This application is requested to further the career development of an academic pediatric ophthalmologist with a scientific interest in elucidating the response to intraocular surgery and discovery of novel therapies to prevent or treat postoperative complications in children and improve visual outcomes. The short-term goal is to develop the candidate's career as a clinician-scientist by expanding her understanding of ocular immunology and pathology and improve her research design, techniques and analysis skills. This will be achieved with mentorship, practical training, coursework, and involvement in a network of investigators. The environment at the University of Illinois is an ideal institution fo the candidate to transition to independence because of the available facilities, faculty, staff, an financial support. The priority of the Medical School and Department of Ophthalmology and Visual Sciences at the University of Illinois are to nurture early career clinician-scientists into independent investigators. They have demonstrated this commitment in the form of material, financial, technical, and administrative support for the candidate to achieve the goals of this proposal. There is a significant clinical need for the prevention and treatment of postoperative complications from exaggerated inflammation and fibrosis in children because of the risk of irreversible decreased vision from amblyopia. The objective of this proposal is to establish age-related changes in aqueous humor inflammatory mediators and determine the effect of pharmacologic intervention on inflammation and fibrosis after intraocular surgery. This will be accomplished with three specific aims:
Specific Aim 1. Establish differences in aqueous humor inflammatory mediators before and after intraocular surgery in children and adults. Intraocular fluid samples from subjects who are surgically nave and with a history of surgery will be analyzed with a Multiplex Bead-Based Immunoassay to simultaneously determine the levels of multiple inflammatory mediators. This will determine which proteins may be involved in the age-related response differences to intraocular surgery.
Specific Aim 2. Determine changes in inflammation and fibrosis before and after intraocular surgery with aging in a rabbit model. Lensectomy of juvenile, adolescent, and adult rabbits without postoperative treatment will be used as a model of age-related differences in response to intraocular surgery. Analysis of aqueous humor inflammatory protein levels and comprehensive evaluation of clarity of the visual axis, inflammation and fibrosis, intraocular pressure, and corneal thickness will be used to systematically evaluate the response to lensectomy as rabbit's age. This will determine how aging affects inflammation and fibrosis in a rabbit model of lensectomy.
Specific Aim 3. Determine the effect of intraocular pharmacologic intervention on inflammation and fibrosis in a juvenile rabbit model of lensectomy. Inflammatory mediator levels will be analyzed, along with standardized postoperative evaluation of clarity of the visual axis, inflammation and fibrosis, intraocular pressure, and corneal thickness. This will identify the most effective pharmacologic intervention for the prevention and treatment of postoperative inflammation and fibrosis following juvenile rabbit lensectomy. The findings from this proposal will serve as the scientific and technical foundation for future studies characterizing the response to intraocular surgery. These studies will identify novel age-related responses in eyes that may cause adverse outcomes after intraocular surgery in children. A clear understanding of the processes that result in complications from surgery will aid in the discovery of effective therapies. With effectie preventative and therapeutic interventions, we can have a lifelong impact by improving visual outcomes in children. The training, mentoring, and career development plan in this proposal will transition the candidate to an independent investigator making long-lasting contributions to the visual science community and vision care.

Public Health Relevance

In children, achieving the best vision after eye surgery, such as cataract surgery, is more difficult than adults because there is a higher risk of complications from scarring and inflammation. This proposal will establish how the immune response of the eye to surgery changes with age and determine the effects of certain medications on inflammation and fibrosis after surgery. The findings from this project will be the groundwork for future studies to understand the response to eye surgery and will enable us to identify and evaluate potential therapies to improve surgical outcomes in children.

National Institute of Health (NIH)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZEY1)
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Agarwal, Neeraj
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University of Illinois at Chicago
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United States
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