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phila, is also defective in all patients of one subtype of
Fanconi Anemia. Dr. Boyd's discovery provides a potentially
valuable tool for identifying and isolating the defective gene
in humans and for developing appropriate mammalian model systems
to investigate possible treatment for Fanconi Anemia patients.

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Several years ago, Dr. Charles Laird of the University of
Washington in Seattle developed a hypothesis about the genetic
basis of the most common inherited form of mental retardation,
known as the fragile-X chromosome syndrome. Dr. Laird's work in
Drosophila led him to conclude that the syndrome was caused by
the abnormal activation of a gene or genes. Now scientists here
and abroad have found evidence in humans substantiating
Dr. Laird's theory. This should permit the development of diag-
nostic tools and, perhaps, even treatments for this disorder.

Recently, Dr. Stuart Schreiber of Harvard University, a grantee
whose research focused on synthesizing molecules of immunologi-
cal importance, found during the course of his work a series of
small molecules that bind to the AIDS virus at the site where
the virus would normally bind to and infect the T cells of the
immune system.

Now Dr. Schreiber and others are building on
this work in order to determine whether these or similar mole-
cules could be used to disrupt the infective stages of the AIDS


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 postu-
late 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 under-
standing of this devastating disease.

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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.

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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.


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.


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.

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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:]


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

be blind.

While there are many causes for blindness, one of the most significant is


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 age

related eye diseases are more prevalent today simply because more Americans

now live long enough to develop them.

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


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 tne 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 For example, it is well established that brain tissue loses its ability

of the "Decade of the Brain" initiative,

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.


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


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.


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

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