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Li He, Michael R Frost, Thomas T Norton; Differential gene expression in tree shrew retina compared with retinal pigment epithelium (RPE) in response to six hours of minus-lens wear. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3037.
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Extensive evidence suggests local regulation of ocular growth. The retina initiates signals that regulate this growth and RPE is an important transmitter/translator of those signals. We examined and compared early gene expression patterns in the retina vs. RPE from eyes of the same experimental animals responding to short-term minus-lens wear.
Starting 24 days after normal eye opening, a group of seven tree shrews wore a monocular −5 D lens for six hours to initiate increased axial elongation and the development of lens-induced myopia. The untreated contralateral eye served as a control. Quantitative real-time PCR was used to measure gene expression in retina and RPE tissues separately. Forty-four genes of interest were chosen based on the literature and preliminary studies in this lab.
RNA yields were typically around 20 µg from the retina and 2 µg from the RPE. After six hours of minus-lens wear, significant differential mRNA expression changes (treated vs. control) were found for four genes in the retina: BMP2, CTGF, and EGR1 were down-regulated, whilst SST was up-regulated. In the RPE, eleven genes showed significant differential expression: GJA1, IGF2R, and LRP2 were up-regulated, whilst APOE, DRD1, NOS1, OPN4, PENK, SLC18A2, SSTR2, and VIP were down-regulated. No gene was differentially expressed in both tissues. These relatively small expression changes, typically <2-fold, are induced prior to measurable changes in refraction or axial length.
Six hours of minus-lens wear is sufficient to produce differential gene expression in tree shrew retina and in RPE. The pattern of gene expression differs between the two, suggesting that emmetropization-related signaling is transformed as it moves from retina to RPE. Expression changes in some of these genes have been reported in chick retina/RPE, analyzed together, after 6 hours of minus-lens wear (Stone et al. IOVS 2011; 52:5765-5777). Our tree shrew results suggest that some of these changes occur in retina and some in RPE, suggesting that each ‘compartment’ in the emmetropization signaling cascade should be analyzed separately.
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