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An image of one mouse after the surgery. (a) An example of one mouse after the surgery for adhering the stick. (b) One mouse with eyeglasses in both sides. This figure has been modified from Jiang, X. et al 4 , available under a Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/. Please click here to view a larger version of this figure.
Source publication
Murine model of myopia can be a powerful tool for myopia research because of the comparatively easy genetic manipulation. One way to induce myopia in animals is to put clear minus lenses in front of eyes for weeks (lens-induced myopia, LIM). However, extant protocols for inducement and evaluation vary from laboratory to laboratory. Here, we describ...
Contexts in source publication
Context 1
... Some of the reagents in the dental adhesive system may be toxic. 7. Wait for about 5 min and take off the frame and the nut carefully without changing the position of the stick (Figure 3a). 8. Inject 0.75 mg/kg atipamezole hydrochloride intraperitoneally to help the mouse to recovery from the anesthesia more quickly. ...
Context 2
... the stick and put on the frames with lenses. The inducement begins at this time point (Figure 3b). NOTE: To minimize the discomfort during the recovery from anesthesia and give enough time for the dental adhesive system to coagulate, it is highly recommended to put on the frame after the mice fully recovered from anesthesia. ...
Context 3
... image of the stick adhered to the mouse head is shown in Figure 3a. The border of the cut should be at least 3 mm away from the eye to avoid influencing the function of the eyelid. ...
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Citations
... University Dusseldorf, Düsseldorf, Germany). The light cycle was maintained using a 50-lux background according to previous reports on experimental myopia induction [48,49]. ...
Myopia is becoming a leading cause of vision impairment. An effective intervention is needed. Lactoferrin (LF) is a protein that has been reported to inhibit myopia progression when taken orally. This study looked at the effects of different forms of LF, such as native LF and digested LF, on myopia in mice. Mice were given different forms of LF from 3 weeks of age, and myopia was induced with minus lenses from 4 weeks of age. Results showed that mice given digested LF or holo-LF had a less elongated axial length and thinned choroid, compared to those given native-LF. Gene expression analysis also showed that the groups given native-LF and its derivatives had lower levels of certain cytokines and growth factors associated with myopia. These results suggest that myopia can be more effectively suppressed by digested LF or holo-LF than native-LF.
... In this study, we combine a newly developed lens-induced myopia (LIM) model with genetic manipulations to investigate myopia pathways in mice (28,29). Our data confirm (10,26) that visible VL is protective but further show that delivery of VL only in the evening is sufficient for the protective effect. ...
... To investigate the effect of VL on experimental myopia, we used a newly developed LIM mouse model described elsewhere (28,29). Briefly, 0 diopter (D) lenses were attached in front of left eyes as internal controls, and −30 D lenses were attached in front of right eyes to induce myopia (Fig. 1A). ...
... LIM in Mice. LIM was induced in mice according to previous reports (28,29). Briefly, mice were put into general anesthesia by a combination of midazolam (Sandoz K.K.), medetomidine (Domitor, Orion Corporation), and butorphanol tartrate (Meiji Seika Pharma Co., Ltd.), MMB for short. ...
Significance
The increasing prevalence of myopia is a significant public health concern. Unfortunately, the mechanisms driving myopia remain elusive, limiting effective treatment options. This report identifies a refractive development pathway that requires Opn5 -expressing retinal ganglion cells (RGCs). Stimulation of Opn5 RGCs with short-wavelength violet light prevented experimental myopia in mice. Furthermore, this effect was dependent on the time of day, with evening exposure being sufficient to protect against experimental myopia. Thus, these studies suggest Opn5 RGCs may contribute to the mechanisms of emmetropization and identify the OPN5 pathway as a potential target for the treatment of myopia.
... A mouse model of UCCAO-induced ocular ischemia was developed, as previously described [14]. Briefly, under deep anesthesia with a combination of midazolam (40 µg/100 µL; Sandoz, Tokyo, Japan), medetomidine (7.5 µg/100 µL; Orion, Espoo, Finland), and butorphanol tartrate (50 µg/100 µL; Meiji Seika Pharma, Tokyo, Japan) [67], the midline of the mouse neck was incised to find the common carotid artery, and then the common carotid artery in the right side was ligated by 6−0 silk sutures. Incised wounds of the mouse were sutured and then the mouse was recovered. ...
Ocular ischemia is a common cause of blindness and plays a detrimental role in various diseases such as diabetic retinopathy, occlusion of central retinal arteries, and ocular ischemic syndrome. Abnormalities of neuronal activities in the eye occur under ocular ischemic conditions. Therefore, protecting their activities may prevent vision loss. Previously, peroxisome proliferator-activated receptor alpha (PPARα) agonists were suggested as promising drugs in ocular ischemia. However, the potential therapeutic roles of PPARα agonists in ocular ischemia are still unknown. Thus, we attempted to unravel systemic and ocular changes by treatment of fenofibrate, a well-known PPARα agonist, in a new murine model of ocular ischemia. Adult mice were orally administered fenofibrate (60 mg/kg) for 4 days once a day, followed by induction of ocular ischemia by unilateral common carotid artery occlusion (UCCAO). After UCCAO, fenofibrate was continuously supplied to mice once every 2 days during the experiment period. Electroretinography was performed to measure retinal functional changes. Furthermore, samples from the retina, liver, and blood were subjected to qPCR, Western blot, or ELISA analysis. We found that fenofibrate boosted liver function, increased serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the central nervous system, and protected against UCCAO-induced retinal dysfunction. Our current data suggest a promising fenofibrate therapy in ischemic retinopathies.
