Monocular Form Deprivation Research Articles

Role of Cyclic Adenosine Monophosphate in Myopic Scleral Remodeling in Guinea Pigs: A Microarray Analysis.

Myopia induction accompanies increased scleral cyclic adenosine phosphate (cAMP) levels and collagen degradation in mammalian models. We compared the scleral gene expression changes following monocular form deprivation (FD) with those induced by adenylate cyclase activation with forskolin (FSK) in guinea pigs. Guinea pigs were assigned to FD, FSK-treated, and age-matched (AM) control groups. FSK was injected monocularly into the inferior palpebral subconjunctiva daily for 4 days. After scleral RNA extraction, a gene microarray scanner and software were used to evaluate the gene expression patterns, followed by pathway analysis using Gene Ontology tools. Quantitative PCR (qPCR) was used to analyze the expression of 10 candidate genes in separate sets of form-deprived, vehicle-injected, and AM animals. FSK injections differentially regulated 13 collagen subtypes compared to AM and FD groups. FSK also downregulated Acta2 and Tgf-β2 compared to the AM eyes. Collagen subtypes and Acta2 underwent larger downregulation in the FSK group than during FD. FSK differentially regulated Rarb, Rxrg, Fzd5, Ctnnd2, Dkk2, and Dkk3, which have been linked to ocular growth. Only a few genes were differentially expressed between the FD and AM groups. There was 80% agreement in the direction of gene regulation between microarray and qPCR results. No significant differences were identified between vehicle-injected and AM eyes. Collagen, a major scleral extracellular matrix component, is degraded during myopia. Given that FSK and FD both promote myopia through increased collagen degradation, targeting cAMP signaling pathway genes could suppress myopia development.

Effects of Topical Latanoprost on Intraocular Pressure and Myopia Progression in Young Guinea Pigs.

PurposeTo determine whether latanoprost, a prostaglandin analog proven to be very effective in reducing intraocular pressure (IOP) in humans, can also slow myopia progression in the guinea pig form deprivation (FD) model.MethodsTwo-week-old pigmented guinea pigs underwent monocular FD and daily topical latanoprost (0.005%, n = 10) or artificial tears (control, n = 10) starting 1 week after the initiation of FD, with all treatments continuing for a further 9 weeks. Tonometry, retinoscopy, and high-frequency A-scan ultrasonography were used to monitor IOP, refractive error, and ocular axial dimensions, respectively.ResultsLatanoprost significantly reduced IOP and slowed myopia progression. Mean interocular IOP differences (±SEM) recorded at baseline and week 10 were −0.30 ± 0.51 and 1.80 ± 1.16 mm Hg (P = 0.525) for the control group and 0.07 ± 0.35 and −5.17 ± 0.96 mm Hg (P < 0.001) for the latanoprost group. Equivalent interocular differences for optical axial length at baseline and week 10 were 0.00 ± 0.015 and 0.29 ± 0.04 mm (P < 0.001; control) and 0.02 ± 0.02 and 0.06 ± 0.02 mm (P = 0.202; latanoprost), and for refractive error were +0.025 ± 0.36 and −8.2 ± 0.71 diopter (D) (P < 0.001; control), and −0.15 ± 0.35 and −2.25 ± 0.54 D (P = 0.03; latanoprost).ConclusionsIn the FD guinea pig model, latanoprost significantly reduces the development of myopia. Although further investigations into underlying mechanisms are needed, the results open the exciting possibility of a new line of myopia control therapy.

