
==== Front
Adv Ophthalmol Pract Res
Adv Ophthalmol Pract Res
Advances in Ophthalmology Practice and Research
2667-3762
Elsevier

S2667-3762(24)00036-2
10.1016/j.aopr.2024.06.001
Review
Animal modeling for myopia
Zheng Lingman a
Liao Zhiyong zyliao@wzu.edu.cn
a⁎⁎
Zou Jian jianzou@zju.edu.cn
b⁎
a Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou, China
b Eye Center of the Second Affiliated Hospital, Center for Genetic Medicine, Zhejiang University International Institute of Medicine, Zhejiang University School of Medicine, Hangzhou, China
⁎ Corresponding author. jianzou@zju.edu.cn
⁎⁎ Corresponding author. zyliao@wzu.edu.cn
05 6 2024
Nov-Dec 2024
05 6 2024
4 4 173181
24 4 2024
28 5 2024
2 6 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background

Myopia is one of the most common eye diseases globally, and has become an increasingly serious health concern among adolescents. Understanding the factors contributing to the onset of myopia and the strategies to slow its progression is critical to reducing its prevalence.

Main text

Animal models are key to understanding of the etiology of human diseases. Various experimental animal models have been developed to mimic human myopia, including chickens, rhesus monkeys, marmosets, mice, tree shrews, guinea pigs and zebrafish. Studies using these animal models have provided evidences and perspectives on the regulation of eye growth and refractive development. This review summarizes the characteristics of these models, the induction methods, common indicators of myopia in animal models, and recent findings on the pathogenic mechanism of myopia.

Conclusions

Investigations using experimental animal models have provided valuable information and insights into the pathogenic mechanisms of human myopia and its treatment strategies.

Keywords

Myopia
Experimental myopia animal models
Form-deprivated myopia
Lens-induced myopia
Eye growth
Refractive development
Corneal remodeling
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pmc1 Introduction

Myopia, also known as nearsightedness, is a common refractive error, characterized by the inability of the crystalline lens to accurately focus parallel light on the retina in a relaxed state, leading to visual problems.1 Myopia tends to develop primarily and progress fastest during childhood and early adulthood, affecting a board age range.2 In the past three decades, the prevalence of myopia has continued to rise. Holden et al. estimated 1.406 billion people had myopia (22.9% of the world population) and 163 million people had high myopia (2.7% of the world population) in 2000. By 2050, the number of myopia cases is projected to rise to 4.758 billion (49.8% of the global population), and high myopia cases will increase to 938 million (9.8% of the global population).3

The vast majority of myopia is associated with excessive axial eye growth, hence the term axial myopia. In rare cases, myopia may be caused by an overly curved cornea and/or a lens with increased optical power, associated with other diseases such as keratoconus, cataracts, and intraocular inflammation.4, 5, 6 Visual regulation plays an important role in eye growth and refractive development.7 Retinal defocus and visual deprivation lead to blurred retinal imaging, which triggers compensatory axial growth and the scleral remodeling, thereby promoting the development of myopia.7, 8, 9

Myopia is a multifactorial disease. It is widely recognized that myopia results from a combination of environmental and genetic factors. Human genetic linkage studies have identified 27 loci across the genome linked to myopia (MYP1-28, Online Mendelian Inheritance in Man database).10,11 Large genome-wide association studies (GWAS) in myopia patients have identified hundreds of loci associated with refractive error.12, 13, 14, 15 Furthermore, metabolomics and proteomics studies have suggested several dozen potentially involved metabolic pathways, most of which were carried out on animal models.16,17 However, the epidemic of myopia in recent decades may be related to environmental factors, as genetic susceptibility has not substantially changed.

Myopia is not merely a refractive error; it often involves pathological changes such as elongation of the eyeball, enlargement of the eye, and thinning of the sclera.18,19 As the degree of myopia increases, high myopia is prone to serious complications, including retinal detachment, cataracts, glaucoma, posterior staphyloma, myopic maculopathy, and in severe cases, it can lead to blindness.20,21 Pathological myopia may become the second leading cause of visual impairment.19, 20, 21, 22

Since the 1970s, researchers have successively established various animal models for myopia by manipulating the visual condition during early development, either by depriving the eye of clear vision or by using defocusing lenses.23 Although there are differences between animal models and humans, analyzing the characteristics of pathological myopia developed in animal models alongside features observed in myopic patients has provided scientists with insights into the regulation of eye growth and refractive development. In this review, we summarize the characteristics of the common myopia models, the induction methods, measurable indicators of myopia in these models, and discuss the recent progress in understanding the pathogenic mechanisms of myopia.

