Abstract
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Keywords: 511 emmetropization •
688 retina •
701 retinal pigment epithelium