DESCRIPTION (provided by applicant): Our long-term goal is to develop a comprehensive informatics-based approach to understand how pathological change in cell interactions promotes disease. To apply an advanced informatics to the research of retinal pathologies we developed efficient methods of purification and signature profiling primary neurons and glia, two closely interacting cell types in the retina. In this R21 project, we will test the feasibility of our approach using retinal cells derived from the eyes with elevated intraocular pressure, a mouse model of glaucoma. It is established that in the retina exposed to the elevated intraocular pressure a dramatic dysregulation in the vital glia-neuronal interaction promotes death of retinal neurons (RGCs), the cause of blindness in glaucoma. We will initiate glaucoma in the mice with genetically altered glial cells to study molecular interactions facilitating an increased survival of the RGCs in these animals. Informatics software tools will help converting an overwhelming amount of molecular data into concise hypothesis, visualized as graphical networks depicting the affected "parts" of cellular machinery. The results of this study will establish feasibility of our informatics-based approach to study pathogenic cell interactions in the retina. The results will provide candidate pathways for a therapeutical strategy targeting glial cells in glaucoma. This project develops novel molecular and bioinformatics strategies to address clinically important question of how the glial cells impact retinal ganglion cell survival in glaucoma. Although glial activation is detrimental to the homeostasis of the retina, methods to analyze and restore such imbalances remain currently undeveloped. The methodology that will be tested here and the results that will be obtained in this feasibility study can be utilized to search for and test new potential therapeutic targets for glaucoma.
|Effective start/end date||9/30/07 → 8/31/09|
- National Institutes of Health: $187,425.00
- National Institutes of Health: $213,865.00
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