German for \”plaques\” and ophthalmologist for \”bad news.\” Too many of these deposits cause permanent damage to the RPE. Without their nurse cells, the photoreceptor cells in the eye begin to die off.

When the photoreceptor cells die in an area of the retina known as the macula – the area next to your optic nerve – a blind spot forms in your center of vision. To make matters worse, if the disease continues to progress, the barrier between the drusen and the retina may break down and allow blood vessels to grow into the remaining space.

These blood vessels tend to bleed and are the cause of what is known as the \”wet\” form of macular degeneration. The \”dry\” form of AMD may take decades to progress, but the progression of the wet form is measured in days, and can lead to total blindness in the affected eye within a week.

The Research

Biologists at CSMD study human tissue cultures and human eyes. When a person donates corneas for transplant, the eye bank takes the front portion of the eye and gives the back portion to CSMD. The researchers study the molecular structure of drusen, how they affect and kill the cells that surround them, and how they arise from and contribute to macular degeneration.

\”The holy grail of the effort would be to understand why the RPE cells die in the first place,\” Anderson says. \”We know that the consequence of their death leads to local inflammation at that site, but what we don\’t know yet is why they die.\”

That\’s something no one knows. The biologists at CSMD have some good guesses though. A few things are clear. There is almost definitely a genetic component to the disease. This doesn\’t mean, however, that you can only get it if it runs in the family.

Macular degeneration also appears to bear a family resemblance to other autoimmune disorders in which the immune system attacks the body. Alzheimer\’s disease, for instance, leaves deposits similar to drusen.

Nutritional deficiencies may also be to blame for RPE death. Studies by the National Institutes of Health have shown that supplements of vitamins A, C, E and zinc can reduce a person\’s chances of developing AMD by as much as 25 percent.

Poor circulation is another suspect in RPE cell death. Since these cells have such a high metabolism, they require large amounts of oxygen. Poor circulation could deprive the RPE of the oxygen it needs to function. RPE cells may also just have such a high metabolic load that they die simply from being overworked.

Another theory contends that pigments in the RPE cells build up as a person ages, to the point that the cells become engorged and cannot function.

Scientists elsewhere have suggested that too much exposure to sunlight could be the cause of AMD. They contend that excess visible light could cause damage to the eye or that excess UV radiation could damage the photoreceptors. However, the statistical evidence for this theory is sorely lacking so far, Anderson says.

Any one of these could be the cause of RPE cell death. Or it might be something no one has thought of yet. In fact, there\’s nothing to say there is one single cause. It might be a result of any combination of these.

Finding a Cure

Once macular degeneration sets in, it is impossible to repair the damage that has been done. RPE and photoreceptor cells belong to the brain. They are neurons – a type of cell that cannot regenerate. In the wet form of AMD, laser surgeries are used by ophthalmologists to stop blood vessels from bleeding inside the eye. These surgeries can sometimes restore a bit of the patient\’s vision, but they also cause a buildup of scar tissue, which can make vision worse.

Doctors will need to take a different approach to ending AMD.

\”Currently people don\’t know they have this disease until they go their ophthalmologist,\” Johnson says. \”Their ophthalmologist looks in their eye and says \’Oh, you have lots of drusen in your eye.\’ They probably have not suffered any visual loss yet. The beginnings of the disease are there but they\’re not perceivable by the individual.\”

The CSMD researchers are looking for ways to treat AMD early on, before it becomes a problem and, in some cases, before it even happens.

\”We might be able to get to the point where, if a person\’s parents or siblings have macular degeneration, we can begin to test those people through a blood test or some other kind of assay,\” Johnson says. \”We can look for molecules there that will tell us whether or not you\’re likely to develop macular degeneration.\”

Because AMD appears to have nutritional links, vitamin supplements are one approach to preventing the disease.

Cigarette smoking also increases the risk of developing macular degeneration.

The disease results from the body\’s inflammatory reaction to RPE cell death, so CSMD researchers believe that anti-inflammatory drugs may also be a possible preventative measure. The deposits associated with Alzheimer\’s disease also have an inflammatory component. Therefore, biologists at the center are interested to see results from current studies of anti-inflammatory drugs on Alzheimer\’s patients.

\”Anti-inflammatories have been shown to be very effective in preliminary trials in Alzheimer\’s disease,\” Johnson says. \”We do see the number of incidents and rate of progression affected really significantly. Advil or Ibuprofen and other non-steroidal anti-inflammatories are very effective in preliminary results for Alzheimer\’s disease. The same trials have not been done for macular degeneration so we don\’t know whether or not the same effects will be seen in AMD patients.\”

A cure in the traditional sense isn\’t necessary because of the age at which AMD sets in.

\”Because it\’s a disease of aging, if you could delay the onset for 10 years or 15 years, then we\’d all have to live to be 100 before we developed the disease,\” Johnson says. \”That would essentially reduce it to being much less significant in terms of numbers.\”

The Center

Now, six years after CSMD opened its doors, similar research centers are opening at USC, John Hopkins, Harvard and MIT. Johnson left USC in 1995 to start the center at UCSB.

\”It was a good decision,\” he says. \”We\’ve made really tremendous strides that we could never have made without this kind of focused effort. It just wouldn\’t have happened. I don\’t have any regrets about leaving USC and coming here. The research has been great. We do it as a really collaborative effort.\”

\”In 10 years or so, my guess is that we\’ll probably be twice as large,\” Anderson says. \”But I don\’t think the goal is to attain a specific size. It\’s really to make rapid progress in certain specific areas that we think are important and we don\’t need large numbers of people to do that. But I think we\’ve already proven that.\”

As the biologists at CSMD come closer to understanding the origin of AMD, they hope to make progress in treating it as well.

\”Within five years, I would like to have some kind of model of the disease in the lab, whether that be an animal model or a cell culture model,\” Johnson says. \”Then we can begin testing specific drugs to retard the disease or inhibit its progression.\”

Outside of over-the-counter anti-inflammatories such as Ibuprofen, it will take some time for any drugs to make it outside of the lab.

\”Our view of AMD right now is really leading edge,\” Johnson says. \”It\’s not part of the conventional wisdom, so it may take a few years if we\’re correct before other people jump onboard. Once that happens, that might be when the time is right to advocate clinical trials … We\’re at a point where we\’re not ready to take anything to the clinic yet, but when we are, we\’ll be poised to do that.\”