Changes in choroidal thickness and blood flow in response to form deprivation-induced myopia and repeated low-level red-light therapy in Guinea pigs.

PURPOSE: To evaluate ocular refractive development, choroidal thickness (ChT) and changes in choroidal blood flow in form-deprived myopia (FDM) Guinea pigs treated with repeated low-level red-light (RLRL) therapy. METHODS: Twenty-eight 3-week-old male tricolour Guinea pigs were randomised into three groups: normal controls (NC, n = 10), form-deprived (FD, n = 10) and red light treated with form-deprivation (RLFD, n = 8). Interocular refraction and axial length (AL) changes were monitored. Optical coherence tomography angiography (OCTA) measured choroidal thickness, vessel area density, vessel skeleton density and blood flow signal intensity (flux) in the choriocapillaris and medium-large vessel layers. The experimental intervention lasted 3 weeks. RESULTS: At week 3, the FD group had higher myopia and longer axial length than the NC group (all p < 0.001). The RLFD group had higher hyperopia and shorter axial length than the FD group (all p < 0.001). At week 1, the NC group had a thicker choroidal thickness than the FD group (p < 0.05). At weeks 2 and 3, the RLFD group had a thicker choroidal thickness than the FD group (p = 0.002, p < 0.001, respectively). Additionally, the NC group had higher vessel area density, vessel skeleton density and flux in the choriocapillaris layer than the FD group at the three follow-up time points (all p < 0.05). At week 3, the vessel skeleton density and flux were higher in the RLFD group than in the FD group (all p < 0.05). Correlation analysis results showed that weekly changes in refraction and choroidal thickness were negatively correlated with changes in axial length (all p < 0.05). Choroidal thickness changes were positively correlated with alterations in the vessel area density, vessel skeleton density and flux in the choriocapillaris layer, as well as vessel skeleton density and flux changes in the medium-large vessel layers (all p < 0.05). CONCLUSIONS: Repeated low-level red-light (RLRL) therapy retards FDM progression in Guinea pigs, potentially through increased choroidal blood flow in the choriocapillaris layer.

Animal models as windows into the pathogenesis of myopia: Illuminating new directions for vision health.

The incidence of myopia, particularly high myopia, is increasing annually. Myopia has gradually become one of the leading causes of global blindness and is a considerable public-health concern. However, the pathogenesis of myopia remains unclear, and exploring the mechanism underlying myopia has become an urgent scientific priority. Creating animal models of myopia is important for studying the pathogenesis of refractive errors. This approach allows researchers to study and analyze the pathogenesis of myopia from aspects such as changes in refractive development, pathological changes in eye tissue, and molecular pathways related to myopia. This review summarizes the examples of animal models, methods of inducing myopia experimentally, and molecular signaling pathways involved in developing myopia-induced animal models. This review provides solid literature for researchers in the field of myopia prevention and control. It offers guidance in selecting appropriate animal models and research methods to fit their research objectives. By providing new insights and a theoretical basis for studying mechanisms of myopia, we detail how elucidated molecular pathways can be exploited to translate into safe and effective measures for myopia prevention and control.

Form-deprivation myopia promotes sclera M2-type macrophages polarization in mice.

PURPOSE: To explore the phenotype of sclera macrophages in form-deprivation (FD) myopia mice and the effects of M2 macrophage in FD myopia development. METHODS: C57BL/6 mice were under 2 weeks of unilateral FD treatment. and they were separated into two groups, including an intraperitoneally injected(IP) vehicle group and Panobinostat (LBH589) (10 mg/kg per body weight) treatment group. All biometric parameters were measured before and after treatments, and the type and density of sclera macrophages were identified by immunofluorescence and RT-qPCR. In vitro, we analyzed the M2 macrophage and primary human sclera fibroblast (HSF) co-culture system by using the transcriptome sequencing method. Gene ontology (GO) and KEGG enrichment analyses were used to pinpoint the biological functions and pathways associated with the identified Differentially Expressed Genes (DEGs). The hub genes were investigated using the STRING database and Cytoscape software and were confirmed using RT-qPCR. RESULTS: We found that the M2-type sclera macrophage density and expression increased in FD-treated eyes. The results showed that LBH589 inhibited the M2 macrophage polarization, and reduced FDM development. GO and KEGG analyses revealed that the DEGs were predominantly involved in the synthesis and breakdown of the extracellular matrix (ECM), as well as in pathways related to ECM-receptor interaction and the PI3K-Akt signaling pathway. Five hub genes (FN-1, MMP-2, COL1A1, CD44, and IL6) were identified, and RT-qPCR validated the variation in expression levels among these genes. CONCLUSION: M2 macrophage polarization occurred in the sclera in FDM mice. Panobinostat-mediated inhibition of M2 macrophage polarization may decrease FDM progression, as M2 macrophages are crucial in controlling ECM remodeling by HSFs.

