Abstract
Purpose: :
To compare early mRNA expression patterns for scleral extracellular matrix and signaling proteins after 1 day of minus lens wear or 1 day of recovery with patterns after 4 days of lens wear and 4 days of recovery.
Methods: :
Three groups of tree shrews (n=8 each) wore a monocular -5 D lens starting 24 days after normal eye opening (days of VE). The fellow eye served as a control. One group (LIM-1) wore a -5D lens for 1 day. A second group (REC-1) wore a -5D lens for 11 days, compensated fully and were measured after 1 day of recovery with no lens. A third group (COMP) wore a -5D lens for 11 days. These groups were compared with previously reported (Gao et al, ARVO, 2008) normals measured at 24 and 38 days of VE and with LIM and REC groups that were measured after 4 days of lens wear or 4 days of recovery. Real-time PCR was used to assess mRNA levels for 27 genes.
Results: :
Differential changes: After one day of lens wear (LIM-1), only mRNA for ADAMTS1, an aggrecanase, was differentially expressed (higher in treated eye). After 4 days of -5D lens wear, treated eye mRNA levels for TGFβR3, TGFBI (big-h3) & MT1-MMP were higher and TGFβ1, TGFβ2, THSB1, TNC, SPARC, SPP1, TIMP3 & ADAMTS5 were lower compared to the control eyes. After 11 days of lens wear (COMP) there was no differential expression. In contrast, after 1 day of recovery (REC-1), the mRNA levels for TGFβ2, TGFβR1, 2 and 3, FGF2, SPARC, SDC4, ADAMTS1 & 5 & COL6A1 were differentially lower in the recovering eyes. After 4 days of recovery, the pattern had changed, so that TGFβ1, 2 & 3, THBS2 & TIMP3 were differentially higher in the recovering-eyes. Interestingly, there was a general pattern of downregulation in both the treated and control eye after 1 day of -5D lens and after 1 day of recovery (LIM-1 vs 24N: treated and control, 25 of 27 genes; REC-1 vs COMP: treated 25 of 27, control 24 of 27; significant by sign test).
Conclusions: :
Retinal "go" signals (produced by wearing a -5D lens) in a normal eye produce differential mRNA changes in the sclera more slowly than do retinal "stop" signals (recovery) in an elongated, myopic eye. This pattern is similar to changes in scleral creep rate where there is not a differential response to 1 day of -5D lens but is a strong differential response (decrease in creep rate) to 1 day of recovery. The initial pattern of downregulation in both the treated and control eyes suggests: 1) that there were rapid control-eye effects and 2) that a similar, early, yoked response (downregulation) to both the "go" and the "stop" signals underlies the various differential responses.
Keywords: myopia • sclera • gene/expression