The primary objective of this project is to develop new methods for controlling wound healing following glaucoma filtration surgery (GFS) through the technology of polymeric delivery- controlled drug delivery. Bioerodible polymers will be used fot the localized and sustained of various drugs which inhibit scar tissue formation at the site of GFS in an animal model. A series of prospective, randomized, double-masked, and placebo- controlled experiments in an animal model will be performed by comparing a bioerodible polymer impregnated with a certain drug or drug combination to the same bioerodible polymer without any drug. All animals will undergo preoperative eye examinations including slit lamp biomicroscopy and pneumotonomery. A standard posterior lip sclerectomy will be performed on both eyes of each animal under general anesthesia. The polymer with drug will be randomly implanted in one eye and the fellow eye will receive the placebo polymer. Eye examinations will be performed one day after surgery and every other day thereafter for a minimum of five weeks or until the filtering surgery in the experimental eye fails. The parameters measured will include intraocular pressure, outflow facility, the appearance of the bleb, conjunctiva, polymer implant, cornea, and anterior chamber. At various times following surgery, histopathological examination will be performed on both experimental and control eyes. Quantitative morphology and immunohistochemistry will be used to assess the effect of drug delivery on scarring. This study will develop and refine the polymer characteristics of composition, dissolution rate, drug release rate, geometrical shape, and possible lamination with different drugs in order to improve its efficacy in GFS. An in vitro tissue culture system of fibroblasts will be developed to screen potentially useful drugs for delivery by the bioerodible polymers and to study the drug release characteristics of the bioerodible polymers impregnated with drugs. The in vitro fibroblastic growth will be measured by direct counting of fibroblasts and by using methyl-14C thymidine uptake. Using bioerodible polymers as a drug delivery device in GFS may dramatically improve the success of this procedure in patients at high risk for failure.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007701-03
Application #
3264709
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1988-08-01
Project End
1991-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Rabowsky, J H; Dukes, A J; Lee, D A (1997) Gonioscopic laser sclerostomy versus filtration surgery in a rabbit model. Eye (Lond) 11 ( Pt 6):830-7
Rabowsky, J H; Dukes, A J; Lee, D A et al. (1996) The use of bioerodible polymers and daunorubicin in glaucoma filtration surgery. Ophthalmology 103:800-7
Cheng, Q; Shapourifar-Tehrani, S; Lee, D A (1995) Comparative efficacy of antiviral drugs on human ocular fibroblasts. Exp Eye Res 61:461-7
Choi, T B; Lee, D A; Oelrich, F O et al. (1995) A retrospective study of eye disease among first grade children in Los Angeles. J Am Optom Assoc 66:484-8
Smyth, R J; Kitada, S; Lee, D A (1994) Growth of rabbit pigmented and nonpigmented ciliary body epithelium. Vision Res 34:137-41
Uppal, P; Jampel, H D; Quigley, H A et al. (1994) Pharmacokinetics of etoposide delivery by a bioerodible drug carrier implanted at glaucoma surgery. J Ocul Pharmacol 10:471-9
Ahn, S S; Williams, D E; Thye, D A et al. (1994) The isolation of a fibroblast growth inhibitor associated with perigraft seroma. J Vasc Surg 20:202-8
Givens, K T; Lee, D A; Jones, T et al. (1993) Congenital rubella syndrome: ophthalmic manifestations and associated systemic disorders. Br J Ophthalmol 77:358-63
Sarraf, D; Lee, D A (1993) Iontophoresis of reactive black 5 for pulsed dye laser sclerostomy. J Ocul Pharmacol 9:25-33
Sarraf, D; Equi, R A; Holland, G N et al. (1993) Transscleral iontophoresis of foscarnet. Am J Ophthalmol 115:748-54

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