Project description:Ocular growth is regulated locally by signals produced in the retina that ultimately act on the growth of the scleral tissue. Consequently, a number of studies have investigated changes in retinal gene expression during manipulation of ocular growth in an attempt to elucidate the biochemical pathways underlying eye growth. However, due to the highly heterogenous nature of the retina, important changes in gene expression can be masked. Therefore, this study has investigated changes in gene expression specifically within the retinal amacrine cell layer, the most likely generator of growth signals, during manipulations of ocular growth. Chicks were monocularly treated with either -7D (n=3, growth stimulant) or +7D (n=3, growth suppressant) lenses for 24hrs, with untreated age-matched chicks serving as a control (n=3). Total RNA from the amacrine cell layer was isolated from laser-capture microdissected (Zeiss, Bernried, Germany) 10µm thick sections. Labeled cRNA was prepared from three separate samples per condition and hybridized to Affymetrix GeneChip Chicken Genome arrays.
Project description:During postnatal development, the optical geometry of the eye is refined through a process called emmetropization. During eye emmetropization, positive optical defocus inhibits eye growth whereas negative optical defocus accelerates it. Increased exposure to negative optical defocus leads to the development of myopia. Although several studies investigated gene regulatory networks underlying retinal response to optical defocus, temporal changes that occur during ocular response to optical defocus are poorly understood. Here, we performed a genome-wide analysis of the retinal gene regulatory networks underlying optical-defocus-induced myopia using massive parallel RNA sequencing (RNA-seq) in chickens exposed to negative optical defocus for 1, 3 and 6 days. Our analysis revealed large-scale dynamic temporal changes in the retinal signaling pathways involved in the eye’s response to negative optical defocus. We found that different sets of pathways and biological functions were involved in the early, sustained and delayed response to optical defocus causing myopia. These data refine signaling pathways that can be targeted for myopia control and provide a framework for the development of new treatment options for myopia.
Project description:During postnatal development, the optical geometry of the eye is refined through a process called emmetropization. During eye emmetropization, positive optical defocus inhibits eye growth whereas negative optical defocus accelerates it. Increased exposure to negative optical defocus leads to the development of myopia. Although several studies investigated gene regulatory networks underlying retinal response to optical defocus, temporal changes that occur during ocular response to optical defocus are poorly understood. Here, we performed a genome-wide analysis of the retinal gene regulatory networks underlying optical-defocus-induced myopia using massive parallel RNA sequencing (RNA-seq) in chickens exposed to negative optical defocus for 1, 3 and 6 days. Our analysis revealed large-scale dynamic temporal changes in the retinal signaling pathways involved in the eye’s response to negative optical defocus. We found that different sets of pathways and biological functions were involved in the early, sustained and delayed response to optical defocus causing myopia. These data refine signaling pathways that can be targeted for myopia control and provide a framework for the development of new treatment options for myopia.
Project description:During postnatal development, the optical geometry of the eye is refined through a process called emmetropization. During eye emmetropization, positive optical defocus inhibits eye growth whereas negative optical defocus accelerates it. Increased exposure to negative optical defocus leads to the development of myopia. Although several studies investigated gene regulatory networks underlying retinal response to optical defocus, temporal changes that occur during ocular response to optical defocus are poorly understood. Here, we performed a genome-wide analysis of the retinal gene regulatory networks underlying optical-defocus-induced myopia using massive parallel RNA sequencing (RNA-seq) in chickens exposed to negative optical defocus for 1, 3 and 6 days. Our analysis revealed large-scale dynamic temporal changes in the retinal signaling pathways involved in the eye’s response to negative optical defocus. We found that different sets of pathways and biological functions were involved in the early, sustained and delayed response to optical defocus causing myopia. These data refine signaling pathways that can be targeted for myopia control and provide a framework for the development of new treatment options for myopia.
Project description:During postnatal development, the optical geometry of the eye is refined through a process called emmetropization. During eye emmetropization, positive optical defocus inhibits eye growth whereas negative optical defocus accelerates it. Increased exposure to negative optical defocus leads to the development of myopia. Although several studies investigated gene regulatory networks underlying retinal response to optical defocus, temporal changes that occur during ocular response to optical defocus are poorly understood. Here, we performed a genome-wide analysis of the retinal gene regulatory networks underlying optical-defocus-induced myopia using massive parallel RNA sequencing (RNA-seq) in chickens exposed to negative optical defocus for 1, 3 and 6 days. Our analysis revealed large-scale dynamic temporal changes in the retinal signaling pathways involved in the eye’s response to negative optical defocus. We found that different sets of pathways and biological functions were involved in the early, sustained and delayed response to optical defocus causing myopia. These data refine signaling pathways that can be targeted for myopia control and provide a framework for the development of new treatment options for myopia.
Project description:During postnatal development, the optical geometry of the eye is refined through a process called emmetropization. During eye emmetropization, positive optical defocus inhibits eye growth whereas negative optical defocus accelerates it. Increased exposure to negative optical defocus leads to the development of myopia. Although several studies investigated gene regulatory networks underlying retinal response to optical defocus, temporal changes that occur during ocular response to optical defocus are poorly understood. Here, we performed a genome-wide analysis of the retinal gene regulatory networks underlying optical-defocus-induced myopia using massive parallel RNA sequencing (RNA-seq) in chickens exposed to negative optical defocus for 1, 3 and 6 days. Our analysis revealed large-scale dynamic temporal changes in the retinal signaling pathways involved in the eye’s response to negative optical defocus. We found that different sets of pathways and biological functions were involved in the early, sustained and delayed response to optical defocus causing myopia. These data refine signaling pathways that can be targeted for myopia control and provide a framework for the development of new treatment options for myopia.
Project description:In chicks, the avian homologue of the early growth response protein-1 (ZENK) has been shown to be increased in a special cell type of the retina, the glucagonergic amacrine cells, under conditions that lead to a reduction in eye growth (myopic defocus, recovery of myopia) and decreased under conditions that enhance ocular growth (hyperopic defocus, form-deprivation). The investigation of Egr-1 knock-out mice showed that homozygous knock-out mice with no functional Egr-1 protein developed relative axial myopia at the age of 42 and 56 days, compared to heterozygous- and wildtype Egr-1 knock-out mice. To clarify the role of Egr-1 in the retinal regulation of eye growth, and to get an idea about the biochemical pathways underlying this mechanism, we studied the role of Egr-1 in more detail using Affymetrix microarrays. Experiment Overall Design: Retinal samples of young homozygous Egr-1 knock-out and wildtype mice at the age of 30 days (hm30 and wt30; no difference in axial eye length yet) and 42 days (hm42 and wt42; already a difference in axial eye length of 59 µm) were taken to compare the mRNA expression changes over time between these two genotypes and within the same genotype between the two age groups.
Project description:Refractive eye development is regulated by optical defocus in a process of emmetropization. Excessive exposure to negative optical defocus often leads to the development of myopia. However, it is still largely unknown how optical defocus is detected by the retina. Here, we used genome-wide RNA-sequencing (RNA-seq) to conduct analysis of the retinal genetic networks underlying contrast perception and refractive eye development. We report that the genetic network subserving contrast perception plays an important role in optical defocus detection and emmetropization. Our results demonstrate an interaction between contrast perception, the retinal circadian clock pathway and the signaling pathway underlying optical defocus detection. We also observe that the relative majority of genes causing human myopia are involved in the processing of optical defocus. Together, our results support the hypothesis that optical defocus is perceived by the retina using contrast as a proxy and provide new insights into molecular signaling underlying refractive eye development.