NEI requests budget increase to expand research in FY2008

For fiscal year 2008, the president’s budget request includes $667.8 million to the National Eye Institute, a $1.5 million increase over the 2007 continuing resolution level. These funds will support research in: retinal diseases, corneal diseases, cataract, glaucoma, sensorimotor disorders and rehabilitation, intramural research and research management and support.

This budget will allow NEI investigators to continue work in understanding and treating common retinal disorders such as age-related macular degeneration (AMD) and diabetic retinopathy. The estimated budget to fund retinal disease research is $263.3 million.

“In 2008, the NEI will re-invigorate its intramural program to increase ophthalmic genetics research to further elucidate retinal diseases,” Paul A. Sieving, MD, PhD, NEI director, wrote in his overview of the congressional justification. To achieve this goal, the organization will hire several new principal investigators.

The Age-Related Eye Disease Study (AREDS), multicenter study of cataract and AMD, has shown that high-dose antioxidant supplements slow AMD progression. During fiscal year 2008, the NEI will expand AREDS 2, a multicenter, randomized, controlled clinical trial on oral supplementation with lutein/zeaxanthin and omega-3 long chain polyunsaturated fatty acids for preventing advanced AMD and cataracts. Recruitment is underway. Investigators will follow patients for 5 years, according to the overview.

Retinal research

“FY2008 expansion of the extramural program will investigate the role of inflammation in degenerative eye diseases, such as AMD, uveitis and other chronic disorders,” Dr. Sieving said. “Expansion will include the latest knowledge of the molecular and cellular aspects of inflammation, study development and progress of degenerative eye diseases.”

The primary cause of blindness in Americans is diabetic retinopathy. To help address this problem, the NEI has developed the Diabetic Retinopathy Clinical Research Network, a cooperative research group that includes clinicians from academic and private practice, he wrote. In 2008, this group will continue to expand its activities as several promising investigational therapies are poised to enter clinical trials.

Research on the genetic and environmental basis for AMD will accelerate. It will include expansion of genome-wide association studies and related efforts in bioinformatics.

“There are now four or five AMD genes known,” Dr. Sieving told Primary Care Optometry News.

NEI will support projects that address possible vision restoration in retinal degenerative transplantation. They will include precursor cell biology, bone marrow stem cell transplantation and “re-engineering” the production of light-sensitive proteins in retinal neurons.

The NEI and the National Heart, Lung and Blood Institute will continue to collaborate on the ocular component of the Multi-Ethnic Study of Atherosclerosis (MESA), which is examining ways to control angiogenesis in several eye diseases. The investigators are trying to determine which factors predict symptom development and progression to overt cardiovascular disease in different ethnic groups in diverse geographical locations, according to the justification.

Cornea, cataract, glaucoma

The NEI will continue to focus many research efforts on corneal diseases, cataract and glaucoma because of their prevalence, Dr. Sieving wrote. The estimated budget for this work is $164.4 million.

In 2008, investigators will study corneal biology, particularly as it relates to tear film, eyelids, conjunctiva and other ocular tissues, he wrote. In addition, they will examine how the cornea encourages wound healing while remaining transparent. They will also study the molecular causes of cornea dystrophies. “The science of molecular etiologies is among the hardest to identify,” Dr. Sieving told Primary Care Optometry News.

According to current estimates, 27 million Americans older than 40 have cataract or have had surgery to remove cataract. By the year 2020, researchers estimate that about 40 million Americans will be affected by cataract.

“NEI cataract research seeks to understand both the physiological basis of lens transparency at the cellular and molecular levels and seeks strategies to prevent cataract formation and prevention,” Dr. Sieving wrote.

For example, evidence suggests that nutrients moving through gap junctions, the small channels between cells in the lens, are critical to lens epithelial cell function. “Projects will be funded to examine the possible contribution of defects in the gap junction in the development of cataracts,” he wrote. 

By 2020, glaucoma prevalence is projected to rise from approximately 2.2 million diagnosed Americans to 3 million.

“Glaucoma research aims to understand complex genetic factors leading to common forms and develop treatments that protect ganglion cells from the damage that leads to vision loss,” Dr. Sieving wrote.

Role of genes, environment

With the launch of genome-wide association studies and related bioinformatics efforts in 2008, NEI researchers will examine how genetics and environment affect glaucoma development. They will also try to gain a better understanding of patients’ response to medications, according to Dr. Sieving. In addition, they will follow up on an animal model finding that the immunologic destruction of certain cells that normally surround the optic nerve may kill retinal ganglion cells.

