Form Deprivation Research Articles

Expression of early growth responsive gene-1 in the visual cortex of monocular form deprivation amblyopic kittens

PurposeThe present study compared the expression of early growth responsive gene-1 (Egr-1) in visual cortex between amblyopia kittens and normal kittens, and to explore the role of Egr-1 in the pathogenesis of amblyopia.MethodsA total of 20 healthy kittens were randomly divided into deprivation group and control group with 10 kittens in each group. Raised in natural light, and covered the right eye of the deprived kittens with a black opaque covering cloth. Pattern visual evoked potentials (PVEP) were measured before and at the 1st, 3rd and 5th week after covering in all kittens. After the last PVEP test, all kittens were killed. The expression of Egr-1 in the visual cortex of the two groups was compared by immunohistochemistry and in situ hybridization.ResultsPVEP detection showed that at the age of 6 and 8 weeks, the P100 wave latency in the right eye of deprivation group was higher than that in the left eye of deprivation group (P < 0.05) and the right eye of control group (P < 0.05), while the amplitude decreased (P < 0.05). The number of positive cells (P < 0.05) and mean optical density (P < 0.05) of Egr-1 protein expression in visual cortex of 8-week-old deprivation group were lower than those of normal group, as well as the number (P < 0.05) and mean optical density of Egr-1 mRNA-positive cells (P < 0.05).ConclusionsMonocular form deprivation amblyopia can lead to the decrease of Egr-1 protein and mRNA expression in visual cortex, and then promote the occurrence and development of amblyopia.

Dietary ω-3 polyunsaturated fatty acids are protective for myopia

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

Visually guided chick ocular length and structural thickness variations assessed by swept-source optical coherence tomography.

Chicks are an excellent model for studying myopia. To study the change of the ocular structures in chicks, ultrasound is mostly used. However, it suffers from limited spatial resolution. In this study, we investigated the axial length (AL) and the thickness of different ocular structures in chicks' eye undergoing visually induced changes using a swept-source optical coherence tomography (SS-OCT) system in vivo. Two groups of chicks wore a translucent plastic goggle (n = 6) over the right eye to induce form-deprivation myopia. Following 12 days of form deprivation, goggles were removed in one group of chicks (n = 3), and they were allowed to experience 5 days of unrestricted vision (recovery). Goggles remained in place for a total of 17 days for the remaining 3 chicks. A separate group of 3 chicks were untreated and served as normal control. Ocular dimensions were measured in control, myopic, and recovered eyes using an SS-OCT system. We found myopic chick eyes had significantly thicker AL, lens thickness (LT), anterior chamber depth (ACD), and vitreous chamber depth (VCD), but significantly thinner retina thickness (RT) and choroid thickness (ChT) compared to the control eyes. Following 5 days of recovery, the cornea thickness (CT), retina pigment epithelium thickness (RPET), and ChT were significantly thicker, while the ACD and LT became significantly thinner compared to that of myopic eyes. SS-OCT can serve as a promising tool to provide measurements of the entire ocular structures, for evaluating the change of thickness and depth of different ocular structures in chicks in vivo. The change of AL in the myopic and recovered chick eyes can be attributed to the thickness alterations of different ocular structures. Altogether, this work demonstrated the feasibility of SS-OCT in chick myopic research and exhibited new insights into the changes of ocular structures in chicks experiencing myopia after unrestricted vision recovery.

Declines in PDE4B activity promote myopia progression through downregulation of scleral collagen expression

