title: Tissue plasminogen activator in trabecular meshwork attenuates steroid induced outflow resistance in mice.
abstract: Tissue plasminogen activator, a serine protease encoded by the PLAT gene is present in the trabecular meshwork (TM) and other ocular tissues and has been reported to be downregulated by treatment with steroids in vitro. Steroids are known to cause changes in outflow facility of aqueous humor in many species. In the present study, we tested whether overexpression of PLAT can prevent and/or reverse the outflow facility of mouse eyes treated with steroids. Animals received bilateral injection with 20 µl of triamcinolone acetonide (TA) (40 mg/ml) suspension subconjunctivally to induce outflow facility changes. Some animals received unilateral intracameral injection with 2 µl of adenoviral suspension [3-4 x 10(12) virus genomes per milliliter (vg/ml)] carrying sheep PLAT cDNA (AdPLAT) either concurrently with TA injection or one week after TA injection, whereas others received bilateral intracameral injection with 2 µl of adenoviral suspension (9 x 10(12) vg/ml) carrying no transgene (AdNull) concurrently with TA injection. Animals were sacrificed one week after AdPLAT or AdNull treatment. Endogenous mRNA expression levels of mouse PAI-1 and MMP-2, -9 and -13 were also measured using qRT-PCR. Outflow facility one week after AdPLAT administration was increased by 60% and 63% respectively for animals that had not or had been pretreated with steroids. Overexpression of PLAT significantly upregulated expression of PAI-1, MMP-2, -9 and -13 compared to the levels found in TA only treated eyes. These findings suggest that overexpression of PLAT in TM of mouse eyes can both prevent and reverse the decrease in outflow facility caused by steroid treatment and is associated with upregulation of MMPs.
authors: Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
authors: Sandeep
authors: S
authors: Kumar
authors: Shaily
authors: S
authors: Shah
authors: Hai Michael
authors: HM
authors: Tang
authors: Matthew
authors: M
authors: Smith
authors: Teresa
authors: T
authors: Borrás
authors: John
authors: J
authors: Danias
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012756:Sheep; D013256:Steroids / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D014129:Trabecular Meshwork / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D013256:Steroids; D010959:Tissue Plasminogen Activator; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D014222:Triamcinolone Acetonide
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