Effects of growth hormone releasing hormone receptor antagonist in experimental autoimmune intraocular inflammation
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AbstractPurpose
Steroid, which possesses several adverse effects, remains the standard treatment of autoimmune uveitis. Thus, alternative effective treatments are desirable. The growth hormone-releasing hormone (GHRH) pathway exerts regulatory effects on several inflammatory diseases including uveitis. We investigated the anti-inflammatory effects of GHRH-receptor (GHRHR) peptides on experimental autoimmune uveoretinitis (EAU) mice.

Methods
EAU was induced in 6-week old female C57BL/6J mice with subcutaneous injection of 300 μg human interphotoreceptor retinoid-binding protein peptide 1-20 per mouse by following a published protocol. 6 mice were used in each group. Controls were mock induced with PBS. 14 days after EAU induction, 10 μg GHRHR agonist MR-409, 10 μg GHRHR antagonist MIA-602 or 0.2% DMSO treatment was injected into each mouse subcutaneously daily for 7 days. Mice were monitored in cSLO fundus photos. Inflammatory manifestations in the posterior segment were quantified by using a published scoring system. Relative photopic and scotopic b-wave ERG amplitudes were calculated as day21 amplitude divided by that on day0 after EAU induction under photopic and scotopic stimuli (30 and 10 cd.s/m2 respectively). Mann-Whitney U test was used to compare the medians of two groups. All statistical tests were two-tailed and were performed using a significance level of P = 0.05.

Results
Retinal vasculitis and infiltrating cells in the vitreous were seen after EAU induction. These features were less severe in MIA-602 treated mice. The clinical score reduced significantly (0.29 ± 0.25, P < 0.05) in EAU mice treated with MIA-602, compared to that treated with DMSO (0.81 ± 0.12). No reduction was seen in MR-409 treated EAU mice (0.63 ± 0.23), which was comparable to EAU mice treated with DMSO (P = 0.51). No significant difference was seen in relative photopic ERG in MR-409-treated (0.84 ± 0.04), MIA-602 treated (0.81 ± 0.05) and DMSO treated (0.71 ± 0.10) EAU mice (P > 0.05) . Significant improvement was seen in relative scotopic ERG by MIA-602 treatment (0.98 ± 0.05) compared to DMSO for EAU (0.76 ± 0.05, P < 0.01). No significant difference was seen in relative scotopic ERG in MR-409-treated EAU mice (0.81 ± 0.02) compared to DMSO treated EAU mice (P > 0.05).

Conclusions
Our findings show GHRHR antagonist is a potent anti-inflammatory agent against inflammation of autoimmune uveitis.
All Author(s) ListChu WK, Li J, He J, Yip W, Guo L, Wong O, Pang CC
Name of ConferenceThe Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) 2019
Start Date of Conference28/04/2019
End Date of Conference02/05/2019
Place of ConferenceVancouver, British Columbia
Country/Region of ConferenceCanada
Proceedings TitleINVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Year2019
Volume Number60
Issue Number9
ISSN0146-0404
LanguagesEnglish-United Kingdom

Last updated on 2020-25-09 at 03:34