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phila, is also defective in all patients of one subtype of
Several years ago, Dr. Charles Laird of the University of
Recently, Dr. Stuart Schreiber of Harvard University, a grantee
For many years, Dr. Glenn Dryhurst of the University of Oklahoma has been examining the chemistry of a basic chemical grouping, called the indole moiety, found in certain proteins, including the neurotransmitter serotonin. Recently, he observed unusual oxidized forms of the indole moiety of serotonin in the spinal fluid of people with Alzheimer's disease, but not in that of matched controls. This finding has led Dr. Dryhurst to postulate that this unusual indole chemistry could be toxic and might help account for the degeneration of brain tissue seen in Alzheimer's disease. Dr. Dryhurst and others are currently investigating this possi-bility, hoping to further our understanding of this devastating disease.
Just as there is no way of predicting which fundamental studies will uncover findings critical to progress on particular diseases, it is equally difficult to estimate how long the process of turning a basic finding into a clinical application will take. However, there is no doubt that the availability of the tools of molecular biology has, in many instances, accelerated this process. There are instances of this taking only a few years, while in other cases, where the problem is less tractable, it might take far longer.
NATIONAL EYE INSTITUTE
STATEMENT OF DR. CARL KUPFER, DIRECTOR
BUDGET REQUEST Senator HARKIN. Dr. Kupfer, your fiscal year 1992 budget request is $272.2 million, 7.5 percent more than 1991.
The Eye Institute's new vision plan, which encompasses your research agenda for the next 5 years, is a subject we hope to hear more about today. Dr. Kupfer, please proceed.
Dr. KUPFER. Thank you, Mr. Chairman.
I would like to briefly summarize my opening statement. There is increasing blinding eye disease especially in older Americans. In 1995, it is estimated that there will be about 34 million Americans over the age of 65. Almost 2 million of them will have visual disability from a condition called age-related maculopathy, which is the leading cause of new adult blindness in the United States. That means about 1 out of 17 older Americans will have a visual problem from this condition. As an ophthalmologist, it is very distressing to me that at the present time we really do not have any way of treating the vast majority of them successfully. There is a small subgroup that we can help, but for all practical purposes, this is a very serious problem indeed.
Toward this end, we have begun a study on age-related eye disease in which we want to collect basic information on who is at risk to develop this condition, and at a later date, perhaps in a year or so, to begin to look at some treatments that might be of benefit. This is one of the overwhelming concerns that we have at this present time.
PROGRESS AND OPPORTUNITIES On a more optimistic note, we have made progress against nearsightedness, myopia. This is a condition which affects some 60 million Americans. Basically, it results when the eye is too large to allow the images to be focused sharply on the retina. We now have very important evidence from animal models that there are neurotransmitters in the retina which apparently play a very important role in the growth of the eye. In the next few years, we are going to be able to see this basic laboratory information turned into a treatment to slow down the progression of nearsightedness, or myopia.
Two clinical trials have reached a very satisfactory conclusion in the past year. We now know that there is a way to determine the amount of surgery that should be done in a child whose eyes turn in. A very simple test can be done before the surgery to determine exactly how much surgery should be done. In doing this test, we have improved the success rate of surgery to straighten eyes so that the need for a second operation is markedly reduced.
The second clinical trial has been the question: How safe and effective is laser treatment of glaucoma. This treatment has often been reserved later on in the therapy of glaucoma because one was not sure whether it was both safe and effective. We have just concluded 2 years of a 5-year study, and early indications are that laser treatment is both safe and effective in lowering the pressure in the eyes. This study will, of course, continue.
We are carrying out a clinical trial on the treatment of involvement of the retina, the seeing part of the eye, in patients with AIDS. Some 25 percent of all AIDS patients will eventually develop a viral infection of the retina which can lead to blindness. We are now comparing two different drug therapies for slowing down the loss of vision in such patients, if not preventing it.
VISUAL BRAIN SYSTEM Finally, I would like to end with some considerations about something you heard several people talk about, and that is the Decade of the Brain. We are particularly focusing our attention on the visual system, which provides almost 40 percent of all the input to the brain, in three areas.
The first is that we want to develop techniques to prevent degenerative changes in the brain. We now have some basic information on how to prevent degeneration in the retina which is part of the brain. This is accomplished with the use of what is called a basic fibroblast growth factor. This is a major stride forward in which the possibility of preventing degeneration can be approached.
