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An ocular model of adenovirus type 5 infection in the NZ rabbit
Y J Gordon1, E Romanowski, T Araullo-Cruz
1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pennsylvania.
Abstract:
Ocular adenoviral infections occur worldwide, and currently, there is no ocular animal model for evaluating new antivirals or studying pathogenesis. With a paired-eye design, an ocular model was developed in 32 New Zealand rabbits following topical and intrastromal inoculation with a clinical isolate of adenovirus type 5 (Ad5 McEwen). Clinical signs of infection--conjunctivitis, corneal edema, subepithelial infiltrates, and iritis--and seroconversion were evaluated. Replicating virus on the ocular surface was determined by serial ocular titers. Reproducible acute ocular infection was demonstrated in 32 of 32 infected eyes (100%), with mean viral replication lasting for 8.3 days. Peak ocular viral titers (10(3) plaque forming units/ml) were achieved on day three after inoculation and represented a 2 log increase (100 times) over day one. Ocular viral replication was associated with acute conjunctivitis (24/34 eyes, 75%), and delayed-onset presumed immune-mediated clinical disease was associated with: blepharoconjunctivitis (21/32 eyes, 66%), iritis (29/32 eyes, 91%), corneal edema (32/32 eyes, 100%), and subepithelial corneal infiltrates (30/32 eyes, 94%). Seroconversion was demonstrated in 26 of 31 rabbits (84%). The study concludes that a potentially useful animal model of adenoviral ocular infection can be attained.
Insights
Researchers developed a new rabbit model for ocular adenovirus infections. This model shows reproducible infection and aids in studying viral pathogenesis and new antiviral treatments.
Area of Science:
- Ophthalmology
- Virology
- Animal Models
Background:
- Ocular adenoviral infections are a global health concern.
- Existing animal models are insufficient for studying adenovirus pathogenesis and evaluating antivirals.
Purpose of the Study:
- To develop and validate a New Zealand rabbit model for ocular adenovirus infection.
- To assess the model's utility in mimicking clinical signs and viral replication.
Main Methods:
- A paired-eye design was used with topical and intrastromal inoculation of adenovirus type 5 (Ad5 McEwen).
- Clinical signs, seroconversion, and ocular viral titers were monitored.
- Viral replication was quantified using serial ocular titers.
Main Results:
- A reproducible ocular infection model was established in 100% of rabbits.
- Mean viral replication persisted for 8.3 days, with peak titers on day three.
- Clinical signs included conjunctivitis, corneal edema, iritis, and subepithelial infiltrates, with high incidence.
Conclusions:
- The developed rabbit model effectively replicates key features of adenoviral ocular infection.
- This model shows potential for evaluating antiviral efficacy and understanding disease mechanisms.