2 Experimental models for myopia

The general structure of the eye, the role of photopic vision in emmetropization, and the visual signaling circuitry, as well as the types and patterning of retinal neurons, are highly conserved among vertebrates, making it possible to simulate human myopia in animal models. Indeed, induced myopia and the visual regulation of eye growth have been demonstrated in a wide variety of species, from primates to fish (Fig. 1). However, due to the differences in evolutionary routes and habits, there are considerable variations between species.Fig. 1 The common experimental myopic animal models and induction approaches.

Fig. 1

2.1 Chicken

The chick is the most common animal model for studying refractive development. Chick eyes exhibit highly sensitive control of refractive status, excellent optical performance, active accommodative ability, and high visual acuity. However, there are significantly differences between chick and human eyes in aspects such as scleral structure, refractive adjustment system, and photoreceptor organization.24 Chicks have a more cartilaginous sclera and possess an active accommodative system achieved through changes in both corneal and lens surface curvatures.25 Chick retinas contain rods, four single cone photoreceptors, and one double cone photoreceptor.26,27 Chick retinas do not have a fovea, but have a largely rod photoreceptor-free area centralis.28 Unlike mammals, where the lens becomes more spherical through the relaxation of the suspensory ligament, in birds, the ciliary body compresses the lens against the "annular pad" to regulate lens shape. Moreover, the avian ciliary body is composed of striated muscle, possibly mediating the rapid and brief adjustment responses observed in birds and some reptiles, while mammals have smooth muscle. The avian ciliary muscle contains nicotinic receptors instead of muscarinic receptors, making atropine ineffective for paralyzing the chick ciliary muscle.29

2.2 Monkey

Monkeys, including marmoset monkeys and rhesus macaques, have been used in myopia studies. Monkeys share the highest similarity with humans in many aspects, such as accommodative system, the ciliary muscle and its pharmacology, and photoreceptor organization.30,31 The monkey retina is rod-dominated with a cone-dominated fovea, and its ocular structure and developmental characteristics are closest to those of humans.32,33 Similar to the humans, the rhesus monkey retina possesses three types of cones with short-, middle- and long-wavelength sensitivities. The marmoset retina exhibits a polymorphism of visual pigments, either dichromatic or trichromatic. The high similarity between monkeys and humans allows the monkey model to better study the mechanisms of myopia, the visual regulation of eye growth, and reactions to medicine. Zeng et al. suggested that elderly monkeys could serve as a model for pathological features similar to age-related macular degeneration and high myopia in humans.34 However, the limitations of the monkey model, including long experimental cycles, high costs, poor compliance, and difficulties in conducting experiments with large scale sample, restrict its application.

2.3 Mouse

The mouse is a well-established animal model for human diseases. Similar to other vertebrate species, mice developed experimental myopia in response to both visual form deprivation and imposed optical defocus,35 and photopic visual input is necessary for mouse emmetropization.36 Both the guinea pig and mouse are rodents. Like the guinea pig, the mouse retina is dichromatic and lacks a fovea.37 Unlike diurnal guinea pigs, mice are classified as nocturnal animals, although they are also active during the day.38 97% of photoreceptors in the mouse retina are rods.39 Mice have poor optical performance, lack of accommodative ability, and do not have a fovea in the retina.40 Compared to chickens and guinea pigs, changes in refractive power and eye growth due to visual experience in mice are slow.41,42 Additionally, mice have relatively poor spatial vision, at least 60 times worse than humans.43 Mouse eyes are small (approximately 3.3 ​mm in axial length), making accurate measurements of axial length and refractive power challenging without high resolution.41,44

2.4 Rabbit

Rabbits also serve as a common animal model for myopia through the application of form-deprivation or defocusing lenses.45 The rabbit retina is dichromatic and lacks of fovea.46 The size and anatomy of rabbit eyeballs are similar to those of humans. Ophthalmic surgery and examination methods used for humans can be directly applied to rabbits. The cost is affordable and these features facilitate the frequent use of rabbits in the preclinical assessment of ophthalmic drugs and surgical strategies.47,48