Myopia is the most common cause of a visual refractive error worldwide. Cyclic adenosine monophosphate (cAMP)-linked signaling pathways contribute to the regulation of myopia development, and increases in cAMP accumulation promote myopia progression. To pinpoint the underlying mechanisms by which cAMP modulates myopia progression, we performed scleral transcriptome sequencing analysis in form-deprived mice, a well-established model of myopia development. Form deprivation significantly inhibited the expression levels of genes in the cAMP catabolic pathway. Quantitative real-time polymerase chain reaction analysis validated that the gene expression level of phosphodiesterase 4B (PDE4B), a cAMP hydrolase, was downregulated in form-deprived mouse eyes. Under visually unobstructed conditions, loss of PDE4B function in Pde4b-knockout mice increased the myopic shift in refraction, −3.661 ± 1.071 diopters, more than that in the Pde4b-wildtype littermates (P < 0.05). This suggests that downregulation and inhibition of PDE4B gives rise to myopia. In guinea pigs, subconjunctival injection of rolipram, a selective inhibitor of PDE4, led to myopia in normal eyes, and it also enhanced form-deprivation myopia (FDM). Subconjunctival injection of dibutyryl-cyclic adenosine monophosphate, a cAMP analog, induced only a myopic shift in the normal visually unobstructed eyes, but it did not enhance FDM. As myopia developed, axial elongation occurred during scleral remodeling that was correlated with changes in collagen fibril thickness and distribution. The median collagen fibril diameter in the FDM + rolipram group, 55.09 ± 1.83 nm, was thinner than in the FDM + vehicle group, 59.33 ± 2.06 nm (P = 0.011). Thus, inhibition of PDE4 activity with rolipram thinned the collagen fibril diameter relative to the vehicle treatment in form-deprived eyes. Rolipram also inhibited increases in collagen synthesis induced by TGF-β2 in cultured human scleral fibroblasts. The current results further support a role for PDE enzymes such as PDE4B in the regulation of normal refractive development and myopia because either loss or inhibition of PDE4B function increased myopia and FDM development through declines in the scleral collagen fibril diameter.

Dopamine Imaging in Living Cells and Retina by Surface-Enhanced Raman Scattering Based on Functionalized Gold Nanoparticles.

Retinal dopamine is believed to be involved in the development of myopia, which is projected to affect almost half of the world population's visual health by 2050. Direct visualization of dopamine in the retina with high spatial precision is essential for understanding the biochemical mechanism during the development of myopia. However, there are very few approaches for the direct detection of dopamine in the visual system, particularly in the retina. Here, we report surface-enhanced Raman scattering (SERS)-based dopamine imaging in cells and retinal tissues with high spatial precision. The surface of gold nanoparticles is modified with N-butylboronic acid-2-mercaptoethylamine and 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester), which shows excellent specific reaction with dopamine. The existence of dopamine triggers the aggregation of gold nanoparticles that subsequently form plasmonic hot spots to dramatically increase the Raman signal of dopamine. The as-synthesized SERS nanoprobes have been evaluated and applied for dopamine imaging in living cells and retinal tissues in form-deprivation (FD) myopia guinea pigs, followed by further investigation on localized dopamine levels in the FD-treated mice. The results suggest a declined dopamine level in mice retina after 2-week FD treatment, which is associated with the development of myopia. Our approach will greatly contribute to better understanding the localized dopamine level associated with myopia and its possible treatments. Furthermore, the imaging platform can be utilized to sensing other important small molecules within the biological samples.

The Role of Retinal Connexins Cx36 and Horizontal Cell Coupling in Emmetropization in Guinea Pigs.

