title: Novel usage of intraocular pressure-lowering drugs as wound-healing inhibitors after trabeculectomy with cell culture and animal models.
abstract: Inhibiting the healing of wounds to ensure that the aqueous humor can drain into the scleral space unimpeded and form a filtering bleb plays a crucial role in determining the success rate of glaucoma surgery. The aim of this study was to investigate the novel use, with cell culture and animal models, of some commercial intraocular pressure (IOP)-lowering drugs in inhibiting the healing of fibroblast wounds. The Tenon's fibroblasts of rabbits were cultured to evaluate 13 IOP-lowering drugs for cellular proliferation, collagen formation, and migration. These were measured using [(3)H]thymidine and [(3)H]proline uptake, and Transwell chambers. A preservative of benzalkonium chloride (BAK) was initially used, with 0.02% as a maximal original concentration. All of the drugs and the BAK were diluted from original commercial concentrations to 1/10, 1/100, and 1/1000. The more inhibitive drugs screened from the cell cultures were then selected for further short-term application during and after trabeculectomy surgeries had been performed on the rabbits. Expression of the proliferative cell nuclear antigen was immunohistochemically examined 3 and 7 days after surgery. The results revealed that the inhibitive effects of BAK in cellular [(3)H]thymidine and [(3)H]proline uptake, and cellular migration were only evident at 0.002% concentrations. Based on the results of the cell cultures, timolol, latanoprost, and unoprostone exhibited a greater inhibitory effect than the other drugs. Moreover, the animal studies showed that latanoprost and unoprostone significantly suppressed the positive expression of proliferative cell nuclear antigen around the operative excision area 7 days after the trabeculectomy surgeries. The results indicate that short-term use of some IOP-lowering drugs, such as latanoprost and unoprostone, may inhibit postoperative wound healing after glaucoma surgery.
authors.affiliation: Department of Ophthalmology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors.forename: Kwou-Yeung
authors.initials: KY
authors.lastname: Wu
authors.forename: Pei-Cheng
authors.initials: PC
authors.lastname: Wu
authors.forename: Yu-Hung
authors.initials: YH
authors.lastname: Lai
authors.forename: Show-Jen
authors.initials: SJ
authors.lastname: Hong
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D001548:Benzalkonium Compounds / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007429:Intraocular Pressure; D000077338:Latanoprost; D009883:Ophthalmic Solutions; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D013999:Timolol / Q000494:pharmacology*; D014130:Trabeculectomy; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001548:Benzalkonium Compounds; D015415:Biomarkers; D009883:Ophthalmic Solutions; D018809:Proliferating Cell Nuclear Antigen; D011461:Prostaglandins F, Synthetic; C072630:isopropyl unoprostone; D000077338:Latanoprost; D013999:Timolol; D003094:Collagen; D015237:Dinoprost