Observations on the relationship between anisometropia, amblyopia and strabismus

We investigated the potential causal relationships between anisometropia, amblyopia and strabismus, specifically to determine whether either amblyopia or strabismus interfered with emmetropization. We analyzed data from non-human primates that were relevant to the co-existence of anisometropia, amblyopia and strabismus in children. We relied on interocular comparisons of spatial vision and refractive development in animals reared with 1) monocular form deprivation; 2) anisometropia optically imposed by either contact lenses or spectacle lenses; 3) organic amblyopia produced by laser ablation of the fovea; and 4) strabismus that was either optically imposed with prisms or produced by either surgical or pharmacological manipulation of the extraocular muscles. Hyperopic anisometropia imposed early in life produced amblyopia in a dose-dependent manner. However, when potential methodological confounds were taken into account, there was no support for the hypothesis that the presence of amblyopia interferes with emmetropization or promotes hyperopia or that the degree of image degradation determines the direction of eye growth. To the contrary, there was strong evidence that amblyopic eyes were able to detect the presence of a refractive error and alter ocular growth to eliminate the ametropia. On the other hand, early onset strabismus, both optically and surgically imposed, disrupted the emmetropization process producing anisometropia. In surgical strabismus, the deviating eyes were typically more hyperopic than their fellow fixating eyes. The results show that early hyperopic anisometropia is a significant risk factor for amblyopia. Early esotropia can trigger the onset of both anisometropia and amblyopia. However, amblyopia, in isolation, does not pose a significant risk for the development of hyperopia or anisometropia.

Reduced Scleral TIMP-2 Expression Is Associated With Myopia Development: TIMP-2 Supplementation Stabilizes Scleral Biomarkers of Myopia and Limits Myopia Development.

The purpose of this study was to determine the endogenous regulation pattern of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the tree shrew sclera during myopia development and investigate the capacity of exogenous TIMP-2 to inhibit matrix metalloproteinase-2 (MMP-2) in vitro and both scleral collagen degradation and myopia development in vivo. TIMP-2 expression in the sclera during myopia development was assessed using polymerase chain reaction. In vitro TIMP-2 inhibition of MMP-2 was investigated using a gelatinase activity plate assay and zymography. Tree shrews were injected with a collagen precursor before undergoing monocular form deprivation and concurrent daily subconjunctival injections of either TIMP-2 or vehicle to the form-deprived eye. In vivo ocular biometry changes were monitored, and scleral tissue was collected after 12 days and assayed for collagen degradation. The development of myopia was associated with a mean reduction in TIMP-2 mRNA expression after 5 days of form deprivation (P < 0.01). Both activation and activity of MMP-2 were inhibited by TIMP-2 with an IC50 of 10 to 20 and 2 nM, respectively. In vivo exogenous addition of TIMP-2 significantly reduced myopia development (P < 0.01), due to reduced vitreous chamber elongation (P < 0.01). In vivo TIMP-2 treatment also significantly inhibited posterior scleral collagen degradation relative to vehicle-treated eyes (P < 0.01), with levels similar to those in control eyes. Myopia development in mammals is associated with reduced expression of TIMP-2, which contributes to increased degradative activity in the sclera. It follows that replenishment of this TIMP-2 significantly reduced the rate of both scleral collagen degradation and myopia development.

Rasgrf1 mRNA expression in myopic eyes of guinea pigs

BackgroundGenome‐wide association studies of patients have linked the Rasgrf1 gene with myopia. The aim of this study was to investigate the messenger RNA (mRNA) expression of Rasgrf1 in the eyes of guinea pigs with induced myopia.MethodsThe myopia was induced by form deprivation in 24 guinea pigs, while additional 12 animals served as a control. Biometric measurements were used to monitor myopic progression. The animals were sacrificed at two, three and four weeks after beginning of the monocular form deprivation, followed by dissection of the retina, and the sclera, as well as mRNA isolation from both layers. A quantitative reverse transcriptase‐polymerase chain reaction was performed to detect the expression of Rasgrf1.ResultsThe spherical equivalent in eyes subjected to form deprivation differed from the fellow eyes, with measurements of −3.80 ± 0.08 D, −3.96 ± 0.94 D and −4.00 ± 0.94 D at the two‐, three‐ and four‐week times, respectively, significantly more myopia than the inter‐ocular difference in the control group (p < 0.05). The form‐deprived eyes also had a longer axial length compared with the fellow eye: 1.37 ± 0.76-mm, 1.32 ± 0.65-mm and 0.92 ± 0.80-mm at two, three and four weeks, respectively, significantly different from the control group (p < 0.05). In contrast, there was no difference in the corneal curvature, anterior chamber depth or lens thickness between the two eyes at any time (p > 0.05). The increase of Rasgrf1 expression was observed in the sclera, with a fold change of 6.596, 4.379 after three weeks and 6.788, 5.711 after four weeks of treatment, compared with the fellow eyes and the control group, respectively (p < 0.05).ConclusionRasgrf1 up‐regulation was found in the sclera of myopic eyes; however, further investigation is needed to determine whether Rasgrf1 plays a causative role or is a consequence of myopia‐induced scleral remodelling.

Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews.

We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development.

What Do Animal Studies Tell Us about the Mechanism of Myopia-Protection by Light?

: Human studies have provided strong evidence that exposure to time outdoors is protective against the onset of myopia. A causal factor may be that the light levels outdoors (30,000-130,000 lux) are much higher than light levels indoors (typically less than 500 lux). Studies using animal models have found that normal animals exposed to low illuminance levels (50 lux) can develop myopia. The myopia and axial elongation, produced in animals by monocular form deprivation, is reduced by light levels in the 15,000 to 25,000 range. Myopia induced with a negative-power lens seems less affected, perhaps because the lens provides a powerful target for the emmetropization mechanism. Animal studies suggest that raising the light levels may have their effect by increasing retinal dopamine activity, probably via the D2 receptor pathway, altering gene expression in the retina and reducing the signals that produce axial elongation.

Role of Chronic Inflammation in Myopia Progression: Clinical Evidence and Experimental Validation

Prevention and treatment of myopia is an important public problem worldwide. We found a higher incidence of myopia among patients with inflammatory diseases such as type 1 diabetes mellitus (7.9%), uveitis (3.7%), or systemic lupus erythematosus (3.5%) compared to those without inflammatory diseases (p<0.001) using data from children (<18years old) in the National Health Insurance Research database. We then examined the inhibition of myopia by atropine in Syrian hamsters with monocular form deprivation (MFD), an experimental myopia model. We found atropine downregulated inflammation in MFD eyes. The expression levels of c-Fos, nuclear factor κB (NFκB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were upregulated in myopic eyes and downregulated upon treatment with atropine. The relationship between the inflammatory response and myopia was investigated by treating MFD hamsters with the immunosuppressive agent cyclosporine A (CSA) or the inflammatory stimulators lipopolysaccharide (LPS) or peptidoglycan (PGN). Myopia progression was slowed by CSA application but was enhanced by LPS and PGN administration. The levels of c-Fos, NF-κB, IL-6, and TNF-α were upregulated in LPS- and PGN-treated eyes and downregulated by CSA treatment. These findings provide clinical and experimental evidence that inflammation plays a crucial role in the development of myopia.

Effects of groupImetabotropic glutamate receptor on the synaptic transmission efficiency of the neurons in primary visual cortex of monocular form deprivated rats