2.5 Fish

Teleost fish offer a unique vertebrate model for studying eye diseases and development. Unlike mammals, fish eyes and retinas can continuously grow throughout life. The fish cornea is essentially nonrefractive due to the aquatic environment. The refractive power of the fish eye is provided by moving the lens along the pupillary plane or pupillary axis,49 rather than by deforming the lens in birds and mammals. Furthermore, fish exhibits significant differences from human in photoreceptors. Zebrafish have tetrachromatic vision. The four types of cones are organized into precise two-dimensional arrays called cone mosaics across almost the entire retina,50,51 which is associated with the fish visual acuity and distance perception.52,53 Despite these differences from humans, fish offer numerous advantages as a vertebrate model with eyes similar to human in structure and function. These advantages include rapid growth and regeneration, transparent eye structures, the feasibility of large-scale screening, the availability of genetic and gene-editing tools, and low cost. These features make fish models widely used in ophthalmic research.

Refractive errors can be induced in tilapia fish through both form-deprivation and imposed defocus, and these errors can be reversed when the inducing conditions are discontinued.54 Currently, there is limited literature on induced myopia models in zebrafish. However, a series of zebrafish genetic models demonstrate myopia-like features. Knockout of genes in zebrafish, such as lrpap1, lrp2, bugeye, and lumican, leads to increased eye axial length and disorders in the sclera.55, 56, 57 Disruption of cone mosaics caused by crb2b gene knockout induces myopia phenotypes in zebrafish.52 A zebrafish model with excessive expansion of sclera, generated by morpholino injection targeting lumican, has been successfully used for drug screening.58 GWAS studies have identified hundreds of genes potentially associated with myopia. The ease of genetic manipulation in zebrafish makes it possible to analyze the function of these genes in myopia using this model. Quint et al. have tested nine genes identified by GWAS and showed that three of them (LAMA2, LRRC4C, and KCNQ5) play roles in refractive development.59

2.6 Other species

Myopia has been induced in other species, such as tree shrew,60,61 guinea pig,62,63 grey squirrel,64 and cat,65 dog,66, 67, 68 and sheep.69

Tree shrews can develop myopia under conditions of visual deprivation.61 Tree shrews are dichromatic, possessing cones sensitive to short and long wavelengths.70 The tree shrew retina does not have a central fovea. The central region of the retina mainly consists of cones, with rods accounting for about 1%–14% of the total photoreceptors.71 Furthermore, the breeding limitation of tree shrews also restricts their use as a model organism.

Guinea pigs develop fast from deprivation myopia and corneal curvature regulation, and their ocular growth and refractive error are visually regulated in response to imposed myopic and hyperopic defocus.63 Guinea pigs have the advantage of high reproductive capacity and cost-effective. Compared to other animal models like chickens and mice, guinea pigs have a larger body size, making them easier to handle surgically. However, the guinea pig model has its limitations. Guinea pigs are dichromatic and do not have a fovea.72 They may not exhibit an active accommodative response, and their vision is relatively weak.73

The domestic dog is a dichromatic vision animal,66 and has been proven to be an important large animal model for many human genetic retinal diseases.67 It has been reported that spontaneous myopia is very common in certain breeds of dogs. However, the cause of the myopia appears to be refractive, stemming from a steeper, more powerful crystalline lens and an elongated vitreous chamber depth, rather than from excess axial elongation. The axial length and corneal curvature of myopic eyes did not differ significantly from non-myopic eyes.68

A recent study reported a spontaneous myopia and loss of cone function in a sheep model of achromatopsia caused by CNGA3 mutation. The day-blind sheep had a significantly longer vitreous axial length compared to WT.69

3 Induction of myopia in animal models

Since 1970s, researchers have developed several methods to induce myopia in animal models. The classic methods are form-deprivation myopia (FDM) and lens-induced myopia (LIM).

3.1 Form-deprivation myopia (FDM)

Form-deprivation myopia develops when light is blocked from reaching the retina through the use of eyelid sutures, diffusion eyepieces, headgear, or lenses, thus preventing the formation of a clear image. The FDM model was first established by Wiesel et al., in 1977 by suturing the eyelids of young monkeys23 and has since been widely applied in various animal models, such as chick,74 monkey,75 mouse,35 rabbit,45 tree shrew,61 guinea pig63 and tilapia fish.76 Eyelid suturing may lead to eyelid adhesion, corneal compression, infections, and other adverse reactions, affecting experimental outcomes and making it challenging to create a model of myopia recovery. In contrast, diffuser goggles do not compress the cornea, are easy to use, and are widely applied in FDM models.

