Effects of heme oxygenase-1 inducer and inhibitor on experimental autoimmune uveoretinitis.
OBJECTIVE
Experimental autoimmune uveoretinitis (EAU) is an animal model of posterior uveitis and heme oxygenase-1 (HO-1) is a well-known anti-oxidant factor. However, there is no report a protective role of HO-1 on EAU in vivo. To verify that HO-1 is induced in EAU by interphotoreceptor retinoid-binding protein (IRBP), that an HO-1 inducers ameliorates the associated inflammation, and that an HO-1 inhibitor exacerbates this inflammation.


METHODS
Forty four Lewis rats were given either 40 mol/kg hemin or 40 mol/kg SnPP (tin protoporphyrin IX) by intraperitoneal injection and twenty two uveitis control rats were injected with 0.5 mL of saline once daily 5-20 days after IRBP immunization inducing EAU. Three normal control rats were used for Western blotting and ELISA assay of HO-1. The clinical uveitis signs of inflammation were scored in the three groups from 0 to 4 on alternate three days. To confirm the clinical results, histological and immunohistochemical stain of HO-1 were performed on the day of peak inflammation and Western blotting and ELISA assay of HO-1 were performed on 6th, 12th and 18th day after IRBP immunization.


RESULTS
Hemin, an inducer of HO-1, ameliorated the clinical signs of EAU. In contrast, SnPP-treated rats show that the severity of the clinical sign were exacerbated at the peak period of the disease. These results are roughly compatible with histological, immunoblotting, and immunohistochemical evaluations and an ELISA assay of HO-1.


CONCLUSIONS
We suggest that HO-1 plays an important protective role in EAU.
Jang
Jeong Un
JU
Department of Ophthalmology, Wonkwang University, Icksan, Korea.
Lee
Sook Hee
SH
Choi
Chang Uk
CU
Bahk
Song-Chull
SC
Chung
Hun Taeg
HT
Yang
Yun Sik
YS
D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000187:drug effects; D006427:Hemin / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage*; D033401:Microscopy, Acoustic; D011524:Protoporphyrins / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D015866:Uveitis, Posterior / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D006427:Hemin; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1