Unveiling the gut microbiota and metabolite profiles in guinea pigs with form deprivation myopia through 16S rRNA gene sequencing and untargeted metabolomics.

Aim: The aim of this study was to confirm the presence of the form deprivation myopia (FDM) guinea pig eye-gut axis and investigate the relationship between serum vasoactive intestinal peptide (VIP), lipopolysaccharides (LPS), specific gut microbiota and their metabolites. Method: 20 specific-pathogen-free (SPF) guinea pigs were divided into the FDM and the control(Con) group. Following model induction, serum levels of VIP and LPS were quantified. A combination of 16S ribosomal ribosomal Ribonucleic Acid (rRNA) gene sequencing, non-targeted metabolomics and bioinformatics analysis were employed to identify disparities in gut microbiota and metabolites between the two groups of guinea pigs. Result: Compared to the control group, FDM guinea pigs exhibited a significant trend towards myopia, along with significantly elevated concentrations of LPS and VIP (p < 0.0001). Furthermore, Ruminococcus_albus emerged as the predominant bacterial community enriched in FDM (p < 0.05), and demonstrated positive correlations with 10 metabolites, including l-Glutamic acid, Additionally, Ruminococcus_albus exhibited positive correlations with VIP and LPS levels (p < 0.05). Conclusion: The findings suggest that the Ruminococcus_Albus and glutamate metabolic pathways play a significant role in myopia development, leading to concurrent alterations in serum VIP and LPS levels in FDM guinea pigs. This underscores the potential of specific gut microbiota and their metabolites as pivotal biomarkers involved in the pathogenesis of myopia.

Brimonidine as a possible treatment for myopia.

BACKGROUND: Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of form-deprivation myopia (FDM) and the relationship between intraocular pressure (IOP) and myopia development. METHODS: Monocular form deprivation myopia (FDM) was induced in three-week-old pigmented male guinea pigs. They were treated with 3 different methods of brimonidine administration (eye drops, and subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for each method (2µg/µL, 4µg/µL, 20µg/µL, and 40µg/µL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure, refractive error and axial length (AL), respectively. RESULTS: Treatment with subconjunctival brimonidine at 40µg/µL, and intravitreal brimonidine at 2µg/µL and 4µg/µL, inhibited the development of FDM. The myopic refraction, excessive axial length, and elevation of IOP were significantly decreased. Brimonidine in eye drops was ineffective. CONCLUSION: Brimonidine at appropriate doses significantly reduced the development of FD myopia in guinea pigs. The IOP may change with FD myopia.

The role of vasoactive intestinal peptide (VIP) in atropine-related inhibition of the progression of myopia.

