Biomedical subjects

John T Siegwart

Publications and source records attributed to John T Siegwart.

5 recordsLinked to original sources

PubMed2006

Effectiveness of hyperopic defocus, minimal defocus, or myopic defocus in competition with a myopiagenic stimulus in tree shrew eyes.

PURPOSE: To examine the ability of hyperopic defocus, minimal defocus, and myopic defocus to compete against a myopiagenic -5-D lens in juvenile tree shrew eyes. METHODS: Juvenile tree shrews (n > or = 5 per group), on a 14-hour lights-on/10-hour lights-off schedule, wore a monocular -5-D lens (a myopiagenic stimulus) over the right eye in their home cages for more than 23 hours per day for 11 days. For 45 minutes each day, the animals were restrained so that all visual stimuli were >1 m away. While viewing distance was controlled, the -5-D lens was removed and another lens was substituted with one of the following spherical powers: -5 D, -3 D (hyperopic defocus); plano (minimal defocus); or +3, +4, +5, +6, or +10 D (myopic defocus). Daily noncycloplegic autorefractor measures were made on most animals. After 11 days of treatment, cycloplegic refractive state and axial component dimensions were measured. RESULTS: Eyes with the substituted -5- or -3-D-lens developed significant myopia (mean +/- SEM, -4.7 +/- 0.3 and -3.1 +/- 0.1 D, respectively) and appropriate vitreous chamber elongation. All animals with the substituted plano lens (minimal defocus) during the 45-minute period showed no axial elongation or myopia (the plano lens competed effectively against the -5-D lens). Variable results were found among animals that wore a plus lens (myopic defocus). In 11 of 20 eyes, a +3-, +4-, or +5-D lens competed effectively against the -5-D lens (treated eye <1.5 D myopic relative to its fellow control eye). In the other eyes (9/20) myopic defocus was ineffective in blocking compensation; the treated eye became more than 2.5 D myopic relative to the control eye. The +6- and +10-D substituted lenses were ineffective in blocking compensation in all cases. CONCLUSIONS: When viewing distance was limited to objects >1 m away, viewing through a plano lens for 45 minutes (minimal defocus) consistently prevented the development of axial elongation and myopia in response to a myopiagenic -5-D lens. Myopic defocus prevented compensation in some but not all animals. Thus, myopic defocus is encoded by at least some tree shrew retinas as being different from hyperopic defocus, and myopic defocus can sometimes counteract the myopiagenic effect of the -5-D lens (hyperopic defocus). However, it appears that minimal defocus is a more consistent, strong antidote to a myopiagenic stimulus in this mammal closely related to primates.

Animals↗

PubMed2006

Darkness causes myopia in visually experienced tree shrews.

PURPOSE: To examine the effect of a period of continuous darkness on the refractive state and vitreous chamber depth of normal light-reared juvenile tree shrew eyes, and to learn whether eyes that developed myopia in response to monocular minus-lens wear will recover in darkness. METHODS: Starting at 16 days of visual experience (VE), the refractive state of five dark-treatment tree shrews was measured daily to confirm that it was stable and nearly emmetropic. After corneal and ocular component dimension measures, the animals were placed into continuous darkness for 10 days. On removal of the animals from darkness, corneal and ocular component measures were repeated, and daily refractive measures were resumed. The refractive state of the dark-treatment group was compared with that of a normal-lighting group (n = 5) that received standard colony lighting throughout the measurement period. Five dark-recovery animals wore a monocular -5-D lens for 11 days to induce myopia before they were placed into continuous darkness for 10 days. RESULTS: The animals in the normal-lighting group completed the emmetropization process, stabilizing at approximately (mean +/- SEM) 0.7 +/- 0.3 D of hyperopia (noncycloplegic refraction, corrected for the small eye artifact) at 60 days of VE. Dark-treatment group eyes shifted toward myopia (mean +/- SEM, -4.3 +/- 0.5 D) in the dark. The vitreous chamber became elongated by 0.09 +/- 0.02 mm relative to normal eyes. Corneal power showed a small, near-normal decrease (1.4 +/- 0.3 D). Four of five myopic eyes in the dark-recovery group became more myopic (-2.2 +/- 0.9D) in darkness, and all the fellow control eyes shifted toward myopia (-2.8 +/- 0.5 D). CONCLUSIONS: Maintaining emmetropia is an active process. After eyes have achieved emmetropia or have compensated for a minus lens, continued visual guidance is necessary to maintain a match between the axial length and the focal plane or for recovery to occur. Absence of light is myopiagenic in tree shrews that have developed with normal diurnal lighting. This result contrasts with the apparent absence of a darkness effect in tree shrews reared in the dark from before normal eye opening.