PurposeThe purpose of this study was to determine whether retinal gap junctions (GJs) via connexin 36 (Cx36, mediating coupling of many retinal cell types) and horizontal cell (HC-HC) coupling, are involved in emmetropization.MethodsGuinea pigs (3 weeks old) were monocularly form deprived (FD) or raised without FD (in normal visual [NV] environment) for 2 days or 4 weeks; alternatively, they wore a −4 D lens (hyperopic defocus [HD]) or 0 D lens for 2 days or 1 week. FD and NV eyes received daily subconjunctival injections of a nonspecific GJ-uncoupling agent, 18-β-Glycyrrhetinic Acid (18-β-GA). The amounts of total Cx36 and of phosphorylated Cx36 (P-Cx36; activated state that increases cell-cell coupling), in the inner and outer plexiform layers (IPLs and OPLs), were evaluated by quantitative immunofluorescence (IF), and HC-HC coupling was evaluated by cut-loading with neurobiotin.ResultsFD per se (excluding effect of light-attenuation) increased HC-HC coupling in OPL, whereas HD did not affect it. HD for 2 days or 1 week had no significant effect on retinal content of Cx36 or P-Cx36. FD for 4 weeks decreased the total amounts of Cx36 and P-Cx36, and the P-Cx36/Cx36 ratio, in the IPL. Subconjunctival 18-β-GA induced myopia in NV eyes and increased the myopic shifts in FD eyes, while reducing the amounts of Cx36 and P-Cx36 in both the IPL and OPL.ConclusionsThese results suggest that cell-cell coupling via GJs containing Cx36 (particularly those in the IPL) plays a role in emmetropization and form deprivation myopia (FDM) in mammals. Although both FD and 18-β-GA induced myopia, they had opposite effects on HC-HC coupling. These findings suggest that HC-HC coupling in the OPL might not play a significant role in emmetropization and myopia development.

Gene expression profiles of myopic mouse scleral fibroblasts: a bioinformatics analysis based on single-cell RNA sequencing

To investigate the changes in gene expression profiles of mouse scleral fibroblasts after myopia using single-cell RNA sequencing technology and explore the mechanism of dysfunction of the scleral fibroblasts in myopia. Normal healthy C57BL/6J mice were randomly divided into negative control group and myopia model group (n=6), and in the latter group, form deprivation myopia was induced in the right eye using translucent goggles. Single cell capture was performed in the right eye to obtain the scleral fibroblasts for RNA sequencing. The differentially expressed genes (DEGs) were screened and GO and KEGG analyses were carried out for functionally significant enrichment analysis. Comparison of the gene expression profiles identified a total of 169 DEGs between the myopia model group and the negative control group (P>0.05), including 112 up-regulated and 57 down-regulated genes. GO function analysis showed that the DEGs were involved in leukocyte aggregation, differentiation and adhesion and other inflammation-related terms; ATP metabolism and binding, redox process, oxidative stress response, oxidative phosphorylation and other GO terms related to hypoxia; protein folding, protein transport, negative regulation of protein metabolism, endoplasmic reticulum (ER), ER cavity, ER stress and other biological processes related to protein and ER stress. KEGG analysis analysis showed that the significantly enriched pathways of the DEGs involved mainly the TCA cycle, oxidative phosphorylation, PPAR signaling, oxidative phosphorylation and other pathways related to hypoxia; MAPK signaling pathway related to inflammation; leukocyte transendothelial transport; and protein-related Parkinson's disease, Huntington's disease, protein digestion and absorption pathways. The dysfunction of the scleral fibroblasts occurs in myopia through complex mechanisms involving inflammation, hypoxia, protein regulation, and ER stress-related gene expression and pathway regulation.

Anti-Inflammatory Effects of Resveratrol on Human Retinal Pigment Cells and a Myopia Animal Model.

Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on myopia. To this end, we examined its anti-inflammatory influence on human retinal pigment epithelium cells and in a monocular form deprivation (MFD)-induced animal model of myopia. In MFD-induced myopia, resveratrol increased collagen I level and reduced the expression levels of matrix metalloproteinase (MMP)2, transforming growth factor (TGF)-β, and nuclear factor (NF)-κB expression levels. It also suppressed the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Resveratrol exhibited no significant cytotoxicity in ARPE-19 cells. Downregulation of inflammatory cytokine production, and inhibition of AKT, c-Raf, Stat3, and NFκB phosphorylation were observed in ARPE-19 cells that were treated with resveratrol. In conclusion, the findings suggest that resveratrol inhibits inflammatory effects by blocking the relevant signaling pathways, to ameliorate myopia development. This may make it a natural candidate for drug development for myopia.

