Abstract
Purpose: :
Although the STOP visual stimulus is similar, recovery from minus-lens wear (REC) produces a greater refractive change than plus-lens wear (PLW) in juvenile tree shrews (Siegwart & Norton, Exp. Eye Res., 2010). Because the sclera controls axial elongation and refractive error, we compared gene expression signatures in the sclera produced by REC and PLW in order to learn more about the mechanisms underlying the differing refractive responses.
Methods: :
Four groups of tree shrews (n=7 per group) wore a monocular –5 D lens for 11 days from 24 to 35 days of visual experience (VE), and then recovered (lens removed) for 0 hr, 2 hr, 1 day, or 4 days. Three age-matched groups (n=7 per group) wore a +5 D lens for 2 hr, 1 day, or 4 days. A normal group was examined at 38 days of VE. We examined 44 candidate genes which included transcriptional regulators (tr), signaling molecules (sm), chaperones (c), matricellular proteins (mc), metalloproteinases and their inhibitors (mt), cell adhesion proteins (ca), and extracellular matrix proteins (em). The mRNA expression levels for these genes, normalized to POLR2A, were assessed with quantitative real-time PCR.
Results: :
There was little refractive or differential gene expression response after 1 day of REC or PLW. After 4 days, the refractive change in REC was 2.6 ± 0.4 D vs. 0.6 ± 0.3 D for PLW (mean ± SEM difference [treated - control eyes]). By 4 days, gene expression was generally up-regulated in both conditions; 24 genes showed significant regulation in one or both conditions. CTGF(mc), TIMP3(mt), ANXA2(ca), CAPNS1(ca), and ACAN(em) were up-regulated in both. TGFB1(sm), WISP1(mc), NOV(mc), TIMP1(mt), and COL1A1(em) were up-regulated in REC but not PLW. TGFB2(sm), FGFR2(sm), SERPINH1(c), CYR61(mc), MMP14(mt), TIMP2(mt), ANAXA1(ca), FMOD(em), OGN(em), and COL12A1(em) were up-regulated in PLW but not REC. TGFBR3(sm), IGF1(sm), and NYX(em) were down-regulated in REC but not PLW. ADAMTS5(mt) was down-regulated in PLW but not REC.
Conclusions: :
REC produced a greater refractive change than PLW. The scleral gene expression response to PLW differed somewhat in the specific genes affected but was similar in overall direction and amount to REC. Therefore, the minimal refractive response to PLW does not appear to be due to a lack of scleral fibroblast response to the STOP visual stimulus. Rather, it may reflect a different effect of the gene expression products on the scleral extracellular matrix of normal (PLW) vs. elongated (REC) sclera.