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Biomedical subjects

Ruth Schippert

Publications and source records attributed to Ruth Schippert.

3 recordsLinked to original sources

Relative axial myopia in Egr-1 (ZENK) knockout mice.

PURPOSE: Experiments in chickens have implicated the transcription factor ZENK (also known as Egr-1, NGFI-A, zif268, tis8, cef5, and Krox24) in the feedback mechanisms for visual control of axial eye growth and myopia development. ZENK is upregulated in retinal glucagon amacrine cells when axial eye growth is inhibited by positive spectacle lens wear and is downregulated when it is enhanced by negative spectacle lens wear, suggesting that ZENK may be linked to an inhibitory signal for axial eye growth. This study was undertaken to determine whether a Egr-1(-/-) knockout mouse mutant, lacking ZENK completely, has longer eyes and more myopic refraction, than do Egr-1(+/)(-) heterozygous and Egr-1(+/+) wild-type mice with near-identical genetic backgrounds. METHODS: Eye growth and refractive development were tracked from day P28 to P98. Corneal radius of curvature was measured with infrared photokeratometry, refractive state with infrared photoretinoscopy, and ocular dimensions with low-coherence interferometry. As a functional vision test, grating acuity was determined in an automated optomotor task. The abundance of ZENK protein in the retina was quantified by immunohistochemistry. RESULTS: Egr-1 knockout mice had longer eyes and a relative myopic shift in refraction, with additional minor effects on anterior chamber depth and corneal radius of curvature. Paraxial schematic eye modeling suggested changes in the optics of the crystalline lens as well. With increasing age, the differences between mutant and wild-type mice declined, although the differences in refraction persisted over the observation period. Grating acuity was not affected by the lack of the Egr-1 protein during development. CONCLUSIONS: Although it has been shown that different mouse strains may have differently large eyes, the present study shows that a specific gene knockout can produce relative myopia, compared with the wild-type with near-identical genetic background. Further experiments are needed to determine whether the observed effects of Egr-1 deletion are due to changes in function within the retina or other ocular tissues or to changes of function in other systems that may affect ocular growth from outside the eye.

Animals↗

Peripheral defocus does not necessarily affect central refractive development.

PURPOSE: Recent experiments in monkeys suggest that deprivation, imposed only in the periphery of the visual field, can induce foveal myopia. This raises the hypothesis that peripheral refractive errors imposed by the spectacle lens correction could influence foveal refractive development also in humans. We have tested this hypothesis in chicks. METHODS: Chicks wore either full field spectacle lenses (+6.9 D/-7 D), or lenses with central holes of 4, 6, or 8mm diameter, for 4 days (n=6 for each group). Refractions were measured in the central visual field, and at -45 degrees (temporal) and +45 degrees (nasal), and axial lengths were measured by A-scan ultrasonography. RESULTS: As previously described, full field lenses were largely compensated within 4 days (refraction changes with positive lenses: +4.69+/-1.73 D, negative lenses: -5.98+/-1.78 D, both p<0.001, Dunnett's test, to untreated controls). With holes in the center of the lenses, the central refraction remained emmetropic and there was not even a trend of a shift in refraction (all groups: p>0.5, Dunnetts test). At +/-45 degrees , the lenses were partially compensated despite the 4/6/8mm central holes; positive lenses: +2.63 / +1.44 / +0.43 D, negative lenses: -2.57 / -1.06 / +0.06 D. CONCLUSIONS: There is extensive local compensation of imposed refractive errors in chickens. For the tested hole sizes, peripherally imposed defocus did not influence central refractive development. To alter central refractive development, the unobstructed part in the central visual field may have to be quite small (hole sizes smaller than 4mm, with the lenses at a vertex distance of 2-3mm).

Accommodation, Ocular↗

Changes in scleral MMP-2, TIMP-2 and TGFbeta-2 mRNA expression after imposed myopic and hyperopic defocus in chickens.

Induction of myopia leads to a decreased glycosaminoglycan synthesis and smaller collagen fibrillar diameters, increased levels of gelatinase-A (MMP-2) and decreased amounts of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the fibrous sclera of both chicks and tree shrews. Another factor found to be involved in altered eye growth is the transforming growth factor beta-2 (TGFbeta-2). The aim of the current study was to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA expression changes separately in the two scleral layers of chicks, following myopic and hyperopic defocus. Chicks were treated unilaterally with positive and negative lenses for different time periods. All contralateral eyes wore plano lenses and additional controls, treated binocularly with plano lenses, were included. Real-time PCR was used to measure MMP-2, TIMP-2 and TGFbeta-2 mRNA levels. Few changes in MMP-2 and TIMP-2 mRNA levels were measured following treatment with plus and minus lenses for up to 3 days. The mRNA levels of MMP-2 and TIMP-2 were either unchanged or co-regulated in both eyes, even though only the eye with the powered lens actually displayed changes in growth. In contrast, TGFbeta-2 mRNA was significantly up-regulated in the cartilaginous layer following treatment with plus lenses after 24 hr, compared to all other groups. These changes were confined to the eyes that also displayed reduced growth, suggesting a role of TGFbeta-2 in the final steps of visual eye growth regulation.

Animals↗