Background The formation of amblyopia is closely associated with glutamate receptors of visual cortex, and researches determined that the expression of metabolic glutamate receptor 1 (mGluR1) in the visual cortex of amblyopic rats is down-regulated.However, the effect of mGluR1 on synaptic transmission of neurons in the visual cortex is unclear. Objective This study was to investigate the role of mGluR1 in the synaptic transmission efficiency of neurons in the primary visual cortex of monocular form-deprivated rats. Methods Sixteen 14-day-old SD rats were randomly divided into normal control group and form-deprivation group, with 8 rats in each group.The eyelids of the left eyes were sutured to establish the monocular form-deprivation models in the rats of the form-deprivation group, and the visual cortex slices were prepared until 31 days after modeling and incubated in artificial cerebrospinal fluid with 3, 5-dihydroxyphenylglycine (DHPG), LY367385+ DHPG, 2-methyl-6-(phenyl acetylene) pyridine hydrochloride(MPEP)+ DHPG and LY367385+ MPEP+ DHPG, respectively.The field excitatory postsynaptic potential (fEPSP) of neurons in the visual cortex of V1 area was detected by extracellular microelectrode recording.The use and care of the animals followed the statement for the Use of Animals in Ophthalmic and Vision Research. Results The slope value before drug treatment was set as 100%, the fEPSP-slopes of the normal control group and the form-deprivation group were increased to (136.4±17.3)% and (120.7±12.8)% after DHPG induction with significant difference between the two groups (t=2.280; P<0.05). The fEPSP-slopes of the normal control group were (114.9±9.3)% and (112.6±15.3)% after LY367385 and MPEP treatment, and those of the form-deprivation group were (107.3±6.0)% and (110.1±4.1)%, which were significantly lower than those after DHPG induction (normal control group: t=2.641, 2.915; both at P<0.05; form-deprivation group: t=2.410, 2.372; both at P<0.05). The fEPSP-slopes of the normal control group and the form-deprivation group were (104.5±2.2)% and (102.8±14.9)% after LY367385+ MPEP treatment, which were lower than that after DHPG induction (t=3.080, 2.306; both at P<0.05). Conclusions The effect of mGluR1 on the synaptic transmission of neurons in the visual cortex weakens after monocular form-deprivation in rats.Both mGluR1 and mGluR5 participate in the neuronic synaptic transmission on visual cortex area and appear to be equivalent contribution. Key words: Electrophysiology; Excitatory amino acid agonists/pharmacology; Excitatory amino acid antagonists/pharmacology; Phenylacetates/pharmacology; Receptors, metabotropic glutamate/physiology; Visual cortex/growth & development; Neuronic synaptic transmission/drug effect; Form deprivation; Rats, SD

The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews

lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period. The FD eye was randomly selected; the contralateral eye served as an untreated control. The refractive state of both eyes was measured daily, starting just before FD began (day 1); axial component dimensions were measured on day 1 and after eleven days of treatment (day 12). Procedure groups: the myopia (treated eye − control eye refraction) in the FD group was the reference. The sham group only underwent brief daily anesthesia and opening of the conjunctiva to expose the sclera. The puncture group, in addition, had a pipette inserted daily into the vitreous. In four vehicle groups, 5 μL of vehicle was injected daily. The NaCl group received 0.85% NaCl. In the NaCl + ascorbic acid group, 1 mg/mL of ascorbic acid was added. The water group received sterile water. The water + ascorbic acid group received water with ascorbic acid (1 mg/mL). We found that the procedures associated with intravitreal injections (anesthesia, opening of the conjunctiva, and puncture of the sclera) did not significantly affect the development of FDM. However, injecting 5 μL of any of the four vehicle solutions slowed the development of FDM. NaCl had a small effect; myopia development in the last 6 days (−0.15 ± 0.08 D/day) was significantly less than in the FD group (−0.55 ± 0.06 D/day). NaCl + Ascorbic acid further slowed the development of FDM on several treatment days. H2O (−0.09 ± 0.05 D/day) and H2O + ascorbic acid (−0.08 ± 0.05 D/day) both almost completely blocked myopia development. The treated eye vitreous chamber elongation, compared with the control eye, in all groups was consistent with the amount of myopia. When FD continued (days 12–16) without injections in the water and water + ascorbic acid groups, the rate of myopia development quickly increased. Thus, it appears the vehicles affected retinal signaling rather than causing damage. The effect of water and water + ascorbic acid may be due to reduced osmolality or ionic concentration near the tip of the injection pipette. The effect of ascorbic acid, compared to NaCl alone, may be due to its reported dopaminergic activity.

Effects of scleral cross-linking using genipin on the process of form-deprivation myopia in the guinea pig: a randomized controlled experimental study.

