Biomechanical changes occur in myopic choroidal stroma and mirror those in the adjacent sclera.

Retina-derived growth signals relayed from the choroid to the sclera cause remodeling of the extracellular scleral matrix, resulting in myopic ocular elongation. However, to the best of our knowledge, no studies have assessed changes in choroidal stromal biomechanical properties during myopia progression. Here we utilized 7 µm-resolution scanning acoustic microscopy (SAM) to assess biomechanical properties (bulk modulus (K) and mass density (rho)) of choroidal stroma from guinea pig eyes with form-deprivation (FD) induced myopia.

Effect of isoflurane anaesthetic time on ocular a-scan ultrasonography measures and their relationship to age and OCT measures in the Guinea pig.

A-scan ultrasonography enables precise measurement of internal ocular structures. Historically, its use has underpinned fundamental studies of eye development and aberrant eye growth in animal models of myopia; however, the procedure typically requires anaesthesia. Since anaesthesia affects intra-ocular pressure (IOP), we investigated changes in internal ocular structures with isoflurane exposure and compared measurements with those taken in awake animals using optical coherence tomography (OCT).

Analytical methods for assessing retinal cell coupling using cut-loading.

Electrical coupling between retinal neurons contributes to the functional complexity of visual circuits. "Cut-loading" methods allow simultaneous assessment of cell-coupling between multiple retinal cell-types, but existing analysis methods impede direct comparison with gold standard direct dye injection techniques. In the current study, we both improved an existing method and developed two new approaches to address observed limitations.

SWATH Based Quantitative Proteomics Reveals Significant Lipid Metabolism in Early Myopic Guinea Pig Retina.

Most of the previous myopic animal studies employed a single-candidate approach and lower resolution proteomics approaches that were difficult to detect minor changes, and generated limited systems-wide biological information. Hence, a complete picture of molecular events in the retina involving myopic development is lacking. Here, to investigate comprehensive retinal protein alternations and underlying molecular events in the early myopic stage, we performed a data-independent Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH) based proteomic analysis coupled with different bioinformatics tools in pigmented guinea pigs after 4-day lens-induced myopia (LIM).

The Effect of Long-Term Low-Dose Atropine on Refractive Progression in Myopic Australian School Children.

Myopia will affect half the global population by 2050 and is a leading cause of vision impairment. High-dose atropine slows myopia progression but with undesirable side-effects. Low-dose atropine is an alternative.

Chick Eyes Can Recover from Lens Compensation without Visual Cues.

Significance: This study shows that nonvisual mechanism(s) can guide chick eyes to recover from myopia or hyperopia bidirectionally to regain their age-matched length. Because eye growth control is phylogenetically conserved across many species, it is possible that, in general, emmetropization mechanisms are not exclusively based on a local visual feedback system.

Purpose: Across species, growing eyes compensate for imposed defocus by modifying their growth, showing the visual controls on eye growth and emmetropization.

The effect of optic nerve section on form deprivation myopia in the guinea pig.

Myopia is induced when a growing eye wears a diffuser that deprives it of detailed spatial vision (form deprivation, FD). In chickens with optic nerve section (ONS), FD myopia still occurs, suggesting that the signals underlying myopia reside within the eye. As avian eyes differ from mammals, we asked whether local mechanisms also underlie FD myopia in a mammalian model.

Regional changes in the elastic properties of myopic Guinea pig sclera.

Biomechanical changes in the sclera likely underlie the excessive eye elongation of axial myopia. We studied the biomechanical characteristics of myopic sclera at the microscopic level using scanning acoustic microscopy (SAM) with 7-μm in-plane resolution. Guinea pigs underwent form-deprivation (FD) in one eye from 4 to 12 days of age to induce myopia, and 12-μm-thick scleral cryosections were scanned using a custom-made SAM.

Data on differentially expressed proteins in retinal emmetropization process in guinea pig using integrated SWATH-based and targeted-based proteomics.

Myopia is generally regarded as a failure of normal emmetropization process, however, its underlying molecular mechanisms are unclear. Retinal protein profile changes using integrated SWATH and MRM-HR MS were studied in guinea pigs at 3- and 21-days of age, where the axial elongation was significantly detected. Differential proteins expressions were identified, and related to pathways which are important in postnatal development in retina, proliferation, breakdown of glycogen-energy and visual phototransduction.

Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera.

Purpose: Posterior scleral remodeling accompanies myopia. In guinea pigs developing myopia, the region around the optic nerve (peripapillary zone, PPZ) rapidly expands followed by inhibition in eye size in the periphery. We studied the differential gene expression in the sclera that accompanies these changes.

Integrated SWATH-based and targeted-based proteomics provide insights into the retinal emmetropization process in guinea pig.

Unlabelled: Myopia is generally regarded as a failure of normal emmetropization process, however, its underlying molecular mechanisms are unclear. To investigate the retinal protein profile changes during emmetropization, we studied differential protein expressions of ocular growth in young guinea pigs at 3 and 21 days old respectively, when significant axial elongation was detected (P < 0.001, n = 10).

Early quantitative profiling of differential retinal protein expression in lens-induced myopia in guinea pig using fluorescence difference two-dimensional gel electrophoresis.

The current study aimed to investigate the differential protein expression in guinea pig retinas in response to lens-induced myopia (LIM) before fully compensated eye growth. Four days old guinea pigs (n=5) were subjected to ‑4D LIM for 8 days. Refractive errors were measured before and at the end of the lens wear period.

Three-dimensional OCT based guinea pig eye model: relating morphology and optics.

