Reduction of Steroid-Induced Intraocular Pressure Elevation in Sheep by Tissue Plasminogen Activator

Gerometta, Rosana; Kumar, Sandeep; Shah, Shaily; Alvarez, Larry; Candia, Oscar A.; Danias, John

doi:10.1167/iovs.13-12801

Cited by 23 publications

(21 citation statements)

References 47 publications

(62 reference statements)

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“…In patients with hyphema, IOP can raise in acute phase because of trabecular meshwork blockage by clot, red blood cells, or inflammatory debris [3,14,18,19]. And also high dose steroids may suppress phagocyctic activity which may lead to observations such as clot, red blood cells, inflammatory debris or increased deposition of material in the juxtacanalicular meshwork of eyes [20,21]. Our patients in group I received high dose steroid (prednisolone asetat, 12 times a day), and our IOP outcomes may be due to high dose steroid.…”

Section: Discussionmentioning

confidence: 99%

Is topical corticosteroid necessary in traumatic hyphema?

Türkoğlu

Çelik²,

Çelik

et al. 2014

Journal Français d'Ophtalmologie

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Section: Discussionmentioning

confidence: 99%

Is topical corticosteroid necessary in traumatic hyphema?

Türkoğlu

Çelik²,

Çelik

et al. 2014

Journal Français d'Ophtalmologie

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“…All of these induced elevated IOP in mouse and/or rat eyes. Over-expression of the serine protease tissue plasminogen activator by adenovirus was found to reduce and reverse elevated IOP in steroid-induced glaucoma in mice and sheep (Gerometta et al, 2013; Kumar et al, 2013). Cochlin was identified as a protein that was up-regulated in glaucoma trabecular meshwork using proteomics (Bhattacharya et al, 2005).…”

Section: Application Of Virus To Manipulate Ecm In Animal Modelsmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork: Intraocular pressure regulation and dysregulation in glaucoma

Vranka

Kelley

Acott

et al. 2015

Experimental Eye Research

314

291

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The trabecular meshwork (TM) is located in the anterior segment of the eye and is responsible for regulating the outflow of aqueous humor. Increased resistance to aqueous outflow causes intraocular pressure to increase, which is the primary risk factor for glaucoma. TM cells reside on a series of fenestrated beams and sheets through which the aqueous humor flows to exit the anterior chamber via Schlemm’s canal. The outer trabecular cells are phagocytic and are thought to function as a pre-filter. However, most of the outflow resistance is thought to be from the extracellular matrix (ECM) of the juxtacanalicular region, the deepest portion of the TM, and from the inner wall basement membrane of Schlemm’s canal. It is becoming increasingly evident that the extracellular milieu is important in maintaining the integrity of the TM. Not only have ultrastructural changes been observed in the ECM of the TM in glaucoma, and a significant number of mutations in ECM genes are known to be associated with glaucoma, but the stiffness of glaucomatous TM appears to be greater than that of normal tissue. Additionally, TGFβ2 has been found to be elevated in the aqueous humor of glaucoma patients and is assumed to be involved in ECM changes deep with the juxtacanalicular region of the TM. This review summarizes the current literature on trabecular ECM as well as the development and function of the TM. Animal models and organ culture models targeting specific ECM molecules to investigate the mechanisms of glaucoma are described. Finally, the growing number of mutations that have been identified in ECM genes and genes that modulate ECM in humans with glaucoma are documented.

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“…MMP9-deficient mice were found to have increased IOP compared to wild-type littermates (Robertson et al, 2013). Other proteinases such as PLG (plasminogen) and plasminogen activators (PLAT and PLAU), which serve to convert pro-MMPs to their active form, have also been implicated (Candia et al, 2014; Gerometta et al, 2013). …”

Section: Physiology and Pathogenesismentioning

confidence: 99%

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

Fini

Schwartz

Gao

et al. 2017

Progress in Retinal and Eye Research

126

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Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative®, announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine.

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Reduction of Steroid-Induced Intraocular Pressure Elevation in Sheep by Tissue Plasminogen Activator

Abstract: Recombinant human tPA is effective in both preventing and reversing steroid-induced IOP elevation in sheep. Tissue plasminogen activator may be useful as a therapeutic agent in steroid-induced glaucoma.

Cited by 23 publications

References 47 publications

Is topical corticosteroid necessary in traumatic hyphema?

Is topical corticosteroid necessary in traumatic hyphema?

Extracellular matrix in the trabecular meshwork: Intraocular pressure regulation and dysregulation in glaucoma

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

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