The NEI will increase its participation in the Age Gene/Environment Susceptibility Study with the National Institute on Aging and other institutes. The NEI will fund the ocular arm of the study, which is examining the contributions of candidate genes and the environment in diseases that are common in old age, Dr. Sieving wrote.

The NEI’s sensorimotor research goals are twofold: develop a better understanding of visual system development in children at high risk for strabismus and amblyopia and understand neural circuitry and muscular mechanisms that control gaze. The 2008 budget estimate in this area is $142.1 million.

Research goals include studying the genes involved in Leber’s hereditary optic neuropathy and examining how the activity of certain brain cells permits a stable view of the surroundings despite constant head/eye movements.

“This research will help us to understand better the neural control of eye movements and associated disorders and may have applicability in other sensory systems,” Dr. Sieving wrote in the justification.

Refractive errors, such as myopia, hyperopia and astigmatism are the most common correctable visual disorders. In 2008, NEI researchers will work to identify biochemical pathways that govern much eye growth and to discover risk factors associated with refractive errors.

 The priorities of the NEI’s visual processing portfolio include understanding:

• how the brain processes visual information,
• how neural activity is related to visual perception and
• how the visual system interacts with other cognitive systems.

Chronic visual conditions not correctable with eyeglasses or contact lenses affect 3 million Americans.

“The NEI supports visual impairment rehabilitation research on improving the quality of life by helping patients maximize their remaining vision and by devising improved aids to assist those without useful vision,” Dr. Sieving wrote.

Intramural research

The NEI’s budget estimate for intramural research is $66.5 million. Researchers at the NIH’s Bethesda, Md., campus and in Rockville, Md., will continue to conduct investigations into the major causes of blindness, Dr. Sieving stated. According to the overview, their work will focus on the following:

• cellular and molecular mechanisms of eye development, including gene expression and function within the eye
• immunology and infectious diseases to better grasp the normal physiological state and the processes that affect it, emphasizing inflammatory mechanisms in the eye as a model system
• developing a better understanding of fundamental brain mechanisms that allow the eye to guide movements under neurosensory control

During 2008, the NEI will close several research sections and one laboratory because of a change in program emphasis, Dr. Sieving wrote. Work is underway, however, to launch or expand several new research activities.

Part of this plan involves developing a retinal neurodegeneration research program that will accelerate the introduction of therapeutic interventions in various eye diseases. The interventions include: gene therapy, small molecules, neurotrophic factors and cell-based systems, in combination with various treatment delivery technologies. Development of clinical neuroscience research capabilities within the Laboratory of Sensorimotor Research will build on a very strong experimental and theoretical analysis of normal and abnormal eye movements and visual perception.

The $22.7 million for research management and support funds will be used to sustain and maintain extramural and intramural research programs.

Elias Zerhouni, MD, National Institutes of Health director, offered his support of the budget justification during the committee hearing.

“We believe we are on the path to transforming medicine from the current practice of intervening often too late in a disease to a new era when medicine will be more predictive, personalized and preemptive, through broader scientific understanding of the fundamental mechanisms that lead to disease years before it strikes the patient.”

For more information:

• Paul A. Sieving, MD, PhD, can be reached at the Office of the Director, National Eye Institute, 31 Center Dr. MSC 2501, Bldg. 31, Rm. 6A03, Bethesda, MD 20892-2510; (301) 496-2234; fax: (301)496-9970; e-mail: pas@nei.nih.gov.
• Barbara Anan Kogan, OD, can be reached at 4501 Connecticut Ave. NW, Ste. 102, Washington, DC 20008-3711; phone/fax: (202) 244-1324; e-mail: bakogan@mindspring.com.
• Access information on the National Institutes of Health’s National Eye Health Education Program (NEHEP) at www.nei.nih.gov/nehep/ and the National Eye Institute’s National Ophthalmic Disease Genotyping Network (eyeGENE) at http://www.nei.nih.gov/resources/eyegene.asp.

Suggested reading:

• The Eye Diseases Prevalence Group. Prevalence of cataract and pseudophakia/aphakia among adults in the United States. Arch Ophthalmol. 2004;122:4876-4494.
• The Eye Diseases Prevalence Group. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122:512-538.
• Sieving PA, Collins FS. Genetic ophthalmology and the era of clinical care. JAMA. 2007;297(7):733-736.