A Viral Model for Corneal Scarring and Neovascularization Following Ocular Infection of Rabbits With a Herpes Simplex Virus Type 1 (HSV-1) Mutant

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Purpose:Herpes simplex virus type 1 (HSV-1) remains a major cause of corneal scarring and visual loss. Although efforts have been made, no reproducible animal model is available to examine recurrent corneal disease. Here we propose a rabbit ocular model to study recurrent corneal disease using an HSV-1 mutant that reactivates with high efficiency.Methods:Rabbits were ocularly infected with 2 × 105 PFU/eye of the parental McKrae, dLAT2903 (a LAT-null virus with a low-reactivation phenotype), or CJLAT (a high-reactivation virus). Acute ocular disease [days 2, 4, 7, and 10 postinfection (pi)], recurrent ocular disease, and neovascularization (days 30 to 58 pi) were monitored.Results:All acute ocular disease symptoms, including conjunctivitis and corneal disease, were similar with all 3 viruses. No corneal scarring was detected in any eyes up to day 30 pi. Between days 35 and 58 pi, corneal scarring was observed in 11/14 (experiment 1) and 18/22 (experiment 2) eyes of CJLAT-infected rabbits. Significantly less corneal scarring was seen in eyes of rabbits infected with McKrae (0/18 and 0/16) or dLAT2903 (0/16 and 3/24) (P < 0.0001). Many of the eyes with corneal scarring developed obvious, measurable neovascularization.Conclusions:Rabbits infected with CJLAT developed corneal scarring and neovascularization similar to that of clinical ocular HSV-1 recurrent disease. Because this occurred well after the acute infection had resolved, the corneal scarring and neovascularization appeared to be recurrent disease. Thus, CJLAT ocular infection of rabbits may provide a good and reproducible animal model to study factors involved in corneal scarring and neovascularization from recurrent ocular HSV-1.

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