The time course of changes in mRNA levels in tree shrew sclera during induced myopia and recovery.
OBJECTIVE
In tree shrews, visual form deprivation produces increased axial elongation of the deprived eye and a myopic shift in refractive state. A change in scleral extensibility (creep rate) is closely associated with the change in axial elongation rate. These effects may be due to scleral tissue remodeling produced by a change in scleral gene expression. In this study, the authors investigated the time course of changes in scleral mRNA levels for selected proteins during the development of form deprivation myopia and during recovery, to determine which, if any, are temporally associated with changes in scleral extensibility and axial elongation rate.


METHODS
Competitive RT-PCR was used to measure the levels of mRNA for structural proteins (collagen [alpha1(I) chain], decorin core protein), degradative enzymes (MMP-2 [gelatinase-A], MMP-3 [stromelysin-1]), and a tissue inhibitor of metalloproteinase (TIMP-1) in the scleras of tree shrews that had been subjected to 1, 2, 4, or 11 days of monocular form deprivation (MD) or 11 days of MD followed by 2 or 4 days of recovery produced by removal of the MD. Four groups of normal animals provided age-matched normal data.


RESULTS
Compared with the control eyes, deprived-eye MMP-2 mRNA levels were higher and MMP-3 levels were lower after 4 days of MD. Deprived-eye collagen mRNA levels were lower than control eye levels after 11 days of MD. The differential effects produced by MD were absent after 2 days of recovery and generally were reversed after 4 days. Decorin mRNA levels in the deprived and control eyes were not significantly different during either MD or recovery. During MD, mRNA levels for collagen, MMP-3, and TIMP-1 decreased in both the deprived and control eyes, compared with age-matched normal eyes. The binocular changes in collagen and TIMP-1 mRNA levels and the differential changes in MMP-2 and MMP-3 levels were detected at least as early as axial, refractive, and creep rate changes.


CONCLUSIONS
The up- and downregulation of the specific mRNAs studied, on a time course similar to that for physical changes in the sclera, suggests that modulation of gene expression by the visual environment may produce scleral remodeling and changes in scleral creep rate during the development of form deprivation myopia and recovery.
Siegwart
John T
JT
Department of Physiological Optics, School of Optometry, 302 Worrell Building, University of Alabama at Birmingham, Birmingham, AL 35294-4390, USA. siegwart@uab.edu
Norton
Thomas T
TT
D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D009216:Myopia / Q000378:metabolism* / Q000503:physiopathology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012590:Sclera / Q000378:metabolism*; D012683:Sensory Deprivation; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014418:Tupaiidae
D058575:Decorin; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2