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WAI KIT CHU, Jian Li, Jing Na He, Wong Ying Yip, Liutao Guo, Oi Man Mandy Wong, Calvin C P Pang; Effects of growth hormone-releasing hormone receptor antagonist in experimental autoimmune intraocular inflammation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):789.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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).
Our findings show GHRHR antagonist is a potent anti-inflammatory agent against inflammation of autoimmune uveitis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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