MECHANISM OF ACTION

The adrenal medullary hormone, epinephrine, is the

systemic analog of the neurotransmitter, norepinephrine
(Figure 321A). These are nonselective agonists for all the
subtypes of both alpha- and beta-adrenergic receptors.
Studies indicate that epinephrine stimulates the beta-receptor
of the ciliary body,5 producing an early increase in aqueous
flow. However, the predominant effect of epinephrine
results from alpha2-receptor-mediated vasoconstriction in

the ciliary body, which decreases aqueous production. In

addition, experimental models have implicated an increase
in outflow facility, both via beta-receptors in the trabecular
meshwork and via the uveoscleral pathway.69 The mechanisms
of this increased outflow facility may be mediated
through increased intracameral levels of cyclic adenosine
monophosphate (cAMP).10

Steroid-induced alterations in the TM cytoskeleton

may lead to decreased proliferation,41,43 migration,41 and
phagocytosis43,44 of TM cells. Reduced proliferation and
migration likely produce the diminished cellularity seen in
the TM of patients with steroid-induced glaucoma.
Because these cells are normally highly phagocytic and
provide a self-cleaning filter function to the TM, inhibition
of phagocytosis may lead to progressive accumulation
of extracellular debris, a clogging of the meshwork,
and increased aqueous outflow resistance.45
Steroids can also alter gap junctions (protein complexes
that couple TM cells together) and mediate cell-to-cell communication.
In addition, steroids may tighten connections
between cells and increase aqueous outflow resistance.46
Glucocorticoids also can change the expression of several
TM cell integrins,35,36 which are ECM receptors found in the
cell membrane linked to the actin cytoskeleton, further
affecting TM cell function and migration.