The precise effects of laser trabeculoplasty (LTP) on the trabecular meshwork remains only partially understood. Its intraocular pressure-lowering effect through enhancement of aqueous outflow is well documented. Clinically, this effect seems relatively non-specific for laser characteristics. The response 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 of 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 in human cornealscleral explant organ culture. This division is localized primarily to a population of anterior trabecular cells, which reside beneath 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 initiated 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 metalloproteinases which initiate extracellular matrix turnover and remodeling, and this cascarde 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 between these observations and aqueous outflow, as monitored by fluorophotometry antonometry, 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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008247-03
Application #
3265474
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Vranka, Janice A; Staverosky, Julia A; Reddy, Ashok P et al. (2018) Biomechanical Rigidity and Quantitative Proteomics Analysis of Segmental Regions of the Trabecular Meshwork at Physiologic and Elevated Pressures. Invest Ophthalmol Vis Sci 59:246-259
Raghunathan, Vijay Krishna; Benoit, Julia; Kasetti, Ramesh et al. (2018) Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior. Acta Biomater 71:444-459
Vranka, Janice A; Acott, Ted S (2017) Pressure-induced expression changes in segmental flow regions of the human trabecular meshwork. Exp Eye Res 158:67-72
Dang, Yalong; Loewen, Ralitsa; Parikh, Hardik A et al. (2017) Gene transfer to the outflow tract. Exp Eye Res 158:73-84
Yang, Yong-Feng; Sun, Ying Ying; Acott, Ted S et al. (2016) Effects of induction and inhibition of matrix cross-linking on remodeling of the aqueous outflow resistance by ocular trabecular meshwork cells. Sci Rep 6:30505
Vranka, Janice A; Bradley, John M; Yang, Yong-Feng et al. (2015) Mapping molecular differences and extracellular matrix gene expression in segmental outflow pathways of the human ocular trabecular meshwork. PLoS One 10:e0122483
Vranka, Janice A; Kelley, Mary J; Acott, Ted S et al. (2015) Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma. Exp Eye Res 133:112-25
Abu-Hassan, Diala W; Li, Xinbo; Ryan, Eileen I et al. (2015) Induced pluripotent stem cells restore function in a human cell loss model of open-angle glaucoma. Stem Cells 33:751-61
Keller, Kate E; Yang, Yong-Feng; Sun, Ying Ying et al. (2014) Interleukin-20 receptor expression in the trabecular meshwork and its implication in glaucoma. J Ocul Pharmacol Ther 30:267-76
Acott, Ted S; Kelley, Mary J; Keller, Kate E et al. (2014) Intraocular pressure homeostasis: maintaining balance in a high-pressure environment. J Ocul Pharmacol Ther 30:94-101

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