Gene expression signatures in tree shrew sclera during recovery from minus-lens wear and during plus-lens wear.

Purpose: In juvenile tree shrews that have developed minus lens-induced myopia, if lens treatment is discontinued, refractive recovery (REC) occurs. However, in age-matched juvenile animals, plus-lens wear (PLW) produces little refractive change, although the visual stimulus (myopia) is similar (an "IGNORE" response). Because the sclera controls axial elongation and refractive error, we examined gene expression in the sclera produced by PLW and compared it with the gene expression signature produced by REC to learn whether these similar refractive conditions produce similar, or differing, scleral responses.

A Novel Tree Shrew (Tupaia belangeri) Model of Glaucoma.

Purpose: Primates and rodents are used widely as animal models of glaucoma, but each has significant limitations. Researchers need additional animal models that closely resemble the relevant anatomy and pathologic features of the human disease to more quickly advance research. We validate a novel glaucoma animal model in tree shrews (Tupaia belangeri).

Altered gene expression in tree shrew retina and retinal pigment epithelium produced by short periods of minus-lens wear.

Hyperopic refractive error is detected by retinal neurons, which generate GO signals through a direct emmetropization signaling cascade: retinal pigment epithelium (RPE) into choroid and then into sclera, thereby increasing axial elongation. To examine signaling early in this cascade, we measured gene expression in the retina and RPE after short exposure to hyperopia produced by minus-lens wear. Gene expression in each tissue was compared with gene expression in combined retina + RPE.

Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews.

We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control.

The wavelength composition and temporal modulation of ambient lighting strongly affect refractive development in young tree shrews.

Shortly after birth, the eyes of most animals (including humans) are hyperopic because the short axial length places the retina in front of the focal plane. During postnatal development, an emmetropization mechanism uses cues related to refractive error to modulate the growth of the eye, moving the retina toward the focal plane. One possible cue may be longitudinal chromatic aberration (LCA), to signal if eyes are getting too long (long [red] wavelengths in better focus than short [blue]) or too short (short wavelengths in better focus).

The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews.

lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period.

Changing material properties of the tree shrew sclera during minus lens compensation and recovery.

Purpose: To estimate two collagen-specific material properties (crimp angle and elastic modulus of collagen fibrils) of the remodeling tree shrew sclera during monocular -5 diopter (D) lens wear and recovery.

Methods: Tensile tests were performed on scleral strips obtained from juvenile tree shrews exposed to three different visual conditions: normal, monocular -5 D lens wear to induce myopia, and recovery. Collagen fibrils are crimped in the unloaded sclera and uncrimp as the tissue stiffens under load.

Scleral gene expression during recovery from myopia compared with expression during myopia development in tree shrew.

Purpose: During postnatal refractive development, the sclera receives retinally generated signals that regulate its biochemical properties. Hyperopic refractive error causes the retina to produce "GO" signals that, through the direct emmetropization pathway, cause scleral remodeling that increases the axial elongation rate of the eye, reducing the hyperopia. Myopia causes the retina to generate "STOP" signals that produce scleral remodeling, slowing the axial elongation rate and reducing the myopia.

Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions.

We examined gene expression in tree shrew choroid in response to three different myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and continuous darkness (DK). Four groups of tree shrews (n=7 per group) were used. Starting 24 days after normal eye opening (days of visual experience [DVE]), the ML group wore a monocular -5D lens for 2 days.

Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery.

Gene expression in tree shrew choroid was examined during the development of minus-lens induced myopia (LIM, a GO condition), after completion of minus-lens compensation (a STAY condition), and early in recovery (REC) from induced myopia (a STOP condition). Five groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye-opening (days of visual experience [DVE]), one minus-lens group wore a monocular -5 D lens for 2 days (LIM-2), another minus-lens group achieved stable lens compensation while wearing a monocular -5 D lens for 11 days (LIM-11); a recovery group also wore a -5 D lens for 11 days and then received 2 days of recovery starting at 35 DVE (REC-2).

Gene expression signatures in tree shrew sclera in response to three myopiagenic conditions.

