Framework for Vision Research (DRAFT)

January 2011

NOTE: This DRAFT document will be provided to all program planning panels as a reference to help the panel members focus on the needs and opportunities of their specific programs rather than the global concepts described in this framework. The NEI also requests input to this document as part of the Request for Input to the NEI Plan, Vision Research in 2011: Needs, Gaps, and Opportunities.

Biomedical research is a highly specialized endeavor. At its core are fundamental, overarching goals that drive the pursuit to understand, treat and prevent ocular disease. A deep knowledge of the underlying biology of vision is critical to understand and treat the pathological mechanisms of visual disorders and diseases. This document provides a framework for considering these fundamental properties and goals in the context of eye and vision research.

Goal 1: Gather comprehensive knowledge of the molecular basis of ocular health and disease, and use that knowledge to improve diagnosis, treatment, and prevention of eye disease

1.1. Develop a detailed, comprehensive understanding of the molecular, cellular, and physiological mechanisms that promote and maintain ocular health.

1.2. Identify key signaling and transcriptional pathways in normal and pathological states.

1.3. Determine key genetic and epigenetic variants that prevent or cause Mendelian as well as complex ocular diseases.

1.4. Characterize the changes in molecular processes affected by nutritional, behavioral and other environmental factors that impact ocular health and disease.

1.5. Understand the regulation of cellular oxidation, energetics and mitochondrial function in maintaining healthy ocular tissues.

1.6. Develop a better understanding of protein-protein interactions, regulation of protein folding, and diseases that result from mis-folded proteins.

1.7. Develop the ability to specifically modulate molecular pathways, systems, and intracellular complexes to treat and cure ocular injury and disease.

1.8. Develop tools (e.g. genomic markers, gene and/or protein expression profiles, and other new measurable indicators) to assess an individual's risk for particular ocular disorders.

Goal 2: Understand the effect of biological systems on visual function

2.1. Determine the role of inflammation, immunity, infection, blood pressure, circadian rhythms, and other systemic processes in complex eye diseases.

2.2. Understand the integration of structural, vascular, and neural processes that constitute the unique physiology of the ocular system.

2.3. Understand visual processing in normal and pathological states.

2.4. Characterize the developmental stages of the visual system from its precursor cells.

2.5. Gain a deep understanding of the physiology of aging. Understand the contribution of the aging process to adult onset disease.

2.6. Develop models to understand cellular pathways, systems, and interactions of systems in healthy and pathological ocular tissues.

Goal 3: Accelerate the translation of basic research into clinical studies

3.1. Develop, refine, and set standards for new technologies (e.g., molecular imaging, telemedicine, small molecules) for clinical research and clinical trial application.

3.2. Develop and validate biomarkers that are useful in diagnosing and stratifying patients, measuring disease progression and gauging therapeutic outcomes.

3.3. Foster multi-disciplinary teams to develop new ocular diagnostic and therapeutic approaches (e.g., nanotechnology, prosthetics, cell based therapies, molecular engineering and synthetic biology).

3.4. Develop appropriate animal models and cell cultures to study disease mechanisms and evaluate investigational therapies.

3.5. Develop and evaluate assays and high-throughput screens to further vision research and clinical application.

3.6. Improve gene delivery techniques that yield precise targeting and regulation of gene expression.

3.7. Integrate advances in regenerative medicine and tailor them to develop clinical applications in specific ocular tissues.

3.8 Develop new targeted therapies and combine them as appropriate to maximize treatment response.

3.9. Make research tools widely available, including easy access to novel compounds, reagents, animal models, cell lines, etc.

3.10. Infrastructure and strategies for collection and rapid dissemination of genomic, proteomic, and other molecular library data to the vision research community are needed.

Goal 4: Use clinical, epidemiologic, and statistical tools to identify at-risk populations and to evaluate new therapeutics

4.1. Develop strategies and/or infrastructure to foster early, well-designed pilot clinical trials to rapidly assess the potential of translational therapies or candidate predictive markers.

4.2. Conduct clinical trials for improved prevention and treatment strategies for ocular diseases and disorders.

4.3. Improve the understanding of the burden of eye diseases and their visual outcomes at the societal and individual level through epidemiological and social sciences research. Identify population disparities and use these data to inform and enhance translational and clinical trials.

4.4. Develop and apply new methodologies for epidemiological research and strategies for screening and detection of visual disorders.

4.5. Apply epidemiologic methods and clinical trial interventions to blinding global eye diseases.

Goal 5: Strengthen Clinical Research of Visual Disorders

5.1. Utilize developments in biotechnology and genomics to prioritize the testing of important molecular targets.

5.2. Develop new disease classification schemes and predictive models that incorporate genetic and molecular profiling.

5.3. Develop strategies and infrastructure to enable and encourage patients with ocular conditions to participate in clinical trials with special emphasis on recruiting minority populations.

5.4. Develop improved methods of clinical trial design that provide the capacity to evaluate therapeutic agents among patient subpopulations.

5.5. Develop strategies to improve efficiency in the clinical research enterprise such as common data elements, harmonized electronic data-capture systems, standardized training, and coordinated specimen management.

5.6. Complement bench discoveries and clinical trial results with focused behavioral and social science research, particularly in low-vision populations.

5.7. Integrate molecular and cellular knowledge with epidemiological and clinical information to inform clinical research priorities.

5.8. Promote the development and implementation of evidence-based guidelines for prevention, diagnosis, and treatment of visual disorders by conducting comparative effectiveness research.

Goal 6: Strengthen the Pool of Vision Researchers

6.1. Increase recruitment of clinician-scientists to vision research.

6.2. Encourage early stage vision researchers to participate in team science. Develop multidisciplinary teams with expertise in fields such as bioinformatics, nanotechnology, engineering, and physics.

6.3. Increase the participation of minorities in vision research.

6.4. Recruit early stage investigators from other disciplines to apply their knowledge and techniques to study disorders of the visual system.