BackgroundScleral cross-linking (CXL) is a novel attempt to slow down the axial elongation process in animal eyes. As a natural CXL reagent, genipin would be also effective for the prevention of myopia process. Thus, the present study was designed to evaluate the effects of scleral cross-linking using genipin on the form-deprivation (FD) myopia process of guinea pigs.MethodsTwenty-seven 3-week-old pigmented guinea pigs were randomly divided into three groups. Group A (n = 8) is the untreated control group. Group B (n = 8) is the FD control group, where all eyes were induced with monocular FD for 21 days. In Group C (n = 11), a sub-Tenon injection of 0.10 mL 0.50 % genipin was performed on FD eyes at day 0, 7 and 14 during the 21-day monocular FD. The ocular refraction, axial length, biomechanical test and light and electron microscopy were measured on all eyes to check the efficacy and safety of this scleral CXL technique.ResultsCompared with Group A, significant increases in myopic refractive errors, axial elongation and reductions of scleral fibril diameter and density were observed in the 21-day FD eyes of Group B (P < 0.05). In Group C, the scleral CXL resulted in less myopia and axial elongation as compared with Group B (P < 0.05); a significant thickening of scleral fibrils was found after sub-Tenon injections of genipin; no histological damage on the retina or choroid was observed in Group C at the end of this study.ConclusionsThe FD myopia in guinea pig eyes was effectively blocked by the scleral CXL using sub-Tenon injections of genipin. No histological damage was found on the retina or choroid of these treated eyes. Further studies are needed to examine the long-term efficacy and safety of this CXL technique.Electronic supplementary materialThe online version of this article (doi:10.1186/s12886-015-0086-z) contains supplementary material, which is available to authorized users.

ON pathway mutations increase susceptibility to form-deprivation myopia

The ON pathway mutation in nob mice is associated with altered refractive development, and an increased susceptibility to form-deprivation (FD) myopia. In this study, we used mGluR6-/- mice, another ON pathway mutant, to determine whether the nob phenotype was due to the Nyx mutation or abnormal ON pathway transmission. Refractive development under a normal visual environment for mGluR6-/- and age-matched wild-type (WT) mice was measured every 2 weeks from 4 to 16 weeks of age. The response to monocular FD from 4 weeks of age was measured weekly in a separate cohort of mice. Refraction and ocular biometry were obtained using a photorefractor and optical coherence tomography. Retinas were harvested at 16 weeks, and analyzed for dopamine (DA) and DOPAC using high-performance liquid chromatography. Under normal conditions, mGluR6-/- mice were significantly more myopic than their WT controls (refraction at 12 weeks; WT: 9.40 ± 0.16 D, mGluR6-/-: 6.91 ± 0.38 D). Similar to nob mice, two weeks of FD resulted in a significant myopic shift of −5.57 ± 0.72 D in mGluR6-/- mice compared to −1.66 ± 0.19 D in WT animals. No significant axial length changes were observed with either normal or FD visual conditions. At 16 weeks, mGluR6-/- retinas showed significantly lower DOPAC levels (111.2 ± 33.0 pg/mg) compared to their WT counterparts (197.5 ± 11.2 pg/mg). Retinal DA levels were similar between the different genotypes. Our results indicate that reduced retinal DA metabolism/turnover may be associated with increased susceptibility to myopia in mice with ON pathway defect mutations.

