Regulation of neural stem cells in retina regeneration

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DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) and diabetic retinopathy are diseases that lead to deterioration of the neural retina and two major causes of blindness in those over 65. Regeneration of retinal tissue may be a possible treatment for vision loss that would greatly improve the quality of life for many elderly individuals. The developing chick has the ability to regenerate a complete neural retina in response to injury from a population of neural retina stem/progenitor cells present in the anterior margin of the eye. Two secreted proteins, Wnt and BMP, have been shown to activate signaling pathways important for proliferation, differentiation and maintenance of neural stem/progenitor cells of the retina, brain, and spinal cord. Molecules from both of these pathways are expressed in the anterior margin of the chick eye during development and may therefore play a role in the regulating the neural retina stem/progenitor cells present in this region. Studies in Aim 1 are designed to determine the expression pattern of key molecules in the Wnt and BMP signaling pathways during retina regeneration in the embryonic chick via in situ hybridization, RTPCR, immunohistochemistry and Western blotting. Aim 2 is designed to determine the role the Wnt and BMP signaling pathways play in regulating neural retina stem/progenitor cells during retina regeneration by either activating or inhibiting such pathways using retroviral vectors after retinal damage is induced in the developing chick eye. Aim 3 is designed to use the information obtained from specific aims 1 and 2 to induce or increase the activation of neural retina progenitor/stem cells found in more mature eyes which would normally lack or have a reduced ability to regenerate. The results of this study will greatly enhance the field of neural regenerative biology and may lead to new therapeutic drugs or treatment for AMD and diabetic retinopathy as well as other neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.