A viral model for corneal scarring and neovascularization following ocular infection of rabbits with a herpes simplex virus type 1 (HSV-1) mutant.
OBJECTIVE
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 x 10 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.
Barsam
Charles A
CA
Department of Ophthalmology, College of Medicine, University of California at Irvine, 92868, USA.
Brick
David J
DJ
Jones
Clinton
C
Wechsler
Steven L
SL
Perng
Guey-Chuen
GC
D000818:Animals; D002921:Cicatrix / Q000473:pathology / Q000821:virology*; D003315:Cornea / Q000098:blood supply*; D003316:Corneal Diseases / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D016679:Genome, Viral; D006561:Herpes Simplex / Q000150:complications*; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000821:virology*; D011817:Rabbits; D017735:Virus Latency