Intravitreal brimonidine inhibits form-deprivation myopia in guinea pigs

BackgroundThe use of ocular hypotensive drugs has been reported to attenuate myopia progression. This study explores whether brimonidine can slow myopia progression in the guinea pig form-deprivation (FD) model.MethodsThree-week-old pigmented male guinea pigs (Cavia porcellus) underwent monocular FD and were treated with 3 different methods of brimonidine administration (eye drops, subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for intravitreal injection (2 μg/μL, 4 μg/μL, 20 μg/μL, 40 μg/μL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure (IOP), refractive error and axial length (AL), respectively. On day 21, guinea pigs were sacrificed for RNA sequencing (RNA-seq) to screen for associated transcriptomic changes.ResultsThe myopia model was successfully established in FD animals (control eye vs. FD eye, respectively: refraction at day 20, 0.97 ± 0.18 D vs. − 0.13 ± 0.38 D, F = 6.921, P = 0.02; AL difference between day 0 and day 21, 0.29 ± 0.04 mm vs. 0.45 ± 0.03 mm, F = 11.655, P = 0.004). Among the 3 different brimonidine administration methods, intravitreal injection was the most effective in slowing myopia progression, and 4 μg/μL was the most effective among the four different concentrations of brimonidine intravitreal injection tested. The AL and the refraction of the brimonidine intravitreal injection group was significantly shorter or more hyperopic than those of other 2 groups. Four μg/μL produced the smallest difference in AL and spherical equivalent difference values. FD treatment significantly increased the IOP. IOP was significantly lower at 1 day after intravitreal injections which was the lowest in FD eye of intravitreal injection of brimonidine. At day 21, gene expression analyses using RNA-seq showed upregulation of Col1a1 and Mmp2 expression levels by intravitreal brimonidine.ConclusionsAmong the 3 different administration methods, intravitreal injection of brimonidine was the most effective in slowing myopia progression in the FD guinea pig model. Intravitreal brimonidine at 4 μg/μL significantly reduced the development of FD myopia in guinea pigs. Expression levels of the Col1a1 and Mmp2 genes were significantly increased in the retinal tissues of the FD-Inj-Br group.

Canonical Wnt Signaling Drives Myopia Development and Can Be Pharmacologically Modulated.

PurposeThe purpose of this study was to evaluate the role of the canonical Wnt signaling in the development of the myopia.MethodsPlasma from adult patients with myopia, myopic animal models including the adenomatous polyposis coli (APC) gene mutation mouse model, and the form deprivation (FD) induced mouse model of myopia were used. Niclosamide, a canonical Wnt pathway inhibitor, was orally administrated in animal models. Plasma levels of DKK-1 were determined by using enzyme-linked immunosorbent assay. Refraction, vitreous chamber depth (VCD), axial length (AL), and other parameters, were measured at the end of the FD treatment. Canonical Wnt signaling changes were evaluated by Western blot analysis and immunostaining analysis.ResultsPlasma level of Wnt inhibitor DKK-1 was markedly decreased in patients with myopia. Meanwhile, the canonical Wnt pathway was progressively activated during myopia development in mice. Moreover, inhibition of canonical Wnt signaling by niclosamide in mouse models markedly reduced lens thickness (LT), VCD, and AL elongation, resulting in myopia inhibition.ConclusionsDysregulation of canonical Wnt signaling is a characteristic of myopia and targeting Wnt signaling pathways has potential as a therapeutic strategy for myopia.

Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell.

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: −0.91 ± 0.023, atropine: −0.3 ± 0.08, and diacerein: −0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) β1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-β1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

The effect of Wnt/β-catenin pathway on the scleral remolding in the mouse during form deprivation.