3.2 Lens-induced myopia (LIM)

Lens-induced myopia develops by placing negative lenses on animals, causing images to form behind the retina and inducing compensatory elongation of the eye axis. In 1983, Williams et al. successfully established the LIM model by fitting negative lenses on marmosets.77 More recently, methods such as laser surgery,78 wearing concave lenses,79 and others have been used to defocus the retina, leading to the development of LIM.

In recent years, multiple studies suggest that peripheral hyperopic defocus can stimulate eye growth and is one of the risk factors for the onset and progression of myopia.80 Lenses with special peripheral optical designs or bifocal lenses are used in animal models to investigate the roles of peripheral defocus in myopia. These studies indicate that peripheral hyperopic defocus induces a decrease in central refractive power and an increase in eye axial length, whereas peripheral myopic defocus slows myopia progression.81, 82, 83

3.3 Light induction

Myopia models can also be induced by rearing animals in dim light conditions. Epidemiological studies and experiments in animal models support the association between light intensity and myopia.84 Chicks reared under continuous dim light developed the eye enlargement and suppressed corneal growth.85 In primates, She et al.75 suggested that dim light was not a strong myopia stimulus by itself, but it can impair the optical regulation of refractive development. In mice, Landis et al.86 showed that animals exposed to either scotopic or photopic lighting developed significantly less severe myopic refractive shifts than mice exposed to mesopic lighting.

Several animal studies show that monochromatic light of different wavelengths regulates eye growth and development. She et al.61 reported that long-wavelength monochromatic light inhibited myopia development in tree shrews. Strickland et al.87 discovered that short-wavelength ultraviolet light could slow down the development of mouse eye refraction, producing hyperopic responses, and also inhibit lens-induced myopia. Tian et al.88 reported that green light at lower temporal frequency led to myopia and longer axial length, while blue light at a higher temporal frequency resulted in hyperopia and shorter axial length in guinea pigs. Quint et al.89 reported exposure to cyan or red light inhibited the axial growth of zebrafish.

3.4 Behavior induction

Near-work is considered as an important factor for myopia development.90 Fu et al.62 established a near-work behavior animal model for myopia using guinea pigs. Animals were placed in cylindrical cages with vertical square wave gratings, providing an average viewing distance for short, medium, and long distances, while maintaining the same light intensity for 14 days of treatment. The results showed that guinea pigs in the near-work group exhibited a shift towards myopia. However, there are currently few established behavioral animal models for myopia.

3.5 Genetic models

Given the importance of genetic factors in myopia, the genetic models are irreplaceable for the functional analysis of candidate genes for myopia. Genetic linkage studies have identified a series of myopia associated genes.91, 92, 93, 94, 95, 96, 97, 98 Genetic evidence in animals has confirmed the roles of certain genes in myopia, including lumican (MYP3),99 VIPR2 (MYP17),100 ZNF644 (MYP21),101 and LRPAP1 (MYP23).57 Mutations in genes associated with complete congenital stationary night blindness (cCSNB), such as GPR179, NYX, LRIT33, TRPM1 and GRM6, present with high myopia. Loss of these genes in mice promotes susceptibility to myopia induction.102 Mutations in genes causing disorders in photoreceptors, such as OPN1LW (MYP1),103 ARR3 (MYP26),104 GNAT1105 and GNAT2,106 and GLRA2,107 can also be associated with high myopia in humans and mice by impairing photoperception and visual transmission. Depletion of matrix metalloproteinases (MMPs), which mediate scleral extracellular matrix (ECM) degradation and scleral thinning, relieved FDM-induced myopia in mice, and vice versa.108 Knockout of TGF-β regulators such as A2AR109 and LRPAP1110 promotes development of myopia with increased axial length and altered scleral collagen fiber structure in mice. More genes have been identified as myopia-associated genes by GWAS. Knockout of a portion of these genes presents a myopic phenotype and can serve as genetic models for myopia. For example, depletion of myopia-associated genes LAMA2, LRRC4C, and KCNQ5 identified by GWAS affected the refractive development in zebrafish.59

4 Common measurable indicators for myopia

Refraction is determined by the coordinated contributions of ocular biometric components such as axial length, anterior chamber depth, vitreous chamber depth, corneal curvature, and lens shape and thickness. Thus, these ocular biometric components are used as the indicators for myopia in animal models.

