Abstract
Purpose: :
To assess the effect of infliximab as an adjunct in the treatment of acute retinal necrosis in a mouse model.
Methods: :
Herpes simplex virus–I, KOS strain, was concentrated to 180pfu in Eagle’s media. 31 BALB/c mice aged 5–6 weeks old were obtained weighing between 26–30 grams. The mice were divided into the 5 subgroups listed below : 1 – 0.5µL Eagle’s media (3)
2 – 0.5µL Eagle’s + HSV (3)
3 – 0.5µL Eagle’s + HSV + 0.5µL Acyclovir (8)
4 – 0.5µL Eagle’s + HSV + 0.5µL Acyclovir + 0.5µL Triamcinolone (8)
5 – 0.5µL Eagle’s + HSV + 0.5µL Acyclovir + 0.5µL Triamcinolone + 0.03mL Infliximab (9)The following concentrations of medication were used : acyclovir 50mg/ml (intraperitoneal), triamcinolone 40mg/ml (intravitreal), and infliximab 10mg/ml (intraperitoneal). The mice were anesthetized and a 3/8 curved 6.6mm Ethicon needle was used to create a superotemporal quadrant sclerotomy (0.5–1mm) in the right eye of each mouse just posterior to the limbus. A 0.5 microliter Hamilton micropipette syringe was used to inject intravitreal Eagle’s media, HSV, and/or triamcinolone. The mice were sacrificed after after four days. Both eyes of each animal were harvested, placed in 10% formalin, and underwent routine histologic processing and staining with hematoxylin and eosin. The eyes were examined by light microscopy and the following findings were assessed : anterior chamber inflammation (minimal, <10%; mild, <25%; moderate, <50%; severe, >50%); vitreous inflammation (minimal, mild, moderate, severe); percentage of retinal detachment; percentage of retina with inflammation or necrosis.
Results: :
Minimal changes were noted between groups in comparing anterior chamber and vitreous reactions. Eyes given injections of acyclovir/triamcinolone/infliximab showed less disruption of retinal architecture when compared to eyes treated with acyclovir/triamcinolone after four days. Only one of seven eyes treated with infliximab had > 5% retinal disruption. Four of eight eyes treated with acyclovir and triamcinolone had > 5% retinal disruption. Five of nine eyes treated with only acylovir or acyclovir with triamcinolone had > 5% retinal disruption.
Conclusions: :
This pilot study has shown the feasibility of using this mouse model in inducing the pathological processes involved in ARN. The addition of infliximab in the treatment of acute retinal necrosis appears to reduce the amount of retinal tissue that is damaged by the normal immunological reaction. Further study with infliximab and its effect on morbidity is warranted.
Keywords: retinochoroiditis • herpes simplex virus • retinitis