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.
