Rhodopsin-induced experimental autoimmune uveoretinitis: dose-dependent clinicopathological features.
We have studied the clinicopathological features of experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by injection of different doses of rhodopsin and its illuminated form opsin. Rhodopsin consistently appears to be more pathogenic than opsin. Injected in Freund's complete adjuvant and pertussis adjuvant 50 micrograms of rhodopsin induces a frequency of severe EAU similar to 250 micrograms of opsin. Intensity, frequency and location of ocular inflammation are markedly dose dependent. At high dose (100-250 micrograms), rhodopsin induces severe bilateral uveoretinitis in all animals, which starts with acute inflammation of the anterior eye segment at day 10-12 followed by chorioretinitis (predominantly retinitis) which results in complete elimination of the photoreceptor cells. At low dose (20 micrograms), rhodopsin induces mild transient inflammation in 60% of the animals, mainly consisting of mild posterior retinitis which starts at day 20 and leads to a typical multiple focal destruction of the photoreceptor cells. Intermediate doses cause an intermediate type of disease. Omission of pertussis adjuvant lowers the frequency of severe disease at low doses of rhodopsin, delays its onset and changes its features. The last characteristic has been observed in particular at intermediate doses (50-100 micrograms). In these cases, EAU usually starts by cell infiltration of the vitreous, while the anterior segment is only mildly affected. Without pertussis adjuvant the pathogenicity of opsin is low. Even in both adjuvants severe EAU can only be evoked by a high dose of opsin. Although there exists a marked difference in uveitogenicity between rhodopsin and opsin, the immunogenicity is similar and seems not to be correlated with their pathogenicity.
Schalken
J J
JJ
Institute of Ophthalmology, University of Nijmegen, The Netherlands.
Winkens
H J
HJ
van Vugt
A H
AH
Bovée-Geurts
P H
PH
de Grip
W J
WJ
Broekhuyse
R M
RM
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D004306:Dose-Response Relationship, Immunologic; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D051381:Rats; D011917:Rats, Inbred Lew; D012168:Retinal Pigments / Q000008:administration & dosage*; D012173:Retinitis / Q000209:etiology* / Q000473:pathology; D012243:Rhodopsin / Q000008:administration & dosage* / Q000276:immunology; D017299:Rod Opsins; D013997:Time Factors; D014605:Uveitis / Q000209:etiology* / Q000473:pathology
D005136:Eye Proteins; D012168:Retinal Pigments; D017299:Rod Opsins; D012243:Rhodopsin