Typically, the axial distance from the cornea to the retina is referred to as the axial length of the eye. The distance from the posterior corneal surface to the anterior lens surface is referred to as anterior chamber depth. The distance from the posterior lens surface to the vitreous-retina interface is referred as vitreous chamber depth. Optical coherence tomography, as well as A- or B- scan ultrasonography technologies, is frequently employed for imaging the eyeball and measuring ocular biometry in experimental myopic animals.17,52,89,111, 112, 113 Autorefractor keratometry is usually used to measure the corneal curvature in myopic animals. Blood flow within the choroid can be assessed using laser doppler velocimetry and flowmetry, laser interferometry, and laser speckle flowgraphy.114 The ultrastructure of the corneal extracellular matrix can be visualized using a transmission electron microscope. In zebrafish, methods to measure visual acuity and visual distance have been established.52,115 Furthermore, a series of studies has identified dopamine in the retina as an important neurotransmitter regulating the ocular refractive development in humans and animals.116, 117, 118, 119 Levels of dopamine and its primary metabolite, 3,4-dihydroxyphenylacetic acid, are used as a molecular indicators in myopic animals.

5 Cellular and molecular biology of myopia

Although myopia can be triggered by an overly curved cornea and other factors,4,5,120 which have been also observed in some animal models of myopia,7 axial myopia is primarily caused by excessive axial growth of the eyeball under visual accommodation. The signaling for eye growth and refractive development in visual accommodation appears to be located within the eye. Surgical or pharmacologic blockade of vision, such as transection of the optic nerve, bilateral surgical removal of the striate cortices, and sensory deafferentation by sectioning the trigeminal nerve, did not prevent induced myopia or its recovery when the induction was terminated in multiple animals.7 It is currently believed that the shape and size of the eyeball are primarily determined by the sclera,18 with a possible contribution from the choroid.121

The sclera is a layer of dense connective tissue that forms the outermost layer of the eyeball. Human scleral tissue is composed of collagen fibrils embedded in a matrix of elastin, proteoglycans and non-collagenous glycoproteins.18 The sclera is a dynamic tissue. The components, thickness, and ultrastructure of the scleral ECM undergo remodeling to adapt to the state of the eye. ECM remodeling leads to changes in scleral biomechanical properties, which in turn define the eye size and refraction. ECM loss and scleral thinning (especially at the posterior pole) are observed in both in highly myopic human eyes and experimental myopic animal eyes.18,122, 123, 124 ECM loss and scleral thinning result in an increase of viscoelasticity and an decreased tensile strength of the sclera, allowing for the elongation of the eye axis.

Scleral remodeling is a dynamic process involving the continuous synthesis and degradation of the ECM. Any alterations in the scleral ECM components or the regulation of scleral ECM synthesis and degradation may lead to changes in scleral shape, which in turn could dramatically affect vision. Indeed, mutations in collagen genes, including COL1A1,125 COL2A1,126 COL18A1127 have been identified as high risk factors for myopia. Transforming growth factor β (TGF-β), MMPs and tissue inhibitors of metalloproteinases (TIMPs) play a central role in scleral remodeling. TGF-β is a multipotent growth factor that plays a critical role in embryo development and tissue homeostasis by regulating cell growth, inflammation, apoptosis, and extracellular matrix synthesis.128 TGF-β is essential in regulating the production of the scleral extracellular matrix.129,130 TGF-β is also known to modulate the expression of MMPs, which can cleave collagens and degrade ECM, resulting in scleral remodeling.131 Clinical and animal studies have shown increased expression of TGF-β2, MMPs and TIMPs in myopic eye tissues.108,132,133

More signaling pathways have been identified as the critical regulators of myopia (Fig. 2).134 Dopamine is widely known as a key neurotransmitter regulating ocular refractive development in humans and animals.116 Other transmitters and signaling molecules are involved in eye growth and refractive development include GABAb,135 nitric oxide,136 and adenosine.137 Cytokines, including fibroblast growth factor (FGF),138 insulin like growth factor (IGF),139 bone morphogenetic protein (BMPs),140 vascular endothelial growth factor (VEGF),141 retinoic acid (RA),142 and WNT143 are also known to participate in the process. Cellular responses, such as scleral hypoxia,144,145 oxidative stress,146 and endoplasmic reticulum stress147, 148, 149 are also involved in the regulation of scleral remodeling and myopia development. Lin et al. have reported that augmentation of scleral glycolysis promotes myopia via the scleral glycolysis-lactate-histone lactylation pathway.150 Pan et al. has reported that dietary ω-3 polyunsaturated fatty acids play a protective role against myopia.151 Moreover, miRNAs, circRNAs and epigenetic regulation have been shown to regulate scleral remodeling.150,152, 153, 154, 155, 156, 157 These signaling molecules are primarily derived from retina, RPE, choroid and sclera.Fig. 2 The regulators of scleral ECM remodeling and myopia development. TGF-β and MMPs/TIMPs are the key regulators of scleral ECM remodeling. Arrows represents causal relationships supported with published evidences. Dasharrwos represents possible causal relationships without evidence yet.