Many reports have shown that Wnt/β-Catenin pathway is associated with a variety of diseases, but its role in the pathogenesis of myopia is still unknown. In order to clarify the role of Wnt/β-catenin pathway in the development of form deprivation myopia (FDM), this study investigated the expression of scleral Wls, β-catenin and TCF4 in mice model of form deprivation (FD) myopia. Three parallel experimental groups, including FD, monocular exposure (SC) and binocular exposure (NC) group, were designed to investigate the effects of Wnt/β-Catenin pathway on scleral remodeling mouse during form deprivation in three-week-old C57BL/6 mice. Diopters and axial lengths (AL) in each sample were measured with an infrared eccentric refractometer or spectral-domain optical coherence tomography. The expression of scleral Wls, β-catenin and TCF4 were detected with Western blot. Morphological changes of posterior sclera were observed with a transmission electron microscope (TEM). The above characterization and analysis were performed on the 0th, 7th, 14th, 21st and 28th days, respectively. The difference of diopter and AL between the three groups (SC, NC and FD group) gradually increased with the prolongation of FD time (except AL between SC and NC groups). The changes of diopter and AL gradually increased with the prolongation of FD time. Especially, the diopter and AL will increase sharply after FD lasts for a long time, such as the measurement on the 21st for diopter and 28th days for AL. Most notably, the AL of FD eyes significantly increased after 28days of deprivation. Thinning and disordered arrangement of collagen fibers and a decrease of extracellular matrix were observed with TEM. The expression of scleral Wls, β-catenin and TCF4 increased with age in the NC and SC group. In FD group, they increased significantly on the 7th, 14th and 21st days but decreased on the 28th day. The expression of Wls, β-Catenin and TCF4 to FD were more sensitive indicators than that of diopter and AL. Within the first 7days of FD, the expression of Wls, β-Catenin and TCF4 in sclera increased sharply. With the extension of FD duration, it gradually decreased. It is suggested that the Wnt/β-catenin pathway might be involved in the scleral remodeling induced in FDM mice.

Effect of Scleral Crosslinking Using Multiple Doses of Genipin on Experimental Progressive Myopia in Tree Shrews.

PurposeTo evaluate the effect of scleral crosslinking (SXL) on slowing experimental progressive myopia in tree shrew eyes using sub-Tenon's injections of genipin (GEN) at different concentrations and number of injections.MethodsThree or five sub-Tenon's injections of GEN at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day starting at 18 days of visual experience. Form deprivation (FD) myopia was induced in the injected eye between 24 and 35 days of visual experience; the fellow eye served as control. Tree shrews were randomly assigned to five experimental groups: FD (n = 8); FD + 5 × sham injections (n = 6); FD + 3 × GEN injections at 10 mM (n = 6) and 20 mM (n = 6); and FD + 5 × GEN injections at 20 mM (n = 6). Refractive state and ocular dimensions were measured daily.ResultsCompared with the FD group, the sham-injected group showed a transient effect on slowing vitreous chamber elongation. With increasing GEN dose, SXL had an increasing treatment effect on slowing vitreous chamber elongation and myopia progression. In addition, SXL led to a dose-dependent shortening of the aqueous chamber depth and corneal thickening. Lens thickening was observed in the group with the highest concentration.ConclusionsWe have shown that SXL using GEN can slow axial elongation and myopia progression in tree shrews. The extent of this treatment effect was dose dependent. Several unexpected effects were observed (corneal thickening, decrease of the anterior chamber depth, and lens thickening), which require further optimization of the GEN delivery approach before clinical consideration.Translational RelevanceThe results of this preclinical study suggest that scleral crosslinking using genipin can slow myopia progression.

Comparison of A-Scan ultrasonography and the Lenstar optical biometer in Guinea pig eyes

