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Christian Uenseok Kim, Ornella Adeyanju Oluwole, Menaka Thounaojam, Pamela M Martin, Diana Gutsaeva, Manuela Bartoli; Neuroprotective effects of GHRH analogs in traumatic optic neuropathy involve antioxidant and anti-inflammatory activities. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2492. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Traumatic optic neuritis (TON) is a potentially blinding condition occurring as consequence of direct or indirect traumatic impact. We have previously shown that agonistic analogs of the hypothalamic hormone growth hormone releasing hormone (GHRH) exert neuroprotective effects in an experimental model of TON. Here we have further characterized the protective effects of GHRH analogs by assessing their antioxidant and anti-inflammatory activities.
Experiments were conducted using a mouse model of optic nerve crush (ONC). GHRH agonistic analog MR-409 (15micrograms/Kg) was administered subcutaneously every day post-injury until sacrifice (7 days). Hydroethidine (DHE) staining was used to probe superoxide levels. Immunohistochemistry and immunoblotting were used to assess retinal distribution and levels of oxidative and nitrative stress markers such as 4-hydroxynonenal (4-HNE) and nitrotyrosine (3-NT). Quantitative PCR and multiplex ELISA assays were conducted to measure mRNA and protein levels (respectively) of interleukin 6 (IL-6), interleukin 1beta (IL1-beta), tumor necrosis alpha (TNF-alpha) in retinal extracts. Same cytokines were also measured by ELISA in plasma.
ONC stimulated superoxide production, as evidenced by increased DHE staining at retinal and optic nerve levels. Treatment of the ONC mice with the GHRH agonistic analog MR-409 reduced the DHE signal. Increased levels of 4-HNE and 3-NT were measured in ONC mice whereas treatment with MR-409 significantly decreased (p<0.05, n=6) these oxidative and nitrative stress markers. Finally, qPCR and ELISA assays showed increased retinal and plasma levels of IL-6, IL-1beta and TNF-alpha. These cytokines were reduced to control levels by treatments of the ONC mice with MR-409.
Our studies further support the significant neuroprotective effects of GHRH agonistic analog in TON by a mechanism involving GHRH anti-oxidant and anti-inflammatory properties.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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