|Ph.D Student||Michael Inbal|
|Subject||Mechanisms of Infantile Aphakic Glaucoma|
|Department||Department of Biomedical Engineering||Supervisor||Professor Shulamit Levenberg|
|Full Thesis text|
Infantile aphakic glaucoma may develop as a postoperative complication of congenital cataract surgery. It has been associated with risk factors including surgery in early life and retained lens material; however, its cause and mechanism are poorly understood. This study focused on the potential role of retained lens epithelial cells (LECs) in undesired changes of the trabecular meshwork (TM) structure and function. Using a LEC-TM co-culture model, we demonstrated alteration of TM cell morphology (increase in volume and size), protein expression (mainly cytoskeletal), and gene expression (such as genes related to inflammatory response and several signaling pathways) upon exposure to LECs. Many of these changes resemble alternations seen in primary open angle glaucoma. This strengthened the suspected role of LECs in the development of aphakic glaucoma, and led us to identify the factors secreted by the LECs responsible for the altered TM cells and to compare their effect on monocultured TM cells with that of TM cells co-cultured with LECs. TGFβ2, IL-4, and VEGF were found as candidate cytokines responsible for the observed changes in LEC-TM co-cultures. Culturing TM cells in the presence of VEGF and IL-4 triggered alterations closely reflecting those observed in the LEC-TM co-culture model, where their inhibition (by means of addition of specific antibodies to the cell culture media) significantly hindered the alteration of the TM cells. These findings suggest a possible explanation for the development of infantile aphakic glaucoma, based on residual IL-4 and VEGF-secreting LECs after removal of congenital cataract, which then alter TM cell morphology and gene expression.
Apparently, such interactions between LECs and TM cells could also occur after cataract removal in adults; this led us to assume young cells interact differntly than adult cells. Compared to adult TM cells, exposure of infant cells to infant LECs seemed to affect them more, and revealed possible additional mechanism of cell apoptosis, which should further be examined.