Tissue plasminogen activator reduces the elevated intraocular pressure induced by prednisolone in sheep

Candia, Oscar A.; Gerometta, Rosana; Danias, John

doi:10.1016/j.exer.2014.10.004

Cited by 16 publications

(13 citation statements)

References 13 publications

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“…Outflow facility was significantly elevated in eyes exhibiting the highest AdPLAT activity, while other eyes that received AdPLAT but with low expression did not differ from eyes receiving TA alone. These data are consistent with other studies in sheep showing intravitreal (Gerometta et al, 2013) or intracameral (Candia et al, 2014) injection of tPA lowered IOPs of sheep with prednisolone acetate-induced ocular hypertension. AdPLAT expression induced up-regulation of PAI-1 (plasminogen activator inhibitor-1), MMP (matrix metalloproteinases) −2, −9 and −13 compared to levels in eyes treated with TA.…”

Section: Mouse Models Of Gc-oht and Glaucomasupporting

confidence: 93%

“…DEX may also influence the expression of proteolytic enzymes that regulate ECM turn-over, including matrix metalloproteinases and tissue plasminogen activator (tPA) (Samples et al, 1993; Snyder et al, 1993; el-Shabrawi et al, 2000). Recombinant tPA inhibits the IOP elevation induced by prednisolone in sheep (Gerometta et al, 2013; Candia et al, 2014) and the increase in outflow resistance induced by triamcinolone acetonide in mice (Kumar et al, 2013b). …”

Section: Mechanisms Of Gc-induced Ohtmentioning

confidence: 99%

“…Anecortave acetate blocked the GC mediated decrease in the aqueous humor outflow facility, suggesting activity directly on the TM. Either intravitreal (Gerometta et al, 2013) or intracameral (Candia et al, 2014) injection of tPA lowered IOPs of sheep with prednisolone acetate-induced ocular hypertension. IOP lowering by tPA may be mediated by enhancing extracellular matrix turnover in the TM.…”

Section: Animal Models Of Gc-ohtmentioning

confidence: 99%

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Animal models of glucocorticoid-induced glaucoma

Overby

Clark

2015

Experimental Eye Research

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Glucocorticoid (GC) therapy is widely used to treat a variety of inflammatory diseases and conditions. While unmatched in their anti-inflammatory and immunosuppressive activities, GC therapy is often associated with the significant ocular side effect of GC-induced ocular hypertension (OHT) and iatrogenic open-angle glaucoma. Investigators have generated GC-induced OHT and glaucoma in at least 8 different species besides man. These models mimic many features of this condition in man and provide morphologic and molecular insights into the pathogenesis of GC-OHT. In addition, there are many clinical, morphological, and molecular similarities between GC-induced glaucoma and primary open-angle glaucoma (POAG), making animals models of GC-induced OHT and glaucoma attractive models in which to study specific aspects of POAG.

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Section: Mouse Models Of Gc-oht and Glaucomasupporting

confidence: 93%

Section: Mechanisms Of Gc-induced Ohtmentioning

confidence: 99%

Section: Animal Models Of Gc-ohtmentioning

confidence: 99%

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Animal models of glucocorticoid-induced glaucoma

Overby

Clark

2015

Experimental Eye Research

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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

117

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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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“…Similarly, treatment with anterior juxtascleral administration of anecortave acetate has been shown to prevent IOP elevation in sheep (Candia et al, 2010). The sheep model has also been used to determine that tPA can prevent as well as reverse steroid-induced IOP elevation (Candia et al, 2014; Gerometta et al, 2013). More recently we have utilized tPA topically (in the form of eye-drops) to achieve robust IOP lowering in the ovine steroid-induced IOP elevation model (see Figure 1).…”

Section: In Vivo-modelsmentioning

confidence: 99%

Model systems for the study of steroid-induced IOP elevation

Rybkin

Gerometta

Fridman

et al. 2017

Experimental Eye Research

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Steroid-induced IOP elevation affects a significant number of patients. It results from a decrease in outflow facility of the aqueous humor. To understand the pathophysiology of this condition a number of model systems have been created. These include ex-vivo cell and organ cultures as well as in-vivo animal models in organisms ranging from rodents to primates. These model systems can be used to investigate specific aspects of steroid-induced IOP elevation. This brief review summarizes the strengths and limitations of the various model systems and provides examples of where these systems have been successfully used to advance our understanding of steroid-induced IOP elevation.

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Tissue plasminogen activator reduces the elevated intraocular pressure induced by prednisolone in sheep

Cited by 16 publications

References 13 publications

Animal models of glucocorticoid-induced glaucoma

Animal models of glucocorticoid-induced glaucoma

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

Model systems for the study of steroid-induced IOP elevation

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