ObjectiveTo compare the biometric parameters provided by A-scan ultrasonography and the Lenstar optical biometer in guinea pig eyes, including anterior segment depth (ASD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL), and differences of them between treated form deprivation (FD) eyes and untreated fellow eyes after 4 weeks of FD. MethodsThree-week-old guinea pigs (N = 41) were subjected to biometric measurements before monocular FD (baseline) and after a 4-week FD. Statistical analyses including within-subject standard deviation (SDwithin), coefficient of variation (CV), and intraclass correlation coefficient (ICC), used to evaluate repeatability for both the A-scan ultrasonography and the Lenstar individually, and correlation and Bland-Altman analyses were used to assess agreement between the two methods. The absolute values of ASD, LT, VCD and AL as measured by the two devices were compared, and the differences of them between treated (T) and untreated fellow (F) eyes (ΔASD, ΔLT, ΔVCD and ΔAL) (Δ = T-F) were compared between the two devices after 4 weeks of FD. ResultsMeasurements by the Lenstar (ICC: 0.923–0.994) were more repeatable than A-scan ultrasonography (ICC: 0.825–0.870). There was a high correlation for AL (r = 0.851, P < 0.001), a moderate correlation for VCD (r = 0.571, P < 0.001) and LT (r = 0.423, P < 0.001), and a low correlation for ASD (r = 0.230, P < 0.01) between the two devices. The values for ASD, VCD and AL measured by A-scan ultrasonography were larger than those measured by the Lenstar (all, P < 0.001), while LT provided by A-scan ultrasonography was much smaller than that of the Lenstar (P < 0.001). Bland-Altman plots showed poor agreement of absolute values of the four parameters between the two devices. Moreover, there was a high correlation between both methods for ΔAL (r = 0.704, P < 0.001), a moderate correlation for ΔVCD (r = 0.534, P < 0.001) and ΔASD (r = 0.574, P < 0.001), and no correlation for ΔLT (r = 0.303, P = 0.054). The ΔASD, ΔLT, and ΔAL measurements obtained by A-scan ultrasonography were greater than those obtained by the Lenstar (all, P < 0.001), while ΔVCD was mildly smaller using A-scan ultrasonography (P < 0.05). Bland-Altman plots illustrated there is good agreement of ΔAL, ΔVCD, ΔASD, and ΔLT between the two devices. ConclusionsThe Lenstar exhibited better repeatability and provided smaller measurements for AL, VCD and ASD than A-scan ultrasonography. Furthermore, a high correlation and a good agreement for the ΔAL was observed between the two devices after a period of FD. In summary, the two devices cannot replace each other directly to obtain absolute values of ASD, LT, VCD and AL, but the Lenstar still can serve as an option in measuring ΔAL between eyes in guinea pig myopia model.

A Multi-Modality Treatment Approach in Vision Therapy for a Patient with Form Deprivation Adult Strabismic Amblyopia and Nystagmus: A Case Report

Background: Amblyopia is characterised by visual impairment along with compromised binocular visual function. Form deprivation amblyopia is a result of opaque media which results in obstruction of light. This obstruction of light prevents visual development. It is has traditionally been managed at early stage of life through occlusion therapy. Case Summary: A 29-year old male presented to us, diagnosed with form deprivation adult strabismic amblyopia and nystagmus. Anterior segment evaluation showed pseudophakia in both eyes, and posterior segment was within normal limits. Stereopsis was absent. In-office vision therapy and homebased vision therapy was undertaken, which included optometric syntonic phototherapy, biofeedback mechanisms to improve nystagmus along with oculomotor skills, monocular fixation in a binocular field (MFBF) and binocular therapies in-office, and Amb-iNet at home. Conclusion: A multi-modality treatment approach in vision therapy is presented, which resulted in improvement of visual acuity, stereopsis and other components of vision for an adult with form deprivation strabismic amblyopia and nystagmus.

A study of retinal nerve fiber layer thickness and other optic nerve head parameters in cases of amblyopia

Introduction: Amblyopia is a disorder of decreased visual acuity and contrast sensitivity, studies in past have shown retinal changes in amblyopic eyes, which was refuted by other studies. Studies in the recent past have reported variable results on retinal nerve fiber layer (RNFL) thickness in amblyopic eyes. Therefore, there is still a gap in present knowledge. This study was conducted to study RNFL thickness and other optic nerve head (ONH) parameters in amblyopic and better fellow eyes. Materials and Methods: A total of 30 diagnosed cases of amblyopia (four cases of meridional, 11 cases of anisometropic, three cases of strabismic, eight cases of ammetropic, and four cases of form deprivation amblyopia) were divided into two groups: Group A (amblyopic eyes – 30 eyes) and Group B (better fellow eyes – 30 eyes). All the eyes underwent visual acuity assessment, refraction (under cycloplegia), anterior segment evaluation, and fundus evaluation. All the patients underwent ONH evaluation by Cirrus 500 spectral-domain high-definition optical coherence tomography, before and after occlusion therapy. The ONH parameters studied were average RNFL thickness, rim area, disc area, and cup volume. The data were analyzed using SPSS version 25:00. Results: The RNFL thickness was less in amblyopic eyes as compared to normal fellow eyes, (P = 0.002). There was a positive correlation between RNFL thickness and rim area in both the groups, but it was significant (P = 0.02) in Group A only. No statistically significant difference was found between the rim area, disc area, and cup volume between the two groups. Conclusion: The RNFL thickness was found to be significantly less in amblyopic eyes, also there was a significant positive correlation between RNFL thickness and rim area in Group A (P = 0.02).

