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Abstract #90747 Published in IGR 21-3
Tissue plasminogen activator attenuates outflow facility reduction in mouse model of juvenile open angle glaucoma
Gindina S; Hu Y; Barron AO; Qureshi Z; Danias JExperimental Eye Research 2020; 199: 108179
Tissue plasminogen activator (tPA) has been shown to prevent steroid-induced reduction in aqueous humor outflow facility via an upregulation in matrix metalloproteinase (Mmp) expression. The purpose of this study was to determine whether tPA can rescue outflow facility reduction in the Tg-MYOC mouse model, which replicates human juvenile open angle glaucoma. Outflow facility was measured in Tg-MYOC mice following: periocular steroid exposure and intraocular protein treatment with enzymatically active or enzymatically inactive tPA. Effects of tPA on outflow facility were compared to those of animals treated with topical sodium phenylbutarate (PBA), a modulator of endoplasmic reticulum stress. Gene expression of fibrinolytic pathway components (Plat, Plau, and Pai-1) and matrix metalloproteinases (Mmp-2, -9, and -13) was determined in angle ring tissues containing the trabecular meshwork. Tg-MYOC mice did not display further outflow facility reduction following steroid exposure. Enzymatically active and enzymatically inactive tPA were equally effective in attenuating outflow facility reduction in Tg-MYOC mice and caused enhanced expression of matrix metalloproteinases (Mmp-9 and Mmp-13). tPA was equally effective to topical PBA treatment in ameliorating outflow facility reduction in Tg-MYOC mice. Both treatments were associated with an upregulation in Mmp-9 expression while tPA also upregulated Mmp-13 expression. tPA increases the expression of matrix metalloproteinases and may cause extracellular matrix remodeling at the trabecular meshwork, which results in reversal of outflow facility reduction in Tg-MYOC mice.
Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; Department of Ophthalmology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA. Electronic address: Sofya.Gindina@downstate.edu.
Full articleClassification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
9.1.2 Juvenile glaucoma (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
2.6.2.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics > 2.6.2 Outflow)
