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

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

doi:10.1016/j.exer.2014.10.004

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

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

Icahn School of Medicine at Mount Sinai

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

We have previously shown that tissue plasminogen activator (tPA) injected in the vitreous of sheep, reduced or prevented the elevation of the intraocular pressure (IOP) normally produced by the instillation of 1% prednisolone. We now report the effect of tPA when injected into the anterior chamber (AC) in amounts of 0.01, 0.001 and 0.0001μg diluted in a volume of 50μL. Lyophilized tPA, obtained as Actilyse^® 50mg from Boehringer Ingelheim containing arginine was utilized. The Actilyse was diluted in balanced salt solution to obtain the desired amount of tPA in 50μL. An identical solution containing only arginine was prepared to inject into the contralateral eye as a control. Six sheep of the Corriedale breed were selected. At the beginning of the study all eyes received instillation of 1% prednisolone 3times/day for 10days to elevate their IOP from 10mmHg to about 23mmHg. Then, 0.0001μg was injected into one of the eyes and its effect was followed for up to 55:00h while the instillation of prednisolone continued in both eyes. The same protocol was implemented for the 0.001 and 0.01μg amounts after extended washout and IOP was over 22mmHg. The injection of 0.0001μg into the AC had no effect on an IOP of 23.0mmHg at 6:00 and 30:00h after injection. 0.001μg of tPA reduced IOP from 23.1 to 18.6mmHg at 6:00h but IOP recovered to 22.3mmHg at 30:00h. Injection of 0.01μg produced a marked and prolonged reduction of IOP. From a baseline of 23.0, IOP was reduced to 14.0, 14.7, 21.2, and 20.9mmHg at 5.0, 23.0, 27.0 and 45.5h, respectively. The 0.423μg of arginine, which is associated with 0.01μg tPA, was injected alone and had no effect. Recombinant human tPA injected in the AC is effective in reversing steroid-induced IOP elevation in sheep. The reduction of IOP elevation may be the result of an effect on extra-cellular matrix turnover in the TM. These findings suggest that tPA may by useful as a therapeutic agent in steroid-induced glaucomas.

Original language	English
Pages (from-to)	114-116
Number of pages	3
Journal	Experimental Eye Research
Volume	128
DOIs	https://doi.org/10.1016/j.exer.2014.10.004
State	Published - 1 Dec 2014

Keywords

Anterior chamber
Glaucoma
IOP
Sheep
TPA

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10.1016/j.exer.2014.10.004

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@article{36c4cb41b81640a19d2fb6f0eeb5b50e,

title = "Tissue plasminogen activator reduces the elevated intraocular pressure induced by prednisolone in sheep",

abstract = "We have previously shown that tissue plasminogen activator (tPA) injected in the vitreous of sheep, reduced or prevented the elevation of the intraocular pressure (IOP) normally produced by the instillation of 1\% prednisolone. We now report the effect of tPA when injected into the anterior chamber (AC) in amounts of 0.01, 0.001 and 0.0001μg diluted in a volume of 50μL. Lyophilized tPA, obtained as Actilyse{\textregistered} 50mg from Boehringer Ingelheim containing arginine was utilized. The Actilyse was diluted in balanced salt solution to obtain the desired amount of tPA in 50μL. An identical solution containing only arginine was prepared to inject into the contralateral eye as a control. Six sheep of the Corriedale breed were selected. At the beginning of the study all eyes received instillation of 1\% prednisolone 3times/day for 10days to elevate their IOP from 10mmHg to about 23mmHg. Then, 0.0001μg was injected into one of the eyes and its effect was followed for up to 55:00h while the instillation of prednisolone continued in both eyes. The same protocol was implemented for the 0.001 and 0.01μg amounts after extended washout and IOP was over 22mmHg. The injection of 0.0001μg into the AC had no effect on an IOP of 23.0mmHg at 6:00 and 30:00h after injection. 0.001μg of tPA reduced IOP from 23.1 to 18.6mmHg at 6:00h but IOP recovered to 22.3mmHg at 30:00h. Injection of 0.01μg produced a marked and prolonged reduction of IOP. From a baseline of 23.0, IOP was reduced to 14.0, 14.7, 21.2, and 20.9mmHg at 5.0, 23.0, 27.0 and 45.5h, respectively. The 0.423μg of arginine, which is associated with 0.01μg tPA, was injected alone and had no effect. Recombinant human tPA injected in the AC is effective in reversing steroid-induced IOP elevation in sheep. The reduction of IOP elevation may be the result of an effect on extra-cellular matrix turnover in the TM. These findings suggest that tPA may by useful as a therapeutic agent in steroid-induced glaucomas.",

keywords = "Anterior chamber, Glaucoma, IOP, Sheep, TPA",

author = "Candia, \{Oscar A.\} and Gerometta, \{Rosana M.\} and John Danias",

note = "Publisher Copyright: {\textcopyright} 2014 Published by Elsevier Ltd.",

year = "2014",

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day = "1",

doi = "10.1016/j.exer.2014.10.004",

language = "English",

volume = "128",

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T1 - Tissue plasminogen activator reduces the elevated intraocular pressure induced by prednisolone in sheep

AU - Candia, Oscar A.