OBJECTIVE: This study aimed to investigate the potential involvement of vasoactive intestinal polypeptide (VIP) in myopia development and its contribution to the mechanism of action of the anti-myopia drug, atropine. METHODS: Thirty-three-week-old guinea pigs were randomly divided into normal control (NC, n = 10), monocularly form-deprived (FDM, n = 10), and FDM treated with 1% atropine (FDM + AT, n = 10) groups. The diopter and axial length were measured at 0, 2, and 4 weeks. Guinea pig eyeballs were removed at week four, fixed, and stained for morphological changes. Immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to evaluate VIP protein and mRNA levels. RESULTS: The FDM group showed an apparent myopic shift compared to the control group. The results of the H&E staining were as follows: the cells of the inner/outer nuclear layers and retinal ganglion cells were disorganized; the choroidal thickness (ChT), blood vessel lumen, and area were decreased; the sclera was thinner, with disordered fibers and increased interfibrillar space. IHC and ISH revealed that VIP's mRNA and protein expressions were significantly up-regulated in the retina of the FDM group. Atropine treatment attenuated FDM-induced myopic shift and fundus changes, considerably reducing VIP's mRNA and protein expressions. CONCLUSIONS: The findings of elevated VIP mRNA and protein levels observed in the FDM group indicate the potential involvement of VIP in the pathogenesis and progression of myopia. The ability of atropine to reduce this phenomenon suggests that this may be one of the molecular mechanisms for atropine to control myopia.

Early regional changes in retina and choroid of chicks following monocular hemifield form deprivation.

To investigate regional changes in the chick retina and choroid after hemifield form deprivation (HFD). Ten chicks were randomly and equally divided into a temporal retinal deprivation (TRD) and nasal retinal deprivation (NRD) group. HFD was induced with half-lateral translucent plastic goggles in the right eye; the left eye was kept untreated. Swept-source optical coherence tomography (SS-OCT) images obtained at 0, 3, and 72 hours (h) were analyzed using customized software. After 72 h of TRD, the retinal thickness (RT) of the treated eyes was significantly less than that of the fellow eyes in the temporal (P = 0.034) rather than the nasal (P = 0.083) region. In the NRD group, the RT of the treated eyes was thinner in both the nasal and temporal regions than that of the fellow eyes (P < 0.01). The RT alterations were more pronounced in the temporal (Δ = -16.86 ± 7.14 µm) than in the nasal (Δ = -13.44 ± 4.83 µm) region after 72-h TRD (P = 0.036), whereas the opposite was observed in the NRD group (P = 0.008). The choroidal thickness (ChT) of the treated eyes was less in both the nasal and temporal regions than that of the fellow eyes in both groups after 72-h treatment (P < 0.01). The ChT alterations were more pronounced in the temporal (Δ = -2.48 ± 8.95 µm) than in the nasal (Δ = 23.65 ± 13.58 µm) region after 72-h TRD (P = 0.021), whereas the NRD group showed the opposite effect (P = 0.019). HFD in chicks can lead to retinal and choroidal thinning in the corresponding regions.

Synchronous myopia development induced by bilateral form deprivation in chicks.

Form deprivation (FD) is a widely employed experimental paradigm, typically used to induce unilateral myopia in animal models. This model is weakened by potential influence upon the FD eye from vision in the freely-viewing contralateral eye, which could be eliminated by imposing FD in both eyes; but while a few previous studies have explored the feasibility of inducing bilateral FD in chicks, substantial discrepancies in treatment outcomes were noted. Consequently, this study aimed to establish a bilateral FD myopia model in chicks, with validation by investigating the associated ocular growth patterns, feeding, and social behavior. Six-day-old chicks were treated with bilateral (n = 21) or unilateral (n = 10) FD for 12 days; the fellow untreated eyes in the unilateral FD group served as controls. Refractive error, corneal power, and ocular axial dimensions were measured at 4-day intervals after the onset of form deprivation, with a Hartinger refractometer, a custom-made videokeratography system, and a high-resolution A-scan ultrasonographer, respectively. Body weight was monitored to assess the chick's physical development. Our results showed that birds treated with bilateral FD grew as robustly as the unilaterally form-deprived chicks, with similar or slightly heavier body weights and mortalities. Unilateral FD induced significantly higher myopia in the treated eye, with stronger corneal power, deeper anterior and vitreous chambers, and longer axial length. Moreover, either bilaterally or unilaterally FD eyes developed similar refractive error (bilateral FD, left: -28.03 ± 9.06 D, right: -28.44 ± 9.45 D; unilateral FD: -29.48 ± 8.26 D) and ocular biometric changes; but choroidal thickness was thicker in bilaterally FD eyes, rather than thinner as in unilaterally FD eyes. In addition to the highly synchronized (symmetrical, parallel) development reported previously in bilateral FD, we found in this study that the correlations between bilaterally form-deprived eyes were highest for ocular biometric parameters directly contributing to myopia development, including corneal power (r = 0.74 to 0.93), anterior chamber depth (r = 0.60 to 0.85), vitreous chamber depth (r = 0.92 to 0.94), and axial length (r = 0.90 to 0.96). The remarkably synchronized growth pattern confirmed the feasibility of the bilateral FD paradigm for future research on myopia.