Relationship between monocularly deprivation and amblyopia rats and visual system development

ObjectiveTo explore the changes of lateral geniculate body and visual cortex in monocular strabismus and form deprived amblyopic rat, and visual development plastic stage and visual plasticity in adult rats. MethodsA total of 60 SD rats ages 13 d were randomly divided into A, B, C three groups with 20 in each group, group A was set as the normal control group without any processing, group B was strabismus amblyopic group, using the unilateral extraocular rectus resection to establish the strabismus amblyopia model, group C was monocular form deprivation amblyopia group using unilateral eyelid edge resection + lid suture. At visual developmental early phase (P25), meta phase (P35), late phase (P45) and adult phase (P120), the lateral geniculate body and visual cortex area 17 of five rats in each group were exacted for C-fos Immunocytochemistry. Neuron morphological changes in lateral geniculate body and visual cortex was observed, the positive neurons differences of C-fos expression induced by light stimulation was measured in each group, and the condition of radiation development of P120 amblyopic adult rats was observed. ResultsIn groups B and C, C-fos positive cells were significantly lower than the control group at P25 (P<0.05), there was no statistical difference of C-fos protein positive cells between group B and group A (P>0.05), C-fos protein positive cells level of group B was significantly lower than that of group A (P<0.05). The binoculus C-fos protein positive cells level of groups B and C were significantly higher than that of control group at P35, P45 and P120 with statistically significant differences (P<0.05). ConclusionsThe increasing of C-fos expression in geniculate body and visual cortex neurons of adult amblyopia suggests the visual cortex neurons exist a certain degree of visual plasticity.

Neuronal Projections from V1 to V2 in Amblyopia

The mechanism of amblyopia in children with congenital cataract is not understood fully, but studies in macaques have shown that geniculate synapses are lost in striate cortex (V1). To search for other projection abnormalities in amblyopia, the pathway from V1 to V2 was examined using a triple-label technique in three animals raised with monocular suture. [(3)H]proline was injected into one eye to label the ocular dominance columns. Cholera toxin B subunit conjugated to gold (CTB-Au) was injected into V2 to label V1 projection neurons. Alternate sections were processed for cytochrome oxidase (CO) and CTB-Au, or dipped for autoradiography. Eight fields of CTB-Au-labeled cells in V1 opposite injection sites were plotted in layers 2/3 or 4B. After thin stripe injection, labeled cells were concentrated in CO patches. Despite column shrinkage, cells in deprived and normal columns were equal in size and density in both layers 2/3 and 4B. After pale or thick stripe injection, labeled cells were concentrated in interpatches. Only 23% of projection neurons originated from deprived columns. This reduction exceeded the degree of column shrinkage, a result explained by the fact that column shrinkage causes disproportionate loss of interpatch territory. These data indicate that early monocular form deprivation does not alter the segregation of patch and interpatch pathways to V2 stripes or cause selective loss or atrophy of V1 projection neurons. The effect of shrinkage of geniculocortical afferents in layer 4C following visual deprivation is not amplified further by attenuation of the amblyopic eye's projections from V1 to V2.

Dynamic changes of ocular biometric parameters: a modified form-deprivation myopia model of young guinea pigs.

To evaluate the dynamic ocular biometric changes of a modified form-deprivation myopia model in young guinea pigs. THE ANIMALS WERE RANDOMLY ASSIGNED TO TWO GROUPS: the monocularly deprived facemask group (MDF, with all the right eyes covered, n=24) and the normal control group (free of facemask, n=24). Each group was then equally divided into four subgroups which were followed up for 2, 4, 6 and 8 weeks, respectively. Parameters measured from every eye included refraction, corneal curvature, axial length and the dry weight of sclera at the posterior pole. All the facemasks remained in place during the follow-up. The covered eyes developed myopia with the vitreous chamber lengthening and the dry weight of posterior sclera reduced at each time point compared with the contralateral uncovered (P<0.05 at all time points). The changes had a linear correlation with the deprivation time (P<0.05). There were no significant differences in all the parameters between the uncovered eyes of MDF group and the normal control group (P>0.05 at all time points). Monocular form deprivation with the facemask is highly effective and non-invasive in inducing axial myopia in guinea pigs. The axial myopia is mainly caused by the increased vitreous chamber length and the weakened posterior sclera rigidity. The form-deprivation eye didn't interfere with the natural development of the contralateral eye.