AU - Gerometta, Rosana M.

AU - Danias, John

PY - 2014/12/1

Y1 - 2014/12/1

N2 - We have previously shown that tissue plasminogen activator (tPA) injected in the vitreous of sheep, reduced or prevented the elevation of the intraocular pressure (IOP) normally produced by the instillation of 1% prednisolone. We now report the effect of tPA when injected into the anterior chamber (AC) in amounts of 0.01, 0.001 and 0.0001μg diluted in a volume of 50μL. Lyophilized tPA, obtained as Actilyse® 50mg from Boehringer Ingelheim containing arginine was utilized. The Actilyse was diluted in balanced salt solution to obtain the desired amount of tPA in 50μL. An identical solution containing only arginine was prepared to inject into the contralateral eye as a control. Six sheep of the Corriedale breed were selected. At the beginning of the study all eyes received instillation of 1% prednisolone 3times/day for 10days to elevate their IOP from 10mmHg to about 23mmHg. Then, 0.0001μg was injected into one of the eyes and its effect was followed for up to 55:00h while the instillation of prednisolone continued in both eyes. The same protocol was implemented for the 0.001 and 0.01μg amounts after extended washout and IOP was over 22mmHg. The injection of 0.0001μg into the AC had no effect on an IOP of 23.0mmHg at 6:00 and 30:00h after injection. 0.001μg of tPA reduced IOP from 23.1 to 18.6mmHg at 6:00h but IOP recovered to 22.3mmHg at 30:00h. Injection of 0.01μg produced a marked and prolonged reduction of IOP. From a baseline of 23.0, IOP was reduced to 14.0, 14.7, 21.2, and 20.9mmHg at 5.0, 23.0, 27.0 and 45.5h, respectively. The 0.423μg of arginine, which is associated with 0.01μg tPA, was injected alone and had no effect. Recombinant human tPA injected in the AC is effective in reversing steroid-induced IOP elevation in sheep. The reduction of IOP elevation may be the result of an effect on extra-cellular matrix turnover in the TM. These findings suggest that tPA may by useful as a therapeutic agent in steroid-induced glaucomas.

AB - We have previously shown that tissue plasminogen activator (tPA) injected in the vitreous of sheep, reduced or prevented the elevation of the intraocular pressure (IOP) normally produced by the instillation of 1% prednisolone. We now report the effect of tPA when injected into the anterior chamber (AC) in amounts of 0.01, 0.001 and 0.0001μg diluted in a volume of 50μL. Lyophilized tPA, obtained as Actilyse® 50mg from Boehringer Ingelheim containing arginine was utilized. The Actilyse was diluted in balanced salt solution to obtain the desired amount of tPA in 50μL. An identical solution containing only arginine was prepared to inject into the contralateral eye as a control. Six sheep of the Corriedale breed were selected. At the beginning of the study all eyes received instillation of 1% prednisolone 3times/day for 10days to elevate their IOP from 10mmHg to about 23mmHg. Then, 0.0001μg was injected into one of the eyes and its effect was followed for up to 55:00h while the instillation of prednisolone continued in both eyes. The same protocol was implemented for the 0.001 and 0.01μg amounts after extended washout and IOP was over 22mmHg. The injection of 0.0001μg into the AC had no effect on an IOP of 23.0mmHg at 6:00 and 30:00h after injection. 0.001μg of tPA reduced IOP from 23.1 to 18.6mmHg at 6:00h but IOP recovered to 22.3mmHg at 30:00h. Injection of 0.01μg produced a marked and prolonged reduction of IOP. From a baseline of 23.0, IOP was reduced to 14.0, 14.7, 21.2, and 20.9mmHg at 5.0, 23.0, 27.0 and 45.5h, respectively. The 0.423μg of arginine, which is associated with 0.01μg tPA, was injected alone and had no effect. Recombinant human tPA injected in the AC is effective in reversing steroid-induced IOP elevation in sheep. The reduction of IOP elevation may be the result of an effect on extra-cellular matrix turnover in the TM. These findings suggest that tPA may by useful as a therapeutic agent in steroid-induced glaucomas.

KW - Anterior chamber

KW - Glaucoma

KW - IOP

KW - Sheep

KW - TPA

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DO - 10.1016/j.exer.2014.10.004

M3 - Article

C2 - 25304217

AN - SCOPUS:84907952949

SN - 0014-4835

VL - 128

SP - 114

EP - 116

JO - Experimental Eye Research

JF - Experimental Eye Research

ER -

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

Abstract

Keywords

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