Custom Spectral Optical Coherence Tomography (SOCT) provided with automatic quantification and distortion correction algorithms was used to measure the 3-D morphology in guinea pig eyes (n = 8, 30 days; n = 5, 40 days). Animals were measured awake under cyclopegia. Measurements showed low intraocular variability (<4% in corneal and anterior lens radii and <8% in the posterior lens radii, <1% interocular distances).

Understanding and Treating Myopia: What More We Need to Know and Future Research Priorities.

Tantalizing treatment options to limit further global increases in the prevalence of myopia are emerging. However, to design more effective interventions, we still need to learn more about the underlying causes of myopia and the associated biological changes. Based on the outcomes of the 2015 International Myopia Conference, this short article summarizes what more we still need to discover and suggests possible priorities for future research.

The relationship between image degradation and myopia in the mammalian eye.

Background: In all species studied, myopia develops if the eye is deprived of detailed vision during development (form deprivation myopia). However, different degrees of spatial image deprivation produce different effects and have not been described in the mammalian eye. Therefore, the effect of image degradation on guinea pig emmetropisation was investigated.

Egr-1 mRNA expression is a marker for the direction of mammalian ocular growth.

Purpose: The immediate early gene Egr-1 is thought to form part of the pathway that mediates abnormal ocular growth. This study investigated whether the mRNA expression levels of Egr-1 in a mammalian retina are modulated differentially, depending on the direction of ocular growth.

Methods: To induce accelerated growth and myopia, guinea pigs wore a -5 diopter (D) lens over one eye from 4 to 11 days of age.

Salient distractors can induce saccade adaptation.

When saccadic eye movements consistently fail to land on their intended target, saccade accuracy is maintained by gradually adapting the movement size of successive saccades. The proposed error signal for saccade adaptation has been based on the distance between where the eye lands and the visual target (retinal error). We studied whether the error signal could alternatively be based on the distance between the predicted and actual locus of attention after the saccade.

Integration of defocus by dual power Fresnel lenses inhibits myopia in the mammalian eye.

Purpose: Eye growth compensates in opposite directions to single vision (SV) negative and positive lenses. We evaluated the response of the guinea pig eye to Fresnel-type lenses incorporating two different powers.

Methods: A total of 114 guinea pigs (10 groups with 9-14 in each) wore a lens over one eye and interocular differences in refractive error and ocular dimensions were measured in each of three experiments.

Temporal properties of the myopic response to defocus in the guinea pig.

Purpose: Hyperopic defocus induces myopia in all species tested and is believed to underlie the progression of human myopia. We determined the temporal properties of the effects of hyperopic defocus in a mammalian eye.

Methods: In Experiment 1, the rise and decay time of the responses elicited by hyperopic defocus were calculated in 111 guinea pigs by giving repeated episodes of monocular -4 D lens wear (from 5 to 6 days of age for 12 days) interspersed with various dark intervals.

The development of eye shape and the origin of lower field myopia in the guinea pig eye.

In a variety of species, the refractive state of the eye differs in different parts of the visual field (VF) with greater myopia in the region that views the ground ("lower field myopia"). We studied the refraction and eye shape of the normal guinea pig eye to determine what feature(s) underlie this visual adaptation. Guinea pigs (n=67) were either newborn or raised under incandescent light until 14, 37 or 45 days of age (20, 44, 20 and 11 eyes respectively).

A pharmacological approach to first aid treatment for snakebite.

Snake venom toxins first transit the lymphatic system before entering the bloodstream. Ointment containing a nitric oxide donor, which impedes the intrinsic lymphatic pump, prolonged lymph transit time in rats and humans and also increased rat survival time after injection of venom. This pharmacological approach should give snakebite victims more time to obtain medical care and antivenom treatment.

A detailed paraxial schematic eye for the White Leghorn chick.

We studied the normal ocular development of the chick (Gallus gallus domesticus, White Leghorn) up to 15 days of age using both longitudinal and cross-sectional methods. The change in refractive error, corneal curvature and axial ocular distances were used to construct schematic eyes. Equations are presented which allow prediction of refractive error changes associated with changes in vitreous chamber depth.

All-trans retinoic acid regulates the expression of the extracellular matrix protein fibulin-1 in the guinea pig sclera and human scleral fibroblasts.

Purpose: Fibulin-1 (FBLN1) mRNA is expressed in human sclera and is an important adhesion modulatory protein that can affect cell-matrix interactions and tissue remodeling. Scleral remodeling is influenced by all-trans retinoic acid (RA). Our purpose was to confirm the presence of fibulin-1 protein in guinea pig sclera and investigate the effect of RA on the expression of fibulin-1 in guinea pig sclera in vivo and in cultured human scleral fibroblasts (HSFs).

Spectacle lens compensation in the pigmented guinea pig.

When a young growing eye wears a negative or positive spectacle lens, the eye compensates for the imposed defocus by accelerating or slowing its elongation rate so that the eye becomes emmetropic with the lens in place. Such spectacle lens compensation has been shown in chicks, tree-shrews, marmosets and rhesus monkeys. We have developed a model of emmetropisation using the guinea pig in order to establish a rapid and easy mammalian model.

Emmetropization and schematic eye models in developing pigmented guinea pigs.

A model of the axial change in ocular parameters of the guinea pig eye from 2 to 825 days of age was developed and a corresponding paraxial schematic eye model applicable from 2 to 100 days of age was constructed. Axial distances increased logarithmically over time except for the lens in which growth was more complex. Over the first 30 days, ocular elongation was approximately linear: ocular length increased by 37 microm/day, the majority due lens expansion.