Form-deprivation myopia induces activation of scleral matrix metalloproteinase-2 in tree shrew.
OBJECTIVE
To investigate whether structural changes to the sclera during form-deprivation myopia are caused by active tissue remodeling, the gelatinase activity of tree shrew scleras was studied in normal animals, form-vision deprived animals, and animals recovering from myopia.


METHODS
Infant tree shrews were monocularly deprived (MD) of form vision with translucent occluders for 5 days. Recovery animals were allowed 3 days of binocularly unoccluded vision after the period of form deprivation. Eyes were removed and dissected to provide scleral samples corresponding to equatorial and posterior regions. Gelatinase activity was assessed by quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE, gelatin, zymography of scleral matrix metalloproteinase (MMP) extracts.


RESULTS
The major gelatinolytic species present in tree shrew sclera was found to be MMP-2 (gelatinase A). In normal (nondeprived) animals, most of the MMP-2 was found to be in the latent form (the ratio of active-to-latent MMP-2 was 0.23 +/- 0.05 and 0.34 +/- 0.06 in equatorial and posterior samples, respectively; n = 10 eyes from five animals). After 5 days of MD, there was a threefold increase in the amount of active scleral MMP-2 in myopic eyes compared to contralateral control eyes, whereas latent MMP-2 activity levels were not altered significantly. This increase in active MMP-2 was seen in both the equatorial and posterior sclera of myopic eyes (active-to-latent MMP-2 ratios were 0.53 +/- 0.10 and 0.81 +/- 0.09 in equatorial and posterior regions, respectively; n = 6 animals). Contralateral control eyes had levels of both active and latent MMP-2 not significantly different from normal eyes. After only 3 days of unoccluded vision, previously deprived eyes that were now recovering from myopia had a fivefold lower level of active MMP-2 than that seen in deprived eyes after 5 days of MD. In fact, active (and latent) MMP-2 levels were reduced in recovering eyes even below the levels found in their contralateral control eyes. Active-to-latent ratios for recovering eyes were 0.11 +/- 0.03 and 0.15 +/- 0.03 in equatorial and posterior sclera, respectively (n = 5 animals).


CONCLUSIONS
These results demonstrate that form-deprivation myopia and recovery from myopia alter scleral catabolism and provide further support for the theory that changes in eye size during mammalian refractive development are the result of active tissue remodeling rather than passive scleral stretching alone.
Guggenheim
J A
JA
Department of Optometry and Vision Sciences, University of Wales, Cardiff, United Kingdom.
McBrien
N A
NA
D000818:Animals; D000831:Animals, Newborn; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005123:Eye / Q000201:enzymology / Q000473:pathology; D018093:Gelatinases / Q000032:analysis / Q000378:metabolism*; D006984:Hypertrophy / Q000201:enzymology; D008027:Light; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000032:analysis / Q000378:metabolism*; D009216:Myopia / Q000201:enzymology* / Q000209:etiology; D012590:Sclera / Q000737:chemistry / Q000201:enzymology*; D012683:Sensory Deprivation; D014418:Tupaiidae
D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2