Download Two simple animal models of intraocular pressure elevation for testing

Two simple animal models of intraocular pressure elevation for testing
therapeutic drugs in glaucoma
Sophie GRILLO-ANTONELLI, Nicolas CIMBOLINI, Laurence FERAILLE, Pierre-Paul ELENA. Iris Pharma, La Gaude, France.
Results
Naive NaCl 2.5% + brimonidine 0.2% dexamethasone 0.1% 30 20 *
*
*
50 100 150 200 250 B
300 350 -­‐4 *
*
*
*
*
5 0 0 -­‐10 20 40 60 80 100 120 140 160 180 200 -­‐5 D
C
15 *
*
10 -­‐8 Time (min)
Time (min)
10 The high IOP was significantly decreased after treatment with single drop
application of brimonidine/timolol (0.2%/0.25%).
5 0 Baseline D7 D14 D21 Time (Days)
D28 D35 D42 NaCl 0,9% NaCl 2.5% Here we described two models of high intraocular pressure, a chronic in
rat and an acute in rabbit. Two different classes of drug, a
prostanglandin analogue and a combinaison of beta blocker and alpha
agonist eye drops, have been efficient to lower IOP in the rat model and
the alpha agonist eye drops, in the rabbit model. These two models with
simple experimental handling and low cost, can be used as a tool for
discovering therapeutic drugs in glaucoma targeting the outflow.
14 12 dexamethasone 0.1% + latanoprost 0.002% 10 dexamethasone 0.1% + NaCl 0.9% 10 Naive 8 6 4 8 0 0 1 2 3 4 5 6 7 -­‐2 0 -­‐4 -­‐6 *
4 2 0 *
6 2 -­‐2 *
The pretreatment with brimonidine 0.2% prevented the raise of IOP induced by
the 2.5% NaCl intravitreal injection.
Conclusion
The rabbit model
0.1% dexamethasone instillations induced a significant and chronic increase of
the IOP over 35 days.
∆IOP (mmHg)
15 400 -­‐2 -­‐6 25 IOP (mmHg)
0 A
NaCl 2.5% + NaCl 0.9% 20 0 The rat model
Materials and methods
The rabbit model:
Elevation of IOP
Elevation of IOP in male New Zealand rabbits was induced by
intravitreal (IVT) injection of a hypertonic saline solution (2.5% NaCl).
The animals of the control group received an IVT injection of isotonic
saline solution (0.9% NaCl) (n=10 per group).
Hypotensive drug assay
In order to test efficacy of hypotensive drug in the model, brimonidine
(0.2%) or 0.9% NaCl were applied five time during the two hours
preceeding the IVT injection of hypertonic saline solution (n=10 per
group).
dexamethasone 0,1% + NaCl 0.9% 2 Naive The rat model:
Elevation of IOP
Young female Sprague-Dawley rats received bilateral topical application
of dexamethasone 0.1% twice daily over 42 days1. The animals of naive
group were instilled by 0.9% NaCl only (n=10 per group).
Hypotensive drug assay
On day 28, the IOP lowering effect of bilateral single drop application of
latanoprost (0.002%)4 or brimonidine/timolol (0.2%/0.25%) was
evaluated in high IOP rats. The naive group and an induced group
treated with bilateral single drop application of 0.9% NaCl served as
controls (n=10 per group).
IOP measurement
The IOP was measured using an Icare® TonoLab tonometer at different
time-points.
dexamethasone 0.1% + (@molol 0.25% + brimonidine 0.2%) ∆ IOP (mmHg)
Glaucoma is a progressive optic neuropathy and elevated intraocular
pressure (IOP) is one of the most important risk factors. There are many
experimental models to test the effect of new drugs but they are often
expensive or require invasive techniques. The purpose of this poster is
to present two simple animal models of intraocular pressure elevation for
testing therapeutic drugs in glaucoma.
One is related to the side effects of corticosteroids in rats1,2 and the
other one is related to the hypersaline stress in rabbits eye3.
IOP measurement
The IOP was recorded with a Reichert MODEL 30 CLASSIC™
pneumatonometer at different time-points.
∆IOP (mmHg)
Introduction
∆IOP (mmHg)
Poster T017
50 100 150 200 250 300 350 References
Time (min)
* (h)
Time
*
The high IOP was significantly decreased after treatment with single drop
application of latanoprost (0.002%).
2.5% NaCl intravitreal injection induced a significant increase of IOP during 2
hours.
Statistical analysis
Data were compared using two-way ANOVA p<0,05
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1. 
2. 
3. 
4. 
Argawal et al. ISOPT (Paris 2013).
Jain D et al. Journal of Current Glaucoma Practice. 4(3):109-113 (2010).
Orihashi M et al. Biol. Pharm. Bull. 28 (1) 65-68 (2005).
S. Husain et al. Exp. Eye Res. 48, 707-716 (2006).