Expression of early growth responsive gene-1 in the lateral geniculate body of kittens with amblyopia caused by monocular form deprivation.

OBJECTIVE: The expression of early growth responsive gene-1 (Egr-1) in the lateral geniculate body in the normal kittens and those affected with amblyopia caused by monocular visual deprivation was compared to explore the potential significance of Egr-1 in the pathogenesis of amblyopia. METHODS: A total of 30 healthy kittens were equally and randomly divided into the control (n = 15) and the deprivation group (n = 15). The kittens were raised in natural light and the right eyes of the deprived kittens were covered with a black opaque covering. Pattern visual evoked potential (PVEP) was measured before and 1, 3, and 5 weeks after covering. Five kittens from each group were randomly selected and euthanized with 2% sodium pentobarbital (100 mg/kg) during the 1st, 3rd and 5th week after covering. The expression of Egr-1 in the lateral geniculate body in the two groups was compared by performing immunohistochemistry and in situ hybridization. RESULTS: After three weeks of covering, PVEP detection indicated that the P100 wave latency in the deprivation group was significantly higher than that in the control group (P < 0.05), whereas the amplitude decreased markedly (P < 0.05). The number of the positive cells (P < 0.05) and mean optical density (P < 0.05) of Egr-1 protein expression in the lateral geniculate body of the deprivation group were found to be substantially lower in comparison to the normal group, as well as the number (P < 0.05) and mean optical density of Egr-1 mRNA-positive cells (P < 0.05). However, with increase of age, positive expression of Egr-1 in the control group showed an upward trend (P < 0.05), but this trend was not noted in the deprivation group (P > 0.05). CONCLUSIONS: Monocular form deprivation can lead to substantially decreased expressions of Egr-1 protein and mRNA in the lateral geniculate body, which in turn can affect the normal expression of neuronal functions in the lateral geniculate body, thereby promoting the occurrence and development of amblyopia.

Targeting scleral remodeling and myopia development in form deprivation myopia through inhibition of EFEMP1 expression.

The role of extracellular matrix (ECM) remodeling in the axial elongation associated with myopia has not been fully elucidated, although it is considered a significant factor. EFEMP1, a regulator of ECM, has been associated with various pathological conditions. This study aimed to examine the involvement of EFEMP1 in scleral remodeling during form deprivation myopia. The results indicate a progressive increase in EFEMP1 expression following prolonged form deprivation treatment, followed by a subsequent decrease upon recovery. To gain a deeper understanding of the mechanism of EFEMP1, we conducted transcriptome sequencing on primary scleral fibroblasts that were subjected to lentivirus-mediated overexpression of EFEMP1. Validation was performed using lentivirus-induced overexpression and shRNA targeting EFEMP1 in combination with LY294002, a PI3K inhibitor. Our findings suggest that EFEMP1 may be involved in the development of FDM by regulating the expression of the PI3K/AKT/MMP2 axis. The AAV-mediated injection of shEFEMP1 under Tenon's capsule in guinea pigs was observed to effectively delay the progression of myopia and posterior scleral remodeling. In contrast, the AAV-mediated overexpression of EFEMP1 exacerbated the development of myopia and resulted in further thinning of collagen fibers in the posterior sclera. In summary, adjusting EFEMP1 concentrations could potentially serve as a viable approach to prevent and treat myopia by influencing the remodeling process of the posterior sclera.

Defect of TIMP4 Is Associated with High Myopia and Participates in Rat Ocular Development in a Dose-Dependent Manner.