... We maintained five mice in one cage by free intake with standard chow and water. We kept them in an environment with a 12 h/12 h light/dark cycle (the dark cycle extended from 8:00 p.m. to 8:00 a.m.) at 23 ± 3 • C. We maintained the light cycle using a 50-lux background according to a previous report on experimental myopia induction [23,24]. ...
Recent studies have reported an association between myopia development and local ocular inflammation. Lactoferrin (LF) is an iron-binding protein present in saliva, tears, and mother’s milk. Furthermore, sequestering iron by LF can cause its antibacterial property. Moreover, LF has an anti-inflammatory effect. We aimed to determine the suppressive effect of LF against the development and progress of myopia using a murine lens-induced myopia (LIM) model. We divided male C57BL/6J mice (3 weeks old) into two groups. While the experimental group was orally administered LF (1600 mg/kg/day, from 3-weeks-old to 7-weeks-old), a similar volume of Ringer’s solution was administered to the control group. We subjected the 4-week-old mice to −30 diopter lenses and no lenses on the right and left eyes, respectively. We measured the refraction and the axial length at baseline and 3 weeks after using a refractometer and a spectral domain optical coherence tomography (SD-OCT) system in both eyes. Furthermore, we determined the matrix metalloproteinase-2 (MMP-2) activity, and the amount of interleukin-6 (IL-6), MMP-2, and collagen 1A1 in the choroid or sclera. The eyes with a minus lens showed a refractive error shift and an axial length elongation in the control group, thus indicating the successful induction of myopia. However, there were no significant differences in the aforementioned parameters in the LF group. While LIM increased IL-6 expression and MMP-2 activity, it decreased collagen 1A1 content. However, orally administered LF reversed these effects. Thus, oral administration of LF suppressed lens-induced myopia development by modifying the extracellular matrix remodeling through the IL-6–MMP-2 axis in mice.
... In 2006, De la Cera et al. reported the optical aberrations in mouse eyes 34 , and we have investigated the development of the refractive status and ocular growth in C57BL/6J (B6) mice since 2008 35 . To date, there have been numerous applications of mice as a myopia model [36][37][38] . ...
Spectral composition affects emmetropization in both humans and animal models. Because color vision interacts the effects of chromatic defocus, we developed a method to bypass the effects of longitudinal chromatic aberration by placing a spectral filter behind the optics of the eye, using genetic tools. Newborn C57BL/6J (B6) mice were reared in quasi-monochromatic red (410-510 nm) or blue (585-660 nm) light beginning before eye-opening. Refractive states and ocular dimensions were compared at 4, 6, 8, and 10 weeks with mice reared in normal white light. Cre recombinase-dependent Ai9 reporter mice were crossed with Chx10-Cre to obtain Chx10-Cre;Ai9 mice, expressing red fluorescent protein in retinal Cre-positive cells. Ai9 offsprings, with and without Cre, were reared under a normal visual environment. Refraction and axial components were measured as described above. Expression levels of M and S opsin were quantified by western blotting at 10 weeks. Compared with those reared in white light, B6 mice reared in red light developed relative hyperopia, principally characterized by flattening of corneal curvature. Emmetropization was not affected by blue light, possibly because the reduction in vitreous chamber depth compensated for the increase in corneal curvature. Compared with Cre-negative littermates, the refraction and axial dimensions of Chx10-Cre;Ai9 mice were not significantly different at the follow-up timepoints. M opsin levels were higher in Chx10-Cre;Ai9 mice at 10 weeks while S opsin levels were not different. Red light induced a hyperopic shift in mouse refractive development. Emmetropization was not impacted in mice with perturbed color vision caused by intrinsic red-fluorescent protein, suggesting that color vision may not be necessary in mouse emmetropization when other mechanisms are present.
Purpose:
The International Myopia Institute (IMI) Yearly Digest highlights new research considered to be of importance since the publication of the first series of IMI white papers.
Methods:
A literature search was conducted for articles on myopia between 2019 and mid-2020 to inform definitions and classifications, experimental models, genetics, interventions, clinical trials, and clinical management. Conference abstracts from key meetings in the same period were also considered.
Results:
One thousand articles on myopia have been published between 2019 and mid-2020. Key advances include the use of the definition of premyopia in studies currently under way to test interventions in myopia, new definitions in the field of pathologic myopia, the role of new pharmacologic treatments in experimental models such as intraocular pressure-lowering latanoprost, a large meta-analysis of refractive error identifying 336 new genetic loci, new clinical interventions such as the defocus incorporated multisegment spectacles and combination therapy with low-dose atropine and orthokeratology (OK), normative standards in refractive error, the ethical dilemma of a placebo control group when myopia control treatments are established, reporting the physical metric of myopia reduction versus a percentage reduction, comparison of the risk of pediatric OK wear with risk of vision impairment in myopia, the justification of preventing myopic and axial length increase versus quality of life, and future vision loss.
Conclusions:
Large amounts of research in myopia have been published since the IMI 2019 white papers were released. The yearly digest serves to highlight the latest research and advances in myopia.
