Abstract
Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in “Circadian Rhythm Signaling” pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in “Calcium Signaling” (1 week) and “Glutamate Receptor Signaling” pathways (1 month). In contrast, dexamethasone (Dex) affected the “GABA Receptor Signaling” (1 week) and “Serotonin Receptor Signaling” (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.
Highlights
Intravitreal injections of dexamethasone (Dex) and triamcinolone (TAA) are a mainstay in a clinical retinal practice to treat a wide range of pathologies, such as cystoid macular edema secondary to retinal vein occlusion, diabetic macular edema, choroidal neovascularization in macular degeneration, and noninfectious uveitis [1,2,3,4,5,6]
1.93 1.66 −1.35 11.9 1.41 15.18 TAA/1 wk (Taq) 3.07 1.25 0.43 39.19 1.87 11.52 Dex/1 mo (Taq) −1.93 9.3 −1.77 TAA/1 mo (Taq) −1.41 0.34 −0.31 a role in many ocular disorders including age-related macular degeneration, central serous chorioretinopathy, whitedot syndromes, and retinitis pigmentosa, which can lead to permanent visual distortion and blindness
This process has been shown to be under circadian clock control [26,27,28]
Summary
Intravitreal injections of dexamethasone (Dex) and triamcinolone (TAA) are a mainstay in a clinical retinal practice to treat a wide range of pathologies, such as cystoid macular edema secondary to retinal vein occlusion, diabetic macular edema, choroidal neovascularization in macular degeneration, and noninfectious uveitis [1,2,3,4,5,6] These pathologies affect the retina and involve the RPE and choroid. In a previous study using a mouse model, we demonstrated that intravitreal steroids affect the expression of several genetic pathways and alter the balance between neuroprotective and neurodegenerative processes in retina [9] In this sequel study we used the same model to examine the differential gene expression effects of intravitreal injections of Dex and TAA in RPE/choroid tissue in vivo, since they too are affected by both disease pathogenesis and intravitreal steroidal treatment at clinically relevant time points of 1 week and 1 month postinjection. The purpose of this study was to evaluate the gene expression effects that intravitreal Dex and TAA have on the RPE/choroid and the differences between them at clinically relevant time points
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