Thinning of the sclera happens in myopia eyes owing to extracellular matrix (ECM) remodeling, but the initiators of the ECM remodeling in myopia are mainly unknown. The matrix metalloproteinase (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs) regulate the homeostasis of the ECM. However, genetic studies of the MMPs and TIMPs in the occurrence of myopia are poor and limited. This study systematically investigated the association between twenty-nine genes of the TIMPs and MMPs families and early-onset high myopia (eoHM) based on whole exome sequencing data. Two TIMP4 heterozygous loss-of-function (LoF) variants, c.528C>A in six patients and c.234_235insAA in one patient, were statistically enriched in 928 eoHM probands compared to that in 5469 non-high myopia control (p = 3.7 × 10-5) and that in the general population (p = 2.78 × 10-9). Consequently, the Timp4 gene editing rat was further evaluated to explore the possible role of Timp4 on ocular and myopia development. A series of ocular morphology abnormalities in a dose-dependent manner (Timp4-/- < Timp4+/- < Timp4+/+) were observed in a rat model, including the decline in the retinal thickness, the elongation in the axial length, more vulnerable to the form deprivation model, morphology changes in sclera collagen bundles, and the decrease in collagen contents of the sclera and retina. Electroretinogram revealed that the b-wave amplitudes of Timp4 defect rats were significantly reduced, consistent with the shorter length of the bipolar axons detected by HE and IF staining. Heterozygous LoF variants in the TIMP4 are associated with early onset high myopia, and the Timp4 defect disturbs ocular development by influencing the morphology and function of the ocular tissue.

Epitranscriptomic investigation of myopia-associated RNA editing in the retina.

Myopia is one of the most common causes of vision loss globally and is significantly affected by epigenetics. Adenosine-to-inosine (A-to-I RNA) editing is an epigenetic process involved in neurological disorders, yet its role in myopia remains undetermined. We performed a transcriptome-wide analysis of A-to-I RNA editing in the retina of form-deprivation myopia mice. Our study identified 91 A-to-I RNA editing sites in 84 genes associated with myopia. Notably, at least 27 (32.1%) of these genes with myopia-associated RNA editing showed existing evidence to be associated with myopia or related ocular phenotypes in humans or animal models, such as very low-density lipoprotein receptor (Vldlr) in retinal neovascularization and hypoxia-induced factor 1 alpha (Hif1a). Moreover, functional enrichment showed that RNA editing enriched in FDM was primarily involved in response to fungicides, a potentially druggable process for myopia prevention, and epigenetic regulation. In contrast, RNA editing enriched in controls was mostly involved in post-embryonic eye morphogenesis. Our results demonstrate altered A-to-I RNA editing associated with myopia in an experimental mouse model and warrant further study on its role in myopia development.

Effect of shape deprivation on retinal thickness in myopic mice using an OCT method.

Purpose: The purpose of this study was to study in retina thickness changes in myopic mice using optical coherence tomography (OCT). Methods: There were 18 mice in the form-deprivation myopia (FDM) group，in which the left eye was not treated as a control;18 untreated mice served as a normal control group. The diopter of all mice was measured 21 days after birth (P21), before form deprivation. After 4 weeks of form deprivation (P49), the refraction, fundus, and retinal sublayer thickness of all mice were measured. Results: After 4 weeks of form deprivation, the refractive power of the right eye in the FDM group was significantly higher than that in the left eye (p < 0.05). There was no significant change in the refractive power of the left eye in the FDM group compared with the normal control group. The retina, nerve fiber layer (NFL), inner nuclear layer (INL), and outer nuclear layer (ONL) in the right eye of the FDM group were significantly thinner than those of both the FDM and control groups (p < 0.05). There was no significant change in photoreceptor (PR). Conclusion: Our study highlights that the myopic mice have decreased R thickness, which might reflect the potential pathological mechanism of myopia.

Effects of exogenous retinoic acid on ocular parameters in Guinea pigs with form deprivation myopia.

