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Abstract
Purpose
We investigated the therapeutic effects of monoclonal anti-TNF antibody (infliximab) on experimental uveitis.
Methods
Twenty New Zealand White rabbits were immunized with Mycobacterium tuberculosis H37Ra antigen and then challenged with intravitreal injection of tuberculin antigen to introduce a uveitis. Then infliximab was injected into rabbit eyes at an intravenous concentration of 5 mg/kg and intravitreal concentrations of 1 mg/0.1mL and 100 microg/0.1mL. As a control, the vehicle was injected intravenously or intravitreally. To evaluate the therapeutic effects, inflammation was assessed by slit lamp biomicroscopy and scored according to the severity of inflammation. The animals were also evaluated by electroretinography and histopathology.
Results
Regardless of the administration route, inflammatory activities of anterior chamber and engorgement of vascular structures were reduced in the infliximab treated group compared to control. Different administration routes and different concentrations of infliximab did not affect the therapeutic outcome of the clinical scoring. Intravenous (5 mg/kg) and intravitreal diluted (100 microg/0.1mL) infliximab injection groups showed significant improvement in electroretinographic findings and significant reduction of inflammatory cells with preservation of retinal tissue architecture on histopathologic examination. However, focal loss of the photoreceptor outer segment is observed in intravitreal undiluted (1 mg/0.1 mL) infliximab injected eyes. Conclusions: Infliximab may be a useful treatment modality to suppress ocular inflammation in experimental uveitis models in rabbits.
References
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Figure 1.
In the treated eye, dilated iris blood vessel and hazy anterior chamber (A) improved after intravenous infliximab treatment (B) In contrast, the untreated eye showed marked conjunctival injection and inflammation of the anterior chamber (C) and unchanged after intravenous BSS treatment (D).
Figure 2.
Clinical grades of inflammation in each group.
Group I: Intravenous BSS-injected eye. (n=4)
Group II: Intravitreal BSS-injected eye. (n=4)
Group III: Intravenous infliximab (5 mg/kg)-injected eye. (n=4)
Group IV: Intravitreal infliximab (1 mg/0.1 ml)-injected eye. (n=4)
Group V: Intravitreal infliximab (100 μg/0.1 ml)-injected eye. (n=4)
*: statistically significant.
Figure 3.
Ratio of b-wave amplitude (uveitis-induced fellow eye) in each group. (open bars = after induction of uveitis, filled bars = after administration of drugs)
Group I : Intravenous BSS-injected eye. (n=4)
Group II: Intravitreal BSS-injected eye. (n=4)
Group III: Intravenous infliximab (5 mg/kg)-injected eye. (n=4)
Group IV: Intravitreal infliximab (1 mg/0.1ml)-injected eye. (n=4)
Group V: Intravitreal infliximab (100 μg/0.1ml)-injected eye. (n=4)
*: statistically significant.
Figure 4.
Histopathologic changes of the retina on day 7 after the administration of drugs.
Note the loss of photoreceptor outer segment and infiltration of inflammatory cells in intravenous BSS-injected eye (A) and intravitreal BSS-injected eye (B). In intravitreal infliximab (1 mg/0.1 ml)-injected eye (D), some loss of photoreceptor outer segment is also observed. Otherwise retinal tissue architectures are well preserved in intravenous infliximab (5 mg/kg)-injected eye (C) and intravitreal infliximab (100 pig/0.1 ml)-injected eye (E).
(A) Intravenous BSS-injected eye.
(B) Intravitreal BSS-injected eye.
(C) Intravenous infliximab (5 mg/kg)-injected eye.
(D) Intravitreal infliximab (1 mg/0.1 ml)-injected eye.
(E) Intravitreal infliximab (100 gg/0.1 ml)-injected eye.
Figure 5.
Histopathologic grade in each group.
Group I.: Intravenous BSS-injected eye. (n=4)
Group II: Intravitreal BSS-injected eye. (n=4)
Group III: Intravenous infliximab (5 mg/kg)-injected eye. (n=4)
Group IV: Intravitreal infliximab (1 mg/0.1 ml)-injected eye. (n=4)
Group V: Intravitreal infliximab (100 pg/0.1 ml)-injected eye. (n=4)
* : statistically significant.
Table 1.
Clinical grading of experiment uveitis
Table 2.
Histopathological grading of experimental uveitis
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