Mechanisms of Abnormal Angiogenesis in Retinal Disease

Abnormal angiogenesis is often the final step towards loss of vision in many retinal diseases, including exudative age-related macular degeneration. While many risk factors have been found to be linked to elevated levels of angiogenic proteins in the eye, the exact mechanisms leading to abnormal angiogenesis remain unclear. Loss of cell-cell contact and mechanical stress are two understudied phenomena that are often associated with retinal degeneration. The hypothesis of this work is that mechanical stress and loss of cell-cell contact can promote initiation and/or progression of aberrant angiogenesis in the retina by inducing the expression of angiogenic proteins. To test this hypothesis, we used novel engineering methods, such as micropatterning, to investigate the role of intercellular junctions and mechanical stress in regulating the expression of a potent angiogenic protein, vascular endothelial growth factor (VEGF). Our results suggest that both of these phenomena can induce VEGF expression in retinal pigment epithelial (RPE) cells, a cell layer that supports the photoreceptors and maintains retinal function. In an ongoing work, we are developing a realistic model of the subretinal tissue to further study the role of cell- cell contact loss and mechanical stress in regulating angiogenic protein expression in the RPE and to determine whether these changes can lead to abnormal angiogenesis