Aim: Myopia is a common chronic eye disease, this study is to investigate the effects of exogenous retinoic acid (RA) on intraocular parameters, especially choroidal thickness (CT) and retinal thickness (RT), in guinea pigs with form deprivation myopia (FDM). Methods: A total of 80 male guinea pigs were divided randomly into 4 groups: Control, FDM, FDM + RA, and FDM + Citral groups. The FDM + RA group was given 24 mg/kg RA dissolved in 0.4 mL peanut oil; the FDM + Citral group was given citral 445 mg/kg dissolved in 0.4 mL peanut oil; The other two groups were given 0.4 mL peanut oil. After 4 weeks, the refractive error (RE), axial length (AL), and intraocular pressure (IOP) of all guinea pigs were measured, and the parameters of RT and CT were obtained using enhanced depth imaging optical coherence tomography (EDI-OCT). Results: After 4 weeks, both the RE and AL in the FDM and FDM + RA groups were increased, and the RT and CT in both groups were smaller than those in the Control group (p < 0.05). Only the IOP of the right eye in the FDM + RA group increased significantly (p < 0.05). The RT of the right eye of the 4 groups was compared: Control group > FDM + Citral group > FDM group > FDM + RA group. Compared with the RT of the left eye and the right eye among the 4 groups, the RT of the right eye in the FDM and FDM + RA groups was significantly less than that in the left eye (p < 0.05). Moreover, the CT of the right eye in the Control group was greater than that in the other three groups (p < 0.0001). There was no significant difference in the CT among the FDM, FDM + RA, and FDM + Citral groups (p > 0.05). In contrast to the RT results, the CT results of the left and right eyes in the FDM + Citral group showed statistically significant differences (p < 0.05). Conclusion: RA participates in the progression of FDM as a regulatory factor. Exogenous RA can increase the RE, AL, and IOP of FDM guinea pigs, and might aggravate the retinal thinning of FDM guinea pigs. Citral can inhibit these changes, but RA might not affect the thickness of the choroid.

Changes of Melanopsin Expression in the Retina of Guinea Pig during Experimental Myopia and Recovery Period.

PURPOSE: To explore whether melanopsin is associated with the development of myopia. METHODS: Seventy-two guinea pigs (3 weeks older) were randomly assigned to 6 groups: the form-deprivation myopia (FDM) group (monocularly covering the right eye for 14 days, n = 15), the FDM recovery group (removing the eye mask for 3 days, n = 13), the lens-induced myopia (LIM) group (monocularly wearing a -4D lens for 3 days, n = 15), the LIM recovery group (removing the lens for 2 days, n = 13), and another 2 age-matched normal groups (n = 8 each). The diopter, the vitreous chamber depth (VCD), and the axial length (AXL) were measured to confirm the effect of the treatments. Immunofluorescence and western blotting methods were used to examine the expression of melanopsin in the retina. RESULTS: Immunofluorescent results showed that in the FDM group, the melanopsin intensity in the retina of experimental eyes significantly decreased compared to those of contralateral eyes, but no significant difference was observed during their recovery periods. Western blotting showed that the expression of melanopsin in the experimental eyes of the FDM group was lower than that of the contralateral eyes (fold: 1.00 versus 1.36). The expression of melanopsin in the experimental eyes increased 3 days after removing form deprivation, although a slight reduction in melanopsin expression compared to that of the contralateral eyes (fold: 1.41 versus 1.58). For the LIM group, immunofluorescent showed an obvious decreased intensity of melanopsin-labeled cells in the experimental eyes compared to the contralateral eyes. Western blotting showed that although melanopsin expression in the experimental eyes decreased compared to that of the contralateral eyes (fold: 1.00 versus 1.96), no differences were found between two eyes 2 days after lens removal (fold: 1.99 versus 2.00). CONCLUSION: The decreased expression of melanopsin in the retina may potentially participate in the development of FDM and LIM.

Identification of miR-671-5p and Its Related Pathways as General Mechanisms of Both Form-Deprivation and Lens-Induced Myopia in Mice.

