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Jody A Summers, Elizabeth Martinez Cano; Visually Induced Changes in Choroidal Cytokine Production: Implications for Ocular Growth Regulation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3400.
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© ARVO (1962-2015); The Authors (2016-present)
Many studies have demonstrated the presence of a vision-dependent mechanism which acts to minimize refractive error through coordinated growth of the ocular tissues. Of great interest is the identification of the chemical signals that control ocular growth. Here we provide evidence that the pro-inflammatory cytokine, Interleukin-6 (Il-6), may play a pivotal role in the control of ocular growth.
Total RNA was isolated from choroids of treated and control eyes of chicks reared for 10 days with occluders to induce form deprivation myopia (FDM), followed by a recovery period of 45 minutes – 4 days. Additionally, RNA was isolated from 8 day old chicks treated with +15D and -15D lenses for 6 - 24 hrs as well as from normal chicks reared under various lighting conditions for 6 hrs. In some experiments, the nonspecific nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was administered via intravitreal injection (16.2 µmole in 30 ul 0.9% saline) upon recovery. Gene expression of Il-6, interleukin 1 beta (IL1B), interferon gamma (IFNG), and tumor necrosis factor alpha (TNF-α) were quantified using Taqman™ real time PCR and normalized to the housekeeping gene, GAPDH. Comparisons were made using paired and unpaired t-tests with significance at p ≤ 0.05.
Il-6 mRNA was significantly increased in choroids following 1.5 to 24 hrs of recovery compared to contralateral control eyes (↑99 - 1738%) and was significantly downregulated in treated choroids following 4 days of recovery (↓68%). IL1B mRNA was significantly increased following 6 hrs of recovery (↑101%). No significant differences were detected IFNG or TNF-α mRNA. Choroidal Il-6 gene expression was also significantly increased following +15D lens treatment for 24 hrs (↑277%). Administration of L-NAME (known to inhibit recovery) resulted in a significant decrease in Il-6 gene expression in treated eyes (↓71%). Choroidal Il-6 mRNA was significantly lower in eyes of chicks following 6 hrs of dark rearing, compared with chicks reared in normal room light (↓910%).
Il-6 gene expression is rapidly and transiently upregulated in choroids in response to myopic defocus, in a nitric oxide-dependent manner. Considering the pleiotropic nature of Il-6, these results suggest that Il-6 may mediate many aspects of the choroidal response for the control of ocular growth.
This is a 2020 ARVO Annual Meeting abstract.
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