News and Events
NEI FY2004 Budget Request--Congressional Testimony Statement before the Senate Appropriations Subcommittee on Labor-HHS-Education
Dr. Paul A. Sieving, Director
National Eye Institute
April 8, 2004
Mr. Chairman and Members of the Committee:
I am pleased to present the President's budget request for the National Eye Institute (NEI) for FY 2004. This budget includes $648 million, an increase of $16 million over the FY 2003 enacted level of $632 million comparable for transfers proposed in the President's request.
It is my privilege to be here as the Director of the NEI and tell you about progress laboratory and clinical scientists are making in combating blindness and visual impairment and about the unique opportunities that exist in the field of vision research.
Glaucoma leads to blindness from damage to the optic nerve of the eye. Glaucoma is often, but not always, associated with increased pressure within the eye caused by inadequate drainage of aqueous humor, the fluid within the eye that nourishes the cornea and lens. Results from two important clinical trials were reported during this past year. Investigators conducting the Ocular Hypertension Treatment Study found that eye drops used to treat elevated pressure inside the eye can be effective in delaying the onset of glaucoma. The study identified several significant risk factors that were associated with the development of glaucoma in study participants. These included personal risk factors, such as older age and African descent, as well as ocular risk factors, such as higher eye pressure and certain characteristics of the optic nerve and cornea. These results mean that treating people at higher risk for developing glaucoma may delay or possibly prevent the disease.
In a separate study researchers conducting the Early Manifest Glaucoma Trial, which was designed to compare the effect of immediate therapy to reduce pressure inside the eye with late or no treatment on the progression of newly detected open-angle glaucoma, found that progression was less frequent in the treated group (45 percent) than in the control group (62 percent), and occurred significantly later in treated patients. This finding demonstrates definitively that treatment to lower pressure inside the eye can slow glaucoma damage and subsequent vision loss.
Continuing the progress in the genetics of glaucoma reported last year by the finding of a new gene mutation that caused a form of adult-onset glaucoma, scientists recently reported identification of a human gene that is linked to a disease known as "low-tension" glaucoma. This form of glaucoma has the characteristic pattern of optic nerve degeneration but the elevation in pressure within the eye normally associated with this pattern of damage is not evident on clinical examination. The gene that was identified produces a protein that is expressed in a number of tissues including the brain and retina and is believed to have a significant neurological function. The identification of genes associated with glaucoma provides a tool to study the biochemical pathways leading to optic nerve degeneration, as well as giving insight into designing neuroprotective strategies. Additionally, NEI sponsored a meeting on ganglion cell and optic nerve degeneration that brought together laboratory and clinical scientists studying glaucoma and those studying other neurodegenerative diseases to explore common mechanisms of nerve cell damage and potential methods of protection.
RETINAL DISEASE RESEARCH
The retina is the transparent, light-sensitive tissue that lines the back of the eye. Diseases and disorders of the retina and its blood vessels account for much of the blindness and visual disability in this country. An important barrier to therapeutic intervention in human retinal disease is the identification of the gene or genes that cause vision loss. Visual loss and the degenerative and other changes in the retina are largely linked to rod and cone photoreceptors, the light-sensing nerve cells in the retina. Scientists have recently undertaken a comprehensive genetic analysis of rod photoreceptors, the most abundant sensory neuron in the retina, in order to identify all the possible genes expressed in these cells. Rod cells play an essential role in the visual pathway and may be especially vulnerable to any genetic defect involving the retina or other visual centers. For many identified retinal disease genes, a photoreceptor gene is mutated and its product is altered due to the mutation. Work is progressing on completing a database that will simplify the identification of candidate retinal disease genes, and many new genes in rod photoreceptors have already been identified.
Scientists have identified a mutation in a gene on the X chromosome that normally is associated with a form of retinitis pigmentosa (RP) that causes a progressive loss of rod photoreceptors in the peripheral retina and results in blindness in adulthood. This mutation was also reported to cause a unique type of degeneration in the macula, in a particular family. Further study may help us understand how this mutation specifically targets the macula and causes this unique loss of cones. This may lead to an understanding of the mechanisms of damage in other forms of macular degeneration and perhaps to the development of the means to prevent this type of damage to the macula.
The NEI is also funding studies on ocular albinism, a set of hypomelanotic diseases and conditions that are characterized by deficient cellular production of the pigment melanin. Deficiency in this pigment causes a cosmetic loss of ocular and skin pigmentation, but more importantly, it limits the development of vision in infants and children by fundamentally altering the connections between the eye and the brain. Recently the OA1 gene, which is associated with most cases of the disease, was identified. The form of the disease associated with OA1 is an X-linked or hereditary blinding eye disease that primarily affects boys at an early age. Although the cause or causes are unknown, misrouting of the neurons that go from the retina to the brain is involved. Understanding the causes of the abnormal neural cell axon guidance in ocular albinism may help us understand the fundamental neurobiology that underlies this disease and represents an important research initiative for the NEI.
CORNEAL DISEASE RESEARCH
NEI-supported scientists have also made progress against blinding diseases of the cornea. The cornea is the transparent tissue at the front of the eye that plays an important role in refracting or bending light to focus visual images sharply on the retina. Because the cornea is the most exposed surface of the eye, it is especially vulnerable to damage from injury or infection. One such infection is ocular onchocerciasis, commonly known as river blindness. Although river blindness is rare in developed countries, it is the second leading infectious cause of blindness in the world. This infection occurs when a nematode worm infects the cornea. Researchers have found that development and growth of the worm depends on a bacterium that lives within it. They found that the blindness associated with the infection was due to the reaction of the patient's immune system to the bacterium and not to the worm. The scientists discovered that an antibiotic that killed the bacterium also caused the death of the worm but without causing blindness. Further development of this treatment could revolutionize treatment of river blindness throughout the developing world.
Although cataract treatment in this country is one of the most successful of all surgical procedures, development of non-surgical approaches to preventing or treating cataracts remains an important area of research, because of the potential that it holds for reducing costs to the Medicare system and improving the quality of life of our senior citizens. A cataract is an opacity of the eye's normally clear lens that interferes with vision. Age-related cataract formation is believed to result from the complex effects of aging on normal physiological processes. Because the end-result, cataract formation, is in most cases far removed in time from the initial insult, exacting a cause and effect relationship has been difficult. Lens transparency results from the very high concentration of soluble proteins, the crystallins, within a specialized lens fiber cell. During aging and cataract formation, soluble lens crystallins tend to combine or aggregate into large complexes that cause light to scatter. NEI-sponsored researchers have found that alpha-crystallin, which normally protects the lens by binding to other proteins, may itself become the vehicle for the aggregate formation that accelerates cataract formation. Additional research in this area may provide the means for clinicians to intervene prior to the formation of a clinically evident cataract.
Other scientists are attempting to determine the genes that control one of the earliest events in the development of the eye, the development of the lens. Scientists studying lens development have identified a master gene that controls the expression of a number of other critical genes. Two of these critical genes that have recently been discovered. Without these two genes, the development of the lens is stopped and crystallin-synthesizing cells fail to form. These findings add to our understanding of the overall control of lens and eye development and may ultimately enhance our knowledge of the molecular basis of congenital diseases of the eye, thereby opening the possibility of future interventions.
STRABISMUS, AMBLYOPIA, AND VISUAL PROCESSING RESEARCH
The most frequent causes of vision loss in our children are strabismus, a misalignment of the eyes, and the development of amblyopia, or lazy eye. Strabismus results in diseases in which visual processing is abnormal. Amblyopia can result from this misalignment or from unequal refraction between the eyes. NEI-supported scientists have found that eye drops used to treat amblyopia work as well as the standard treatment of patching the eye. This research finding may lead to better compliance with treatment and improved quality of life in children with this eye disorder. Patients continue to be followed in this study to better assess the long term effects these treatments have on visual acuity.
Recent work by NEI-sponsored researchers has helped our understanding of nerve cell regeneration. Following injury or disease, neurons in the central nervous system (CNS) have a limited regenerative capacity, unlike nerve cells in the peripheral nervous system. Nerve cells typically have two types of extensions that arise from their cell bodies. Axons are normally quite long and extend over considerable distances. Dendrites are much shorter and extend short distances from the cell body. The inability of CNS neurons to regenerate is due to the failure of their axons to re-grow. These scientists found that axon growth may be due to a factor within the nerve cell itself rather than in the surrounding environment and may be regulated by signals from other nerve cells. Further research may allow discovery of the signals that switch neurons back to the axonal growth mode to repair damage to nerve tissue from injury or disease.
Scientists recently reported the prevalence of glaucoma in a population-based study conducted among 4774 Mexican American adults residing in two communities in Arizona. Glaucoma prevalence rates have been reported previously for white and African American adults, but no similar studies have been conducted among the U.S. Hispanic population. The prevalence of open-angle glaucoma in this Mexican American population was intermediate between the high rates reported for African Americans and the lower rates reported for whites. Of those diagnosed with glaucoma, only 38% were aware they had the disease. The prevalence of glaucoma increased rapidly with age and was the leading cause of bilateral blindness in this population. This information will allow health educators to create additional glaucoma awareness campaigns to increase awareness of the importance of glaucoma treatment in the Mexican American population, thereby allowing eye care providers to identify and treat those at greatest risk so that blindness can be prevented.
Diabetic retinopathy is a potentially blinding complication of diabetes characterized by the uncontrolled growth of fragile new blood vessels in the retina that may leak fluid and blood threatening vision. It is the leading cause of new cases of blindness in working age adults in the U.S. Macular edema secondary to diabetic retinopathy is also a major cause of visual loss in patients with diabetes. The NEI is developing a clinical research network of core centers and participating clinics that will help satisfy the need to evaluate promising new approaches to treat diabetes induced retinal disorders and to investigate other approaches as they become available. This network approach will provide a framework for rapid initiation of important studies, efficient use of pooled clinical expertise in idea generation and protocol development, and efficient use of central resources for data management, quality control, and endpoint evaluation.
The NEI is also planing to increase the pace of research in age-related macular degeneration (AMD) prevention and treatment by supporting a wide array of laboratory and clinical studies. AMD is the leading cause of severe vision loss in older persons in the United States, and it will have an increasingly important social and economic impact as the population ages. These studies may range from pilot work to the establishment and implementation of clinical research networks. It is anticipated that a network approach to AMD clinical research will hasten development of the more successful therapies for the treatment or prevention of AMD.
The NEI is also undertaking a major effort to reinvigorate the intramural research program and enhance resources to neurodegenerative and genetic forms of vision loss. Ocular genetics research has demonstrated that many common eye diseases have complex genetic and environmental etiologies that must be understood before innovative biological treatments can be designed. NEI is working on a new laboratory program devoted to complex human eye disease to hasten progress in this area.
Mr. Chairman that concludes my prepared statement. I would be pleased to respond to any questions you or other members of the committee may have.