The second interest we have is whether brain tissue can be transplanted. Our scientists have shown for the first time that retinal tissue can be transplanted and take and set up connections.
Finally, we want to find ways to maintain the regenerative capacity of tissue in the brain in the visual system. We know that in the very young, this regenerative capacity is present, but as the individual matures, it is lost. We are trying to find ways to maintain this regenerative capacity. We have now found that there is a group of proteins called growth associated proteins which, if we can keep them active, will allow brain tissue to regenerate.
PREPARED STATEMENT So, we are very much involved in brain research, utilizing the visual system to make a major impact on preventing degeneration, maintaining the possibility of transplantation, and keeping regenerative capacity at a maximum.
As you mentioned, the budget request for fiscal year 1992 is $272,260,000.
I would be happy to answer any questions. (The statement follows:)
STATEMENT OF DR. CARL KUPFER
Mr. Chairman, It is always a pleasure to testify before this Committee and share some of the many research advances that each year help us better understand the marvelous complexity of the human eye. Many have led to great improvements in our ability to prevent, diagnose, and treat blinding eye and visual disorders. This year, however, I would like to begin my comments by bringing to your attention a disturbing new finding. Based on projections
from a recent NEI-supported survey, as many as one million Americans may now
While there are many causes for blindness, one of the most significant is
aging. Because older Americans now represent a rapidly growing segment of our
society, age-related eye diseases--such as cataracts, glaucoma, diabetic
retinopathy, and macular degeneration-- have correspondingly increased in
importance as causes of blindness. In fact, it may be that blinding agerelated eye diseases are more prevalent today simply because more Americans
now live long enough to develop then.
Without increased understanding of the aging eye, I believe further increases in blindness will occur. To help bring about this understanding,
the Institute now supports a number of relevant basic and clinical
investigations. For example, we have recently begun the Age-Related Eye
Diseases Study (AREDS), a multi-center research project that will follow the
development and progression of cataracts and age-related macular degeneration
in a group of older Americans. Since the AREDS is the first large-scale
attempt to track the natural history of these diseases, the NEI hopes that the
study will help provide the scientific basis for future prevention strategies.
Although age-related eye diseases represent one of the NEI's most
important areas of current and future investigation, the Institute also faces
several other significant research challenges. I have mentioned in previous
years that nearly 40 percent of all sensory input into the brain originates
from the eye.
If scientists can begin to understand better the remarkable
complexities of the visual system, this knowledge can be applied to help
unlock age-old mysteries of not only human behavior, learning and memory, but
also neurological disease.
For this reason, NEI programs are an integral part
of the "Decade of the Brain" initiative.
For example, it is well established that brain tissue loses its ability
to divide and grow immediately after birth. Because researchers have been
unable to learn the biological secret that would allow them to regenerate
brain cells, serious neurological injury can have devastating consequences on
basic human skills, such as vision, speech, memory, and movement. Recently, however, NEI-supported vision researchers isolated two growth factors within the retina, which is considered to be a part of the brain. One of these natural compounds, basic fibroblast growth factor (bFGF), actually prevented animal retinal cells from degenerating in preliminary studies, and thus prevented severe visual loss and blindness. It is reasonable to assume that the continued study of retinal growth factors could provide the underpinning for similar work on other brain cells.
Studies aimed at transplanting retinal cells also show considerable promise for brain research. Although the successful transplantation of brain cells would provide enormous therapeutic benefits to people affected by brain disorders or trauma, scientists have been unable to accomplish this in laboratory animals. However, an NEI - supported team of vision researchers report the successful transplantation of retinal cells in animals. Again, it is possible that the future refinement of such work in retinal cells may provide many of the keys that will one day allow us to apply this to the brain.
On another research front, I am pleased to report that vision researchers have begun to identify the mechanisms underlying corneal scarring. When the
cornea--the eye's transparent, outermost tissue-- is severely damaged, it
becomes irreversibly clouded, resulting in varying degrees of vision loss. Because corneal diseases account for nearly 25,000 new cases of blindness in
this country each year, a greater understanding of this problem is essential
to vision research.
NEI - supported scientists have recently identified and cloned the genes
that cause corneal scarring. With this finding, scientists can now work to
develop drugs that block the activation of these genes, reduce corneal
clouding, and thus minimize vision loss due to corneal injury. Moreover,
since the cornea has historically played a central role in the study of
general wound healing, scientists may also be able to study these genes to