Tree shrews do not maintain emmetropia in initially-focused narrow-band cyan light

We asked if emmetropia, achieved in broadband colony lighting, is maintained in narrow-band cyan light that is well focused in the emmetropic eye, but does not allow for guidance from longitudinal chromatic aberrations (LCA) and offers minimal perceptual color cues. In addition, we examined the response to a −5 D lens in this lighting. Seven tree shrews from different litters were initially housed in broad-spectrum colony lighting. At 24 ± 1 days after eye opening (Days of Visual Experience, DVE) they were housed for 11 days in ambient narrow-band cyan light (peak wavelength 505 ± 17 nm) selected because it is in focus in an emmetropic eye. Perceptually, monochromatic light at 505 nm cannot be distinguished from white by tree shrews. While in cyan light, each animal wore a monocular −5 D lens (Cyan −5 D eyes). The fellow eye was the Cyan no-lens eye. Daily awake non-cycloplegic measures were taken with an autorefractor (refractive state) and with optical low-coherence optical interferometry (axial component dimensions). These measures were compared with the values of animals raised in standard colony fluorescent lighting: an untreated group (n = 7), groups with monocular form deprivation (n = 7) or monocular −5 D lens treatment (n = 5), or that experienced 10 days in total darkness (n = 5). Refractive state at the onset of cyan light treatment was low hyperopia, (mean ± SEM) 1.4 ± 0.4 diopters. During treatment, the Cyan no-lens eyes became myopic (−2.9 ± 0.3 D) whereas colony lighting animals remained slightly hyperopic (1.0 ± 0.2 D). Initially, refractions of the Cyan −5 D eyes paralleled the Cyan no-lens eyes. After six days, they gradually became more myopic than the Cyan no-lens eyes; at the end of treatment, the refractions were −5.4 ± 0.3 D, a difference of −2.5 D from the Cyan no-lens eyes. When returned to colony lighting at 35 ± 1 DVE, the no-lens eye refractions rapidly recovered towards emmetropia but, as expected, the refraction of the −5 D eyes remained near −5 D. Vitreous chamber depth in both eyes was consistent with the refractive changes. In narrow-band cyan lighting the emmetropization mechanism did not maintain emmetropia even though the light initially was well focused. We suggest that, as the eyes diverged from emmetropia, there were insufficient LCA cues for the emmetropization mechanism to utilize the developing myopic refractive error in order to guide the eyes back to emmetropia. However, the increased myopia in the Cyan −5 D eyes in the narrow-band light indicates that the emmetropization mechanism nonetheless detected the presence of the lens-induced refractive error and responded with increased axial elongation that partly compensated for the negative-power lens. These data support the conclusion that the emmetropization mechanism cannot maintain emmetropia in narrow-band lighting. The additional myopia produced in eyes with the −5 D lens shows that the emmetropization mechanism responds to multiple defocus-related cues, even under conditions where it is unable to use them to maintain emmetropia.

