A highly efficient murine model of experimental myopia

Abstract

Despite the global pandemic of myopia, the precise molecular mechanism of the onset of myopia remains largely unknown. This is partially because of the lack of efficient murine myopic models that allow genetic manipulation at low cost. Here we report a highly practical and reproducible lens-induced myopia model by specially designed frames and lenses for mice. A lens power dependent myopic induction in mice was shown until minus 30 diopter lenses. The phenotype was significantly stronger than form-deprivation myopia. We presented the protocol for precise evaluations of the state of myopia, including refraction, corneal curvature and axial length using up-to-date devices. We also found that myopic mouse eyes showed decreased visual acuity on optokinetic response examination. Finally, we confirmed the anti-myopic effect of 1% atropine using this model, which showed its potential in drug screening. The strong phenotype, stable evaluation and the potential for gene manipulation utilizing the presented method in mice will accelerate the translational research of myopia.

Visualization of the Retina in Intact Eyes of Mice and Ferrets Using a Tissue Clearing Method

“…29 Mouse models of experimental myopia showing elongation of the post-equatorial segment of the eye, as is the case in human myopia, have been developed. 30,31 Our method seems useful for investigating myopia-induced changes from the retina to the sclera at both molecular and macroscopic levels simultaneously in a whole-eye preparation. In addition to lowering eye pressure, new treatments directed at the retina and the brain could be developed.…”

Defocused Images Change Multineuronal Firing Patterns in the Mouse Retina

“…Interestingly, both monkeys [10] and chicks [12] developed myopia even after optic nerve sectioning to separate the eye from the brain. Another myopia induction method, the wearing of defocusing spectacle lenses to shift the image plane in front of or behind the retina, also induced compensating changes in eye growth to reposition the retina at the image plane in chicks [13], mouse [9,14], marmosets [15] and monkeys [16]. These studies have provided strong evidence that retina exposure to defocused images results in altered eye growth and refraction [17,18].…”

Estimation of the Minimum Effective Dose of Dietary Supplement Crocetin for Prevention of Myopia Progression in Mice

“…C57BL6/J mice (CLEA Japan, Tokyo, Japan) were raised in standard transparent mouse cages (29 × 18 × 13 cm) in an air-conditioned room maintained at 23 ± 3 • C under a 12 h dark/light cycle, with free access to a diet (MF, Oriental Yeast Co., Ltd., Tokyo, Japan) and tap water. Four or five mice were kept in one cage with 12 h on/off [13].…”

“…For the in vivo analysis, we performed the experiment of a lens-induced myopia in mice as previously reported [13]. Briefly, we designed a frame of eyeglasses for mice accommodating to the shape of the mouse head and outputted it using a three-dimensional printer.…”

“…Regarding lens-induced myopia, when equipped with minus diopter lenses, the axial length elongates to adjust the focus of the vision on the retina, which consequently makes the eye myopic. We previously revealed and reported that −30 D lenses are the most effective to produce lens-induced myopia phenotypes in mice after examining several lenses with different diopter, from −30 D to +5 D, to find which diopter is the most effective [13]. As it meant 0.003% of crocetin-containing extract was sufficient, the minimum required dose of crocetin to suppress myopia progression should be investigated for applying crocetin administration to human children and performing a randomized controlled trial.…”