Effects of Brief Daily Periods of Unrestricted Vision during Early Monocular Form Deprivation on Development of Visual Area 2

Providing brief daily periods of unrestricted vision during early monocular form deprivation reduces the depth of amblyopia. To gain insights into the neural basis of the beneficial effects of this treatment, the binocular and monocular response properties of neurons were quantitatively analyzed in visual area 2 (V2) of form-deprived macaque monkeys. Beginning at 3 weeks of age, infant monkeys were deprived of clear vision in one eye for 12 hours every day until 21 weeks of age. They received daily periods of unrestricted vision for 0, 1, 2, or 4 hours during the form-deprivation period. After behavioral testing to measure the depth of the resulting amblyopia, microelectrode-recording experiments were conducted in V2. The ocular dominance imbalance away from the affected eye was reduced in the experimental monkeys and was generally proportional to the reduction in the depth of amblyopia in individual monkeys. There were no interocular differences in the spatial properties of V2 neurons in any subject group. However, the binocular disparity sensitivity of V2 neurons was significantly higher and binocular suppression was lower in monkeys that had unrestricted vision. The decrease in ocular dominance imbalance in V2 was the neuronal change most closely associated with the observed reduction in the depth of amblyopia. The results suggest that the degree to which extrastriate neurons can maintain functional connections with the deprived eye (i.e., reducing undersampling for the affected eye) is the most significant factor associated with the beneficial effects of brief periods of unrestricted vision.

Effects of foveal ablation on the pattern of peripheral refractive errors in normal and form-deprived infant rhesus monkeys (Macaca mulatta).

PURPOSE. The purpose of this study was to determine whether visual signals from the fovea contribute to the changes in the pattern of peripheral refractions associated with form deprivation myopia in monkeys. METHODS. Monocular form-deprivation was produced in 18 rhesus monkeys by securing diffusers in front of their treated eyes between 22 ± 2 and 155 ± 17 days of age. In eight of these form-deprived monkeys, the fovea and most of the perifovea of the treated eye were ablated by laser photocoagulation at the start of the diffuser-rearing period. Each eye's refractive status was measured by retinoscopy along the pupillary axis and at 15° intervals along the horizontal meridian to eccentricities of 45°. Control data were obtained from 12 normal monkeys and five monkeys that had monocular foveal ablations and were subsequently reared with unrestricted vision. RESULTS. Foveal ablation, by itself, did not produce systematic alterations in either the central or peripheral refractive errors of the treated eyes. In addition, foveal ablation did not alter the patterns of peripheral refractions in monkeys with form-deprivation myopia. The patterns of peripheral refractive errors in the two groups of form-deprived monkeys, either with or without foveal ablation, were qualitatively similar (treated eyes: F = 0.31, P = 0.74; anisometropia: F = 0.61, P = 0.59), but significantly different from those found in the normal monkeys (F = 8.46 and 9.38 respectively, P < 0.05). CONCLUSIONS. Central retinal signals do not contribute in an essential way to the alterations in eye shape that occur during the development of vision-induced axial myopia.

Spontaneous High Myopia in One Eye Will Affect the Development of Form Deprivation Myopia in the Fellow Eye