Corneal proteome and differentially expressed corneal proteins in highly myopic chicks using a label-free SWATH-MS quantification approach

Myopia, or short-sightedness, is a highly prevalent refractive disorder in which the eye’s focal length is too short for its axial dimension in its relaxed state. High myopia is associated with increased risks of blinding ocular complications and abnormal eye shape. In addition to consistent findings on posterior segment anomalies in high myopia (e.g., scleral remodeling), more recent biometric and biomechanical data in myopic humans and animal models also indicate anterior segment anomalies (e.g., corneal biomechanical properties). Because the cornea is the anterior-most ocular tissue, providing essential refractive power and physiological stability, it is important to understand the biochemical signaling pathway during myopia development. This study first aimed to establish the entire chicken corneal proteome. Then, using the classical form deprivation paradigm to induce high myopia in chicks, state-of-the-art bioinformatics technologies were applied to identify eight differentially expressed proteins in the highly myopic cornea. These results provide strong foundation for future corneal research, especially those using chicken as an animal model for myopia development.

RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia

Currently there is no consensus regarding the aetiology of the excessive ocular volume that characterizes high myopia. Thus, we aimed to test whether the gene pathways identified by gene set enrichment analysis of RNA-seq transcriptomics refutes the predictions of the Retinal Ion Driven Efflux (RIDE) hypothesis when applied to the induction of form-deprivation myopia (FDM) and subsequent recovery (post-occluder removal). We found that the induction of profound FDM led to significant suppression in the ligand-gated chloride ion channel transport pathway via suppression of glycine, GABAA and GABAC ionotropic receptors. Post-occluder removal for short term recovery from FDM of 6 h and 24 h, induced significant upregulation of the gene families linked to cone receptor phototransduction, mitochondrial energy, and complement pathways. These findings support a model of form deprivation myopia as a Cl− ion driven adaptive fluid response to the modulation of the visual signal cascade by form deprivation that in turn affects the resultant ionic environment of the outer and inner retinal tissues, axial and vitreal elongation as predicted by the RIDE model. Occluder removal and return to normal light conditions led to return to more normal upregulation of phototransduction, slowed growth rate, refractive recovery and apparent return towards physiological homeostasis.

Co-existence of myopia and amblyopia in a guinea pig model with monocular form deprivation.

BackgroundForm deprivation myopia is a type of ametropia, with identifiable causes in humans, that has been induced in many animals. The age of onset of myopia induced by monocular form deprivation coincides with the period of visual development in guinea pigs. However, visual acuity of form-deprived eyes in guinea pigs is not understood yet. In this study, we investigated whether monocular form deprivation would affect visual acuity in infant guinea pigs by evaluating the development of myopia and amblyopia after monocular form deprivation, and whether form deprivation myopia and amblyopia occurred simultaneously or successively.MethodsTwenty pigmented guinea pigs (2 weeks old) were randomly assigned to two groups: monocularly form-deprived (n=10), in which facemasks modified from latex balloons covered the right eye, and normal controls (n=10). Refraction, axial length, and visual acuity were measured at 4 intervals (after 0, 1, 4, and 8 weeks of form deprivation), using cycloplegic streak retinoscopy, A-scan ultrasonography (with an oscillation frequency of 10 MHz), and sweep visual evoked potentials (sweep VEPs), respectively. Sweep VEPs were performed with correction of the induced myopic refractive error.ResultsLonger deprivation periods resulted in significant refractive errors in form-deprived eyes compared with those in contralateral and normal control eyes; the axial lengths of form-deprived eyes increased significantly after 4 and 8 weeks of form deprivation. These results revealed that myopia was established at 4 weeks. The acuity of form-deprived eyes was unchanged compared to that at the pretreatment time point, while that of contralateral eyes and eyes in normal control guinea pigs improved; there were significant differences between the deprived eyes and the other two open eyes from 1 to 8 weeks of form deprivation, showing that amblyopia was possibly established during 1 week of form deprivation.ConclusionsThis study demonstrated the feasibility of using sweep VEPs to estimate the visual acuity of guinea pigs. Further, our results revealed that amblyopia likely occurred earlier than myopia; amblyopia and myopia coexisted after a long duration of monocular form deprivation in guinea pigs. Understanding this relationship may help provide insights into failures of treatment of amblyopia associated with myopic anisometropia.