Purpose: We compared gene expression signatures in tree shrew sclera produced by three different visual conditions that all produce ocular elongation and myopia: minus-lens wear, form deprivation, and dark treatment.

Methods: Six groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye-opening (days of visual experience [DVE]), two minus-lens groups wore a monocular -5 diopter (D) lens for 2 days (ML-2) or 4 days (ML-4); two form-deprivation groups wore a monocular translucent diffuser for 2 days (FD-2) or 4 days (FD-4).

Light levels, refractive development, and myopia--a speculative review.

Recent epidemiological evidence in children indicates that time spent outdoors is protective against myopia. Studies in animal models (chick, macaque, tree shrew) have found that light levels (similar to being in the shade outdoors) that are mildly elevated compared to indoor levels, slow form-deprivation myopia and (in chick and tree shrew) lens-induced myopia. Normal chicks raised in low light levels (50 lux) with a circadian light on/off cycle often develop spontaneous myopia.

Response to interrupted hyperopia after restraint of axial elongation in tree shrews.

Purpose: To determine if early restraint of axial elongation in response to plus lenses increases the subsequent response to interrupted hyperopia in tree shrews.

Methods: The normal interrupted hyperopia group (n = 5) had normal visual exposure until 24 days of visual experience (VE). Then, from 24 to 45 days of VE, the animals wore binocular -4-diopter (D) lenses, which shifted the refractive state of the eyes in the direction of hyperopia.

Patterns of mRNA and protein expression during minus-lens compensation and recovery in tree shrew sclera.

Purpose: To increase our understanding of the mechanisms that remodel the sclera during the development of lens-induced myopia, when the sclera responds to putative "go" signals of retinal origin, and during recovery from lens-induced myopia, when the sclera responds to retinally-derived "stop" signals.

Methods: Seven groups of tree shrews were used to examine mRNA levels during minus lens compensation and recovery. Starting 24 days after eye opening (days of visual experience [VE]) lens compensation animals wore a monocular -5D lens for 1, 4, or 11 days.

Perspective: how might emmetropization and genetic factors produce myopia in normal eyes?

Substantial evidence has emerged over the past decades for a role of genetics in the development of human refractive error. There is also an emmetropization mechanism that uses visual signals to match the axial length to the focal plane. There has been little discussion of how these two important factors might interact.

Binocular lens treatment in tree shrews: Effect of age and comparison of plus lens wear with recovery from minus lens-induced myopia.

We examined normal emmetropization and the refractive responses to binocular plus or minus lenses in young (late infantile) and juvenile tree shrews. In addition, recovery from lens-induced myopia was compared with the response to a similar amount of myopia produced with plus lenses in age-matched juvenile animals. Normal emmetropization was examined with daily noncycloplegic autorefractor measures from 11 days after natural eye-opening (days of visual experience [VE]) when the eyes were in the infantile, rapid growth phase and their refractions were substantially hyperopic, to 35 days of VE when the eyes had entered the juvenile, slower growth phase and the refractions were near emmetropia.

The effect of age on compensation for a negative lens and recovery from lens-induced myopia in tree shrews (Tupaia glis belangeri).

We examined in tree shrews the effect of age on the development of, and recovery from, myopia induced with a negative lens. Starting at 11, 16, 24, 35 or 48days after natural eye-opening (days of visual experience [VE]), juvenile tree shrews (n=5 per group) wore a monocular -5D lens for 11days. A long-term lens-wear group (n=6) began treatment at 16days of VE and wore the lens for 30days.

Selective modulation of scleral proteoglycan mRNA levels during minus lens compensation and recovery.

Purpose: To better characterize the role of proteoglycans in scleral tissue remodeling during the development of minus lens induced myopia and during recovery in tree shrews.

Methods: Competitive reverse-transcription polymerase chain reaction (RT-PCR) was used to quantify the scleral mRNA levels for aggrecan, decorin, biglycan, and lumican in a group of tree shrews following four days of monocular -5 D lens treatment (n=5) and in a group after two days of recovery after 11 days of -5 D lens wear (n=5). Values were compared with age-matched normal animals (n=5).

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.

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.

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.

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.

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.