Fig. 2

The choroid is a highly vascularized connective tissue located between the RPE and the sclera.158 It is a dynamic structure, and its thickness is modulated in response to various cues, including physiological and pharmacological influences, circadian rhythm and optical defocus.112,159,160 Choroidal thickness has been shown to predict myopia development. Thinner choroids are always associated with higher degree the myopia.8 Anti-myopia treatments have induced significant increases in choroidal thickness in several clinical studies.161,162 The choroid provides nutrients and oxygen to the sclera and retina, influences their metabolism. Increased choroidal blood perfusion induced by the vasodilator prazosin treatment inhibited FDM myopia in guinea pigs, and vice versa.163,164 Choroidal thickness and choroidal blood perfusion were significantly decreased in both spontaneous and induced myopic guinea pigs.165 Pharmacological anti-myopia treatments or intense light significantly inhibited myopia development and the decrease in choroidal blood perfusion in FDM-induced myopic eyes in guinea pigs.163 Moreover, the choroid can secrete a variety of factors involved in scleral remodeling during myopia development, including TGF-β, VEGF, hepatocyte growth factor (HGF), RA, FGF, nitric oxide, dopamine, MMPs and TMIPs, and acetylcholine.

The first signals that visually regulate eye growth may originate from the retina since the retina is the only organ that senses light. Evidences have shown that the retina plays an important role in the development of myopia through various mechanisms. It is widely accepted that light conditions, such as light intensity, light wavelength, and intermittent/continuous light exposure, affect on eye axis growth and myopia development.166, 167, 168 Outdoor exposure and repeated low-level red-light treatment are effective therapeutic approaches for the retardation of myopia.168, 169, 170 Impaired photoperception and visual transmission are risk factors of high myopia. Photoreceptor disorders caused by dysfunction of genes, including OPN1LW (MYP1),103 ARR3 (MYP26),104 PRGR,171 GNAT1105 and GNAT2,106 GLRA2,107 PDE4B,172 PDE6B,173 and EGR1,174 are also associated with high myopia in humans and mice. Mutations in cCSNB associated genes, such as GPR179,175 NYX,176 LRIT3,175 TRPM1175 and GRM6,177 presents ON-biplaor cells dysfunction with high myopia. Loss of these genes in mice promotes susceptibility to myopic induction.102 Disruption of amacrine cells using colchicine suppresses axial growth of the eye in chicks.178 Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin have been identified as novel photosensitive cells in the retina.179,180 Ablation of ipRGC or melanopsin attenuated FDM induced myopia in mice, and vice versa.181,182 Additionally, it has been reported that Müller cells and astrocytes, which can secrete a variety of factors, are activated in myopic eyes.183 Omics studies in human and animal myopic eyes have shown that the expression patterns of hundreds of genes are significantly altered, with both up-regulated and down-regulated expression.16 However, the causal relationships between gene expression alterations and myopia development need further investigated.

6 Conclusions

In summary, visual regulation plays an important role in eye growth and refractive development, and myopia can be effectively induced by FDM and LIM in all these animal models. These animal models offer researchers a controlled experimental platform to gain deeper insight into the development of myopia. Studies in experimental myopic animals have provided valuable insights into the mechanisms, risk factors, and treatment for myopia. However, each animal model has its own advantages and disadvantages due to species differences. For example, chicks and rabbits exhibit excellent optical performance and are frequently used in the preclinical assessment of ophthalmic drugs and surgical strategies. Monkeys can serve as the best model for pathological features similar to humans. Mouse model is widely used to explore the cellular and molecular mechanism of myopia. Zebrafish model is suitable for the large screening of candidate genes and drugs. It is worth to note that the findings from animal models may sometimes differ significantly from those observed in human myopia.

Study approval

Not applicable for a review article.

Funding

This research was sponsored by the 10.13039/501100001809 National Natural Science Foundation of China (10.13039/501100001809 NSFC ) Projects 82371870 to JZ.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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