The precise effects of laser trabeculoplasty (LTP) on the trabecular meshwo k remains only partially understood. Its intraocular pressure-lowering effec through enhancement of aqueous outflow is well documented. Clinically, thi effect seems relatively non-specific for laser characteristics. The respon e is delayed in onset, diminishes over time, and in some cases can be renewed with retreatment. Viewed histologically, the acute effects of LTP are regional trabecular beam and cellular destruction; repopulation of the burn sites is documented. The objective of this research project is to unravel the cellular biology o the events that result in this repopulation and the subsequent increase in aqueous outflow facility. Preliminary studies show a transient, early (48 hours) induction of trabecular cell division in response to LTP treatment i human cornealscleral explant organ culture. This division is localized primarily to a population of anterior trabecular cells, which reside beneat Schwalbe's line at the insert of the meshwork into the corneal. By 7 to 14 days post-treatment, the cells which divided early are found predominantly in the site of repopulation of the burn. These events appear to be initiat d by a cellular modulator, which is released from the meshwork within 8 hours following LTP. In this application, cell biological, biochemical and some molecular biological methodologies are proposed as a means to investigate this early cellular division, the cellular migration which repopulates the burn sites, and the regulatory factors which modulate these events. Evaluation of the relationship between the production of a family of matrix metalloproteinase , which initiate extracellular matrix turnover and remodeling, and this casca e of cellular trabecular responses is proposed. In other studies, these results are extended to a feline in vivo model to establish the relationship between the in vitro and the in vivo models' responses to LTP. The specificity of the effect on trabecular cells of a number of select LTP treatment parameters is evaluated. Correlations betwe n these observations and aqueous outflow, as monitored by fluorophotometry an tonometry, are then evaluated. These studies will provide important information about trabecular biology, as well as about the mechanism of action of LTP upon the trabecular meshwork.
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