Mr. Chairman and Members of the Committee: I am pleased to present the President’s Budget request for the National Eye Institute (NEI) of the National Institutes of Health (NIH). The fiscal year (FY) 2015 budget proposal is $675,168,000, which is $0.9 million more than the FY 2014 Enacted level of $674,249,000. As the director of the NEI, it is my privilege to report on the many research opportunities that exist to reduce the burden of eye disease.
NEI AUDACIOUS GOAL INITIATIVE
Vision research is often on the cutting edge of biomedical research, from the first successful gene therapy clinical trials that restored some visual function in patients with an inherited form of blindness, to clinical trials for macular degeneration using tissue derived from embryonic stem cells, to a retinal electrical prosthesis, approved this past year by the FDA, after years of development by Second Sight, a small business that received research support from both NEI and the Department of Energy. NEI is now starting a new chapter in its ambitious research agenda. I have launched a new initiative—The NEI Audacious Goal Initiative in Vision Research and Blindness Rehabilitation—to identify a groundbreaking long-term research goal that will markedly improve prevention and treatment of common eye diseases.
We started this effort over a year ago by soliciting audacious ideas from scientists, stakeholders, patients, clinicians, and the public through a Challenge Competition. After a thorough scientific review of more than 500 submissions, we chose 10 winning entries, which were presented and intensively discussed at the NEI Audacious Goals Development Meeting last year. In May, I announced that the NEI Audacious Goal will be to Regenerate Neurons and Neural Connections in the Eye and Visual System. To kick start this initiative, we will soon release funding opportunities focusing on different components of this goal. Implementation of work toward the goal will include oversight, guidance, and direction from non-governmental consultant experts.
This goal will focus on two types of retinal neuronal cells that underpin many of the leading causes of visual impairment. One such target is photoreceptor cells, the specialized neurons in the retina that detect light and initiate the neural response. Blindness in some diseases, such as retinitis pigmentosa, is a direct result of photoreceptor cell death, whereas in other diseases such as diabetic retinopathy or macular degeneration, damage elsewhere in the retina indirectly causes photoreceptor cells to die.
Retinal ganglion cells (RGCs) are the second cell type targeted in this program. These neurons reside in the retina but send long projections (axons in the optic nerve) that connect to the brain. When RGCs degenerate and die in diseases such as glaucoma and multiple sclerosis, vision signals from the eye can’t get to the brain. Two of the primary scientific challenges of this initiative include protecting newly regenerated cells from dying, and inducing them to form appropriate neural connections in the brain. Success in achieving this goal will not just revolutionize how we approach diseases in vision, but all of neuroscience.
NEI is also a key contributor and participant in the President’s BRAIN initiative, which seeks to decode the brain, just as the Human Genome Initiative decoded DNA. While NEI’s Audacious Goal is independent from the BRAIN initiative, the eye is the gateway to the brain—it is the most accessible part of the central nervous system. There is good opportunity for synergy between these exciting initiatives.
NEW AREAS OF EMPHASIS
In the process of identifying our Audacious Goal, we also identified two high-priority, complementary areas of emphasis, for which we have released two funding opportunities and are currently reviewing grant applications: Molecular Therapy for Eye Disease; and the Intersection of Aging and Biological Mechanisms of Eye Disease. With recent advances in genomics, we now have a good understanding of genes and molecules that are altered in many diseases. The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE), is a critical resource created by NEI for identifying the mutated genes in patients with inherited eye disorders and giving researchers access to DNA samples (over 4,000 collected since 2006), clinical information, and patients looking to participate in research studies. But the current tools at our disposal to treat genetic diseases are limited. Building on our recent successes in gene therapy, the exciting potential of designing personalized therapies to correct mutant genes lies in the research ahead of us over the next decade.
Many eye diseases are associated with aging: from cataracts and presbyopia, which are common in all adults as they age, to some of the leading vision impairment diseases, age-related macular degeneration (AMD) and glaucoma. Understanding what aspects of the aging process contribute to eye disease has the potential to delay the onset of vision loss or even avert the disease.
NEI REGENERATIVE MEDICINE PROGRAM
Also contributing to the Audacious Goal Initiative are researchers at NEI, working with the NIH Center for Regenerative Medicine to create retinal tissues from induced pluripotent stem (iPS) cells for several basic and translational research applications. iPS cells can be generated from any adult cell, and then converted into virtually any other type of cells. A major thrust of this program is to derive iPS cells from patients with retinal diseases. Then, the iPS cells are differentiated to form retinal pigment epithelial (RPE) cells or photoreceptors and studied to identify disease-causing molecular pathways. Diseases of interest currently include AMD, Best disease, late-onset retinal degeneration, Stargardt's disease, and retinitis pigmentosa. This program is exploiting these techniques to develop high-throughput drug screens to identify potential therapeutic compounds for treating retinal degenerative diseases.
Another potentially powerful application of iPS cell technology is to generate iPS cells from normal tissue and then differentiate those cells into monolayer sheets of RPE for tissue transplants. NEI intramural investigators are engineering a bio-degradable scaffold in order to grow the RPE tissue and transfer it to patients with RPE-associated retinal degenerative diseases. In FY 2015, the stem cell program will also use stem cell technologies to evaluate synaptic connections in 3-D retinas derived from iPS cells.
As I reflect on the remarkable progress the vision community has made in these past few years, I can hardly anticipate the exciting opportunities that lay ahead.