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Andrei V Tkatchenko, David Troilo, Alexandra Benavente-Perez, Tatiana V Tkatchenko; Retinal gene expression profiling following exposure to hyperopic or myopic defocus supports retina’s capacity to recognize sign of defocus. Invest. Ophthalmol. Vis. Sci. 2018;59(9):751.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies suggest that the eye can compensate for both myopic and hyperopic defocus. However, the ability of the retina to recognize the sign of defocus has been a subject of much controversy. The molecular mechanisms underlying sign-of-defocus-specific ocular response are unknown. The purpose of this study was to determine if retinal gene expression is affected by the sign of defocus, and how it might relate to the sign-of-defocus-specific eye growth responses during emmetropization.
Four groups of marmosets (3 animals each), were treated with -5D or +5D lenses, which were applied to the right eye for 10 days or 5 weeks. The left eye was fitted with a control plano lens. Following lens treatment, retinae were harvested and used to perform whole-genome gene expression profiling using RNA-seq.
A total of 119 genes were differentially expressed between -5D-treated eyes and the contralateral plano control eyes after 10 days of treatment, 309 genes were differentially expressed between -5D-treated eyes and control eyes after 5 weeks of treatment. In +5D-treated eyes compared to controls, 79 genes were differentially expressed after 10 days, and 740 genes were differentially expressed after 5 weeks of treatment. Comparison of differential genes from the four experimental groups revealed that each experimental condition leads to differential expression of a unique set of genes with very little overlap between the conditions. Additional analyses revealed that there was very little overlap between the pathways underlying retinal response to -5D and +5D lenses, and almost complete transition from one set of pathways to another between 10 days of treatment and 5 weeks of treatment for both -5D and +5D experimental groups.
Our data support the hypothesis that the retina can distinguish between hyperopic and myopic defocus, and that emmetropization is regulated through a distinct bidirectional retinal signaling mechanism sensitive to the sign of defocus, which we propose calling Bidirectional Emmetropization by the Sign of Optical Defocus (BESOD). The signaling mechanism has at least two stages revealed by the transition from one set of genes to another between 10 days and 5 weeks of exposure to defocus. These findings may help develop new treatments to slow, or possibly even stop, the development of myopia.
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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