Steroid glaucoma: Corticosteroid-induced ocular hypertension in cats

Zhan, G.; Miranda, Olivia C.; Bito, Laszlo Z.

doi:10.1016/s0014-4835(05)80210-6

Cited by 80 publications

(51 citation statements)

References 14 publications

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“…Glucocorticoid-induced ocular hypertension has been studied in several animal models, including monkeys (41), cows (42), cats (43), rabbits (44), sheep (45), rats (46), and recently mice (47). However, a model of glucocorticoid-induced glaucoma has not previously been developed.…”

Section: Discussionmentioning

confidence: 99%

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

Zode¹,

et al. 2014

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Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasoneinduced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma.

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Section: Discussionmentioning

confidence: 99%

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

Zode¹,

et al. 2014

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“…6 Moderate elevations of IOP may be produced in cats by topical administration of corticosteroids. 7 Corticosteroid-induced ocular hypertension may be induced in cynomolgus monkeys as well; in one series, 5 of 11 monkeys treated with topical dexamethasone showed increased IOP. 8 Many investigations have been reported that study the effects of glucocorticoids on the trabecular meshwork in an attempt to unravel the family of diseases called glaucoma.…”

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confidence: 99%

Steroid-Induced Ocular Hypertension in Normal Cattle

Gerometta¹

2004

Arch Ophthalmol

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To determine whether the bovine eye develops elevation of intraocular pressure (IOP) in response to topical corticosteroid use and to develop a reliable model of steroid-induced elevation of IOP in an animal.Methods: Intraocular pressure was monitored by Perkins applanation tonometry in a group of 12 cows receiving topically administered prednisolone acetate in 1 eye 3 times a day for a period of 49 days after the establishment of baseline IOP values. Perkins readings were converted to IOP in mm Hg using calibration curves derived from in vitro cannulation manometric experiments and validated with in vivo manometric measurements. Intraocular pressure was also monitored for 50 days after the discontinuation of corticosteroid therapy.Results: Intraocular pressure began to increase after 3 weeks of treatment in 100% of the cow eyes receiving corticosteroid and reached a peak 1 week later. Peak interocular IOP differences between the corticosteroid-treated eye and the fellow control eye reached up to 15 mm Hg and began to decline after the discontinuation of treatment but remained significantly elevated for a period of 3 more weeks.Conclusions: Bovine eyes exhibit a robust steroidinduced ocular hypertensive response, with 100% occurrence in this trial. The IOP elevation caused by corticosteroid slowly subsides after discontinuation of treatment.Clinical Relevance: The mechanisms of steroidinduced glaucoma may be related to those involved in primary open-angle glaucoma and could provide the clues to elucidate the pathogenesis of the latter. The high prevalence of corticosteroid-induced elevation of IOP in the cow and the large amount of tissue available will permit studies on the mechanism of this phenomenon not previously possible.

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“…The efficacy of glaucoma therapeutics has historically been well predicted using these two normotensive animal models, which provide good simulations of human ocular outflow anatomy and physiology (Zhan et al, 1992;Sagara et al, 1999;Wang et al, 1999Wang et al, , 2007Stjernschantz, 2001;Gabelt et al, 2003;Rasmussen and Kaufman, 2005;Toris et al, 2006). Although challenges remain, especially the identification of a therapeutic transgene(s), the potential clinical benefits of gene therapy for glaucoma are appealing.…”

Section: Discussionmentioning

confidence: 99%

Prolonged transgene expression with lentiviral vectors in the aqueous humor outflow pathway of non-human primates

Poeschla¹,

Barraza²,

Rasmussen³

et al. 2008

Human Gene Therapy

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We injected lentiviral vectors into the eyes of live nonhuman primates to assess potential for glaucoma gene therapy. Anterior chambers of five cynomolgus monkeys were injected with green fluorescent protein (GFP)-encoding feline immunodeficiency viral vectors. The monkeys were monitored for in vivo transgene expression and clinical parameters. Their eyes were harvested 2-15 months postinjection for tissue analyses. All seven eyes injected with 1.0-2.0Â10 8 transducing units (TU) showed substantial GFP fluorescence in the trabecular meshwork (TM), which was observable even by goniophotographic monitoring for up to 15 months. Only the lowest dose (0.03Â10 8 TU) failed to result in TM fluorescence detectable in vivo, and five of the eight vectorinjected eyes continued to display substantial GFP expression when enucleated eyes were examined at 2, 7, or 15 months postinjection. Some transduced cells were also detected in the iris and ciliary body. Mild, transient postinjection inflammatory responses exceeding that induced by a control saline injection were observed, but vectors did not raise intraocular pressure and were well tolerated. The results demonstrate the first lentiviral vector transduction of the nonhuman primate aqueous humor outflow pathway and support application of the system to human glaucoma gene therapy.

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Steroid glaucoma: Corticosteroid-induced ocular hypertension in cats

Cited by 80 publications

References 14 publications

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

Steroid-Induced Ocular Hypertension in Normal Cattle

Prolonged transgene expression with lentiviral vectors in the aqueous humor outflow pathway of non-human primates

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