Animals↗

PubMed2005

Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery.

PURPOSE: In juvenile tree shrews, a minus-power lens placed in front of the eye produces increased axial elongation and a myopic shift in refractive state that compensates for the power of the lens. Scleral tissue remodeling and modulation of the mechanical properties of the sclera occur during lens compensation. In this study, the time course of changes in scleral mRNA levels of three MMPs and three TIMPs during compensation for a minus lens and during recovery was investigated, to determine which, if any, are temporally associated with changes in the mechanical properties of the sclera and the axial elongation rate. METHODS: Competitive RT-PCR was used to measure the levels of mRNA for MT1-MMP, MMP-2, MMP-3, TIMP-1, TIMP-2, and TIMP-3 in the scleras of tree shrews that had received either 1, 2, 4, or 11 days of monocular -5-D lens treatment, or 11 days of -5-D lens treatment followed by 2 or 4 days of recovery. RESULTS: Relative to their control eyes, treated eye MT1-MMP and MMP-2 mRNA levels were significantly higher, and TIMP-3 levels were lower by 1 to 4 days of minus lens treatment. These differential effects were absent by 11 days of treatment when the treated eyes had compensated for the lens. The levels of all three TIMPs spiked upward in both eyes after 2 days of recovery. The differential changes in MT1-MMP, MMP-2, and TIMP-3 mRNA levels were all restricted to the treated eye and were temporally associated with the differential changes in axial elongation, refractive state, and the previously measured changes in creep rate. CONCLUSIONS: The observed changes in MT1-MMP, MMP-2, TIMP-2, and TIMP-3 mRNA are consistent with visually modulated MT1-MMP activation of MMP-2 and with MT1-MMP degradation of scleral extracellular matrix components. These data constitute further evidence that visual signals modulate gene expression of selected MMPs and TIMPs to control scleral remodeling, the mechanical properties of the sclera, axial elongation, and refractive state.

Animals↗

PubMed2003

Refractive state of tree shrew eyes measured with cortical visual evoked potentials.

PURPOSE: To determine the refractive state of tree shrew eyes using visual evoked potentials (VEP's) recorded from primary visual cortex and compare the values with those obtained with streak retinoscopy and with an autorefractor. METHODS: VEP's were recorded in seven normal tree shrews and three animals in which approximately 5 D of myopia (relative to control eye) was induced by monocular -5 D lens wear. While the animals were awake, refractive correction was measured with an autorefractor before and after cycloplegia (1% atropine and 2.5% phenylepherine). When anesthetized, cycloplegic refractive correction was measured with streak retinoscopy. Then VEP's were produced with square-wave counterphased (1 Hz) high-contrast checkerboard patterns near the animals' high spatial frequency cutoff. Spherical lenses (2 D steps) were placed before the eye, and the VEP (average of 128 sweeps) was measured to determine the lens that produced the largest first positive peak (P1). RESULTS: VEP's were obtained over a broad range of trial lenses. Tuning was narrower when check sizes were small. In normal and control eyes, the P1 amplitude was largest, on average, for a trial lens of (mean +/- SD) -0.6 +/- 1.6 D (corrected for working distance but not vertex distance). The mean streak retinoscopy value (spherical equivalent at the corneal plane) was 7.0 +/- 0.8 D, and mean autorefractor values were 4.0 +/- 1.1 D (cycloplegic) and 3.7 +/- 1.2 D (noncycloplegic). In the eyes that compensated for a -5 D lens, the largest P1 values occurred with lenses with a power of -6.3 +/- 3.2 D. Thus, the VEP measure showed a similar treated vs. control eye difference as did streak retinoscopy (treated eyes, 4.7 +/- 0.4 D myopic) and the autorefractor (treated eyes, 4.8 +/- 0.5 D myopic). CONCLUSIONS: Normal tree shrew eyes are approximately emmetropic. The hyperopic values obtained with streak retinoscopy and the autorefractor are consistent with the presence of a "small-eye artifact" in tree shrews. Eyes that have compensated for a -5 D lens are myopic by approximately the value of the lens.

Animals↗

PubMed2002

The time course of changes in mRNA levels in tree shrew sclera during induced myopia and recovery.

PURPOSE: 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.

Animals↗