Chorioretinal disease patterns in congenic mice following intraocular inoculation with HSV-1.
Disease patterns and immunologic parameters were studied employing inbred and Igh-1 disparate congenic mice to determine the role of host genetics and Igh-1-linked gene products in the von Szily model of viral chorioretinitis. Following intracameral inoculation of 1.5 x 10(4) PFU HSV-1 (KOS), 100% of BALB/c (Igh-1a), 62% of A/J (Igh-1e) and none of the C57BL/6J (Igh-1b) inbred mice developed contralateral necrotizing chorioretinitis. Multigenic differences between inbred mice prohibit conclusions about the specific role of Igh-1-linked immune regulation in this model. In order to more exactly define Igh-1-specific restriction of HSV-1-mediated chorioretinitis, Igh-1-disparate, congenic BALB/c mice were studied following both anterior chamber and intravitreal inoculation protocols. Anterior chamber inoculation resulted in contralateral retinal necrosis in 75% of BALB/c (Igh-1a) mice, 30% of C.AL-20 (Igh-1d) and 5% of the C.B-17 (Igh-1b) congenic mice; all strains showed ipsilateral retinal sparing. Following intravitreal inoculation of HSV-1 a similar restricted disease pattern was found in contralateral eyes. Contralateral chorioretinitis developed in 30% of BALB/c, 15% of C.AL-20 and 6% of C.B-17 mice. Ipsilateral disease, however, was found in all murine strains. These disease patterns developed despite equivalent suppression of systemic DTH and equivalent RPE permissivity to viral replication. These data demonstrate that host genetics strongly regulates contralateral HSV-1-mediated chorioretinal disease patterns by a mechanism unrelated to the development of systemic suppression of DTH and specifically support a dominant role for gene products linked to the Igh-1 locus in the immunomodulation of ocular disease.
Opremcak
E M
EM
Department of Ophthalmology, Ohio State University, Columbus 43210.
Foster
C S
CS
Hemady
R
R
Rice
B A
BA
Daigle
J A
JA
Raizman
M B
MB
Chung
H
H
Zaltas
M
M
D000818:Animals; D002825:Chorioretinitis / Q000209:etiology* / Q000473:pathology; D005123:Eye; D006561:Herpes Simplex / Q000150:complications / Q000382:microbiology; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007267:Injections; D051379:Mice; D008815:Mice, Inbred Strains; D010857:Pigment Epithelium of Eye / Q000382:microbiology; D018139:Simplexvirus / Q000502:physiology; D014779:Virus Replication