Animal models have been indispensable in shaping the understanding of myopia mechanisms, with form-deprivation myopia (FDM) and lens-induced myopia (LIM) being the most utilized. Similar pathological outcomes suggest that these two models are under the control of shared mechanisms. miRNAs play an important role in pathological development. Herein, based on two miRNA datasets (GSE131831 and GSE84220), we aimed to reveal the general miRNA changes involved in myopia development. After a comparison of the differentially expressed miRNAs, miR-671-5p was identified as the common downregulated miRNA in the retina. miR-671-5p is highly conserved and related to 40.78% of the target genes of all downregulated miRNAs. Moreover, 584 target genes of miR-671-5p are related to myopia, from which we further identified 8 hub genes. Pathway analysis showed that these hub genes are enriched in visual learning and extra-nuclear estrogen signaling. Furthermore, two of the hub genes are also targeted by atropine, which strongly supports a key role of miR-671-5p in myopic development. Finally, Tead1 was identified as a possible upstream regulator of miR-671-5p in myopia development. Overall, our study identified the general regulatory role of miR-671-5p in myopia as well as its upstream and downstream mechanisms and provided novel treatment targets, which might inspire future studies.

Time-Serial Evaluation of the Development and Treatment of Myopia in Mice Eyes Using OCT and ZEMAX.

Myopia is a significant cause of visual impairment which may lead to many complications. However, the understanding of the mechanisms of myopia is still limited. In this paper, in order to investigate the development and the treatment of myopia, we analyzed the biological structure parameters of mice eyes, obtained from optical coherence tomography (OCT), and the optical performance of mice eyes calculated using ZEMAX software (ZEMAX Development Corporation, Kirkland, WA, USA) in which the optical model was built on the segment-by-segment optically corrected OCT 3D-images. Time-serial evaluation of three groups of mice eyes (form-deprivation myopia mice eyes, normal mice eyes, and atropine-treated myopia mice eyes) was performed. In addition to the biological structure parameters, imaging performance with the development of root-mean-square wavefront aberration at six filed angles was compared and analyzed. Results show that the biological structure parameters of the eye are closely related to the development of myopia. The peripheral defocus of the retina has a significant impact on inducing myopia, which verifies the new theory of myopia development. The delaying effect of atropine solution on myopia development is shown to verify the therapeutic effect of the medicine. This study provides technical support for the investigation of the myopia mechanism.

ARC/Arg3.1 expression in the lateral geniculate body of monocular form deprivation amblyopic kittens.

PURPOSE: The present study compared the expression of activity-regulated cytoskeleton-associated protein (ARC/Arg3.1) in the lateral geniculate body between form deprivation amblyopia kittens and normal kittens to examine the significance of ARC/Arg3.1 in the lateral geniculate body in the pathogenesis of amblyopia. METHODS: Twenty kittens were randomly divided into an experimental group (n = 10) and a control group (n = 10). Black opaque covering cloth was used to cover the right eye of kittens in the experimental group. Pattern visual evoked potentials (PVEP) were detected weekly in all kittens. The expression of the ARC/Arg3.1 gene was detected by immunohistochemistry and in situ hybridization, and apoptosis of lateral geniculate body cells was detected by TUNEL. RESULTS: PVEP detection showed that at the age of 5 and 7 weeks, the latency of P100 in the right eye of the experimental group was higher than that of the other three groups (P < 0.05), and the amplitude of P100 was lower than that of the other three groups (P < 0.05). The expression of ARC/Arg3.1 protein (P < 0.05) and mRNA (P < 0.05) in the lateral geniculate body of the experimental group was significantly lower than that of the control group. The level of neuronal apoptosis in the experimental group was higher than that in the control group (P < 0.05). The expression of the ARC/Arg3.1 gene was negatively correlated with the apoptosis level of lateral geniculate body neurons. CONCLUSIONS: The expression of ARC/Arg3.1 is associated with monocular form deprivation amblyopia and apoptosis of lateral geniculate body cells.

Fallopia Japonica and Prunella vulgaris inhibit myopia progression by suppressing AKT and NFκB mediated inflammatory reactions.

BACKGROUND: The increased global incidence of myopia requires the establishment of therapeutic approaches. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD). METHODS: We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJ extract (FJE) and PV extract (PVE) lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. RESULTS: FJE + PVE reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-ß1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type I collagen expression. CONCLUSIONS: Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

Myopia Development in Tree Shrew Is Associated with Chronic Inflammatory Reactions.

In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews.