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jinglei yang; Declines in FP receptor-linked signaling may contribute to form-deprived myopic development in guinea pigs. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3614.
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© ARVO (1962-2015); The Authors (2016-present)
Metabonomics, which quantifies the numerous metabolites that make up the metabolome of a given cell or tissue, provides an additional benefit in that it directly reads out of the physiological state of a cell or tissue at a given point in time. Here we applied gas chromatography-time of flight mass spectrum (GC-TOF) analysis to explore the retinal metabolic profile of form-deprived myopic guinea pigs at different time points in the hope of providing key information about metabolic changes contributing to myopia development.
Retinal metabolite profiles were obtained using GC-TOF from guinea pigs including controls, 3 days and 2 weeks after form deprivation. Multidementional PLS-DA models were used to discriminate retinal profiles in form-deprived and normal guinea pigs and identify important metabolites in pathways contributing to myopia development. To determine whether alterations in metabolic pathways involving arachidonic acid (ARA, C20:4) are associated with refractive development, an prostaglandin F receptor(FP)agonist latanoprost and an antagonist AL8810 were injected into the sub-bulbar conjunctival space under local surface anesthesia. All injections were executed under dim red light in the right eye once daily (at 9:00 AM ) for four weeks growing in mormal visional environment or two weeks under form deprivation.
The displacement between the form deprived samples and normal controls was associated with the degree of myopia development. Octadecanoic acid(C18:0), octadecenoic acid(C18:1), ARA and DHA were at lower levels in retinas from guinea pigs 3 days and 2 weeks after form deprivation compared with controls, suggesting downregulation of ARA associated metabolic pathways during myopia development. Latanoprost-induced FP receptor activation had no effect on normal refraction development but inhibited FDM. Inhibition of FP receptors by AL8810 induced more myopia in both a normal visual and form deprivation environment.
ARA biosynthesis is downregulated during myopia development, which is consistent with the effects of a FP receptor agonist and antagonist. It is thus proposed that retinal PGF levels and FP receptor signalling pathway undergo downregulation during myopia development, which may be key to myopia mechanisms. These findings suggest that metabonomics is an effective tool to get insights into myopia onset.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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