Abstract
The purpose of this study was to evaluate the efficacy of a Coulomb Controlled Iontophoresis system (CCI) in the local delivery of corticosteroids for the treatment of uveitis. The therapeutic efficacy of Dexamethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the absence of electrical current. The evaluation was done in the treatment of the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered either at the time of LPS injection or 5 hours later. For iontophoresis, we used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current was of 400 μA during four minutes with a total surface charge of 0.4 C cm-2. EIU was evaluated by clinical examination, by counts of intraocular inflammatory cells on histological sections, and by measuring the protein levels in the aqueous humor and in the vitreous. The TNF-α gene expression in the iris and ciliary body, and in the retina was evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-α in EIU. Our results demonstrated that local administration of Dex by CCI inhibited anterior and posterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anterior and posterior segments of the eye, the protein exudation, TNF levels and the cellular infiltration were inhibited. The TNF-α gene expression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CCI apparatus. In conclusion, CCI administration of Dex allows for a therapeutic effect on the posterior as well as the anterior segment of the eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations.
| Original language | English |
|---|---|
| Pages (from-to) | 533-545 |
| Number of pages | 13 |
| Journal | Experimental Eye Research |
| Volume | 65 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 1 1997 |
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Keywords
- Drug-delivery
- EIU
- Glucocorticoids
- Iontophoresis
- Rat
- TNF-α
ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
Cite this
Iontophoresis of dexamethasone in the treatment of endotoxin-induced- uveitis in rats. / Behar-Cohen, Francine F.; Parel, Jean-Marie A; Pouliquen, Yves; Thillaye-Goldenberg, Beatrice; Goureau, Olivier; Heydolph, Silke; Courtois, Yves; De Kozak, Yvonne.
In: Experimental Eye Research, Vol. 65, No. 4, 01.10.1997, p. 533-545.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Iontophoresis of dexamethasone in the treatment of endotoxin-induced- uveitis in rats
AU - Behar-Cohen, Francine F.
AU - Parel, Jean-Marie A
AU - Pouliquen, Yves
AU - Thillaye-Goldenberg, Beatrice
AU - Goureau, Olivier
AU - Heydolph, Silke
AU - Courtois, Yves
AU - De Kozak, Yvonne
PY - 1997/10/1
Y1 - 1997/10/1
N2 - The purpose of this study was to evaluate the efficacy of a Coulomb Controlled Iontophoresis system (CCI) in the local delivery of corticosteroids for the treatment of uveitis. The therapeutic efficacy of Dexamethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the absence of electrical current. The evaluation was done in the treatment of the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered either at the time of LPS injection or 5 hours later. For iontophoresis, we used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current was of 400 μA during four minutes with a total surface charge of 0.4 C cm-2. EIU was evaluated by clinical examination, by counts of intraocular inflammatory cells on histological sections, and by measuring the protein levels in the aqueous humor and in the vitreous. The TNF-α gene expression in the iris and ciliary body, and in the retina was evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-α in EIU. Our results demonstrated that local administration of Dex by CCI inhibited anterior and posterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anterior and posterior segments of the eye, the protein exudation, TNF levels and the cellular infiltration were inhibited. The TNF-α gene expression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CCI apparatus. In conclusion, CCI administration of Dex allows for a therapeutic effect on the posterior as well as the anterior segment of the eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations.
AB - The purpose of this study was to evaluate the efficacy of a Coulomb Controlled Iontophoresis system (CCI) in the local delivery of corticosteroids for the treatment of uveitis. The therapeutic efficacy of Dexamethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the absence of electrical current. The evaluation was done in the treatment of the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered either at the time of LPS injection or 5 hours later. For iontophoresis, we used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current was of 400 μA during four minutes with a total surface charge of 0.4 C cm-2. EIU was evaluated by clinical examination, by counts of intraocular inflammatory cells on histological sections, and by measuring the protein levels in the aqueous humor and in the vitreous. The TNF-α gene expression in the iris and ciliary body, and in the retina was evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-α in EIU. Our results demonstrated that local administration of Dex by CCI inhibited anterior and posterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anterior and posterior segments of the eye, the protein exudation, TNF levels and the cellular infiltration were inhibited. The TNF-α gene expression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CCI apparatus. In conclusion, CCI administration of Dex allows for a therapeutic effect on the posterior as well as the anterior segment of the eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations.
KW - Drug-delivery
KW - EIU
KW - Glucocorticoids
KW - Iontophoresis
KW - Rat
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=0030700775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030700775&partnerID=8YFLogxK
U2 - 10.1006/exer.1997.0364
DO - 10.1006/exer.1997.0364
M3 - Article
VL - 65
SP - 533
EP - 545
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 4
ER -