Purpose: Whether there is an interaction between eyes of individual subjects in refractive development is an important issue to guide experimental designs and help understand mechanisms involved in development of refractive errors. This study investigated whether spontaneous high myopia in one eye will affect refractive development of the fellow eye treated with form deprivation.Methods: Thirty-four guinea pigs were divided into four groups: MD (monocularly form-deprived animals with a pre-treatment anisometropia ≤ 2D, n = 8), anisometropic MD (monocular form deprivation on a relatively hyperopic eye in animals with a pre-treatment anisometropia ≥ 10D, n = 9), normal control (non-form deprivation in animals with a pre-treatment anisometropia ≤ 2D, n = 8), and anisometropic control (non-form deprivation in animals with a pre-treatment anisometropia ≥ 10D, n = 9). All eyes in different groups underwent biometric measurements on days 0, 12, 24, and 36 of the experiment.Results: High myopia in one eye reduced form deprivation myopia in the fellow treated eye. The change in refraction from 0 to 36 days in the deprived eyes was -3.07D for the MD group, but -1.22D for the anisometropic MD group (-3.07D vs. -1.22D: p = 0.009, independent sample t-test). The amount of vitreous chamber lengthening over the same period in the deprived eyes was 0.19 mm for the MD group, but 0.12 mm for the anisometropic MD group (0.19 mm vs. 0.12 mm: p = 0.038, independent sample t-test). Myopic development in the anisometropic animals is mainly inhibited within the first 12 days compared to normal MD animals.Conclusions: These results indicate that an interaction in refractive development may exist temporarily between two eyes of a highly anisometropic animal if the visual environment has been changed.

Expressions of cellular retinoic acid binding proteins I and retinoic acid receptor-β in the guinea pig eyes with experimental myopia.

All-trans retinoic acid (RA) is the only extrinsic biochemical candidate known to date that could act as a growth controller, the aim of this study was to investigate the expression cellular retinoic acid binding proteins I (CRABP-I) and retinoic acid receptor-β (RAR-β) in retina of the guinea pig eyes with experimental myopia. Ninety guinea pigs aged 14 days were equally and randomly divided into three groups: form deprivation (FD), -5D lens, and control. The diffusers for FD were white translucent hemispheres, and -5D lenses were used to introduce hyperopic defocus. Refraction was measured with streak retinoscopy after cycloplegia, and axial length was calculated with Cinescan A/B ultrasonography. Retina harvested at different time points were used to measure RA level with HPLC and expressions of cellular retinoic acid binding proteins I (CRABP-I) and RA receptor-β (RAR-β) were assayed with Western blot and Real-time PCR. SPSS13.0 software was used for statistical analysis. Up-regulations of CRABP-I and RAR-β in ocular tissues correlated with changes in the refractive status and growth rate of the guinea pig eye (P<0.05). 14 days of monocular form-deprivation led to -5.14D myopia and a 0.281mm axial elongation; 14 days of monocular defocus produced -3.64D myopia and a 0.163 mm axial elongation. The level of retinal RA started to elevate in 7 days (P<0.05) after visual manipulation in both FD and -5D lens groups and became more prominent by 14 days (P<0.01) . The expressions of CRABP-I and RAR-β increased by 14 days after visual manipulation (P<0.05), the mRNA level of RAR-β, however, increased by 7 days after visual manipulation (P<0.05), which suggested that changes of expressions of CRABP-I and RAR-β might lag behind the change of RA. The levels of CRABP-I and RAR-β were elevated in retina of the guinea pig eye with experimental myopia. During the progression of experimental myopia, the retinal RA level increased rapidly, and there might be a positive feedback between the increase of RA and up-regulation of RAR-β.

Pre‐treatment choroidal thickness is not predictive of susceptibility to form‐deprivation myopia in chickens

Chicks developing experimentally-induced myopia show profound thinning of the choroid. We observed a wide range of choroidal thicknesses in a sample of normal chicks prior to their use in a pedigree-based study of form-deprivation myopia. Hence, we tested whether pre-treatment choroidal thickness predicted susceptibility to myopia. Retinal, choroidal and scleral thickness were measured using A-scan ultrasonography in normal White Leghorn chicks (n= 891) aged 4 days old, and again (n=498) after 4 days of monocular form-deprivation at age 8 days of age. Refractive error was assessed by retinoscopy. Relationships between pre-treatment choroidal thickness and other variables were investigated using general linear models and variance components analysis. Untreated 4 day-old male chicks had choroids approximately 10% thinner than females (p<0.001), but sex explained <2% of the overall variability in choroidal thickness. Axial eye length in these untreated chicks was not significantly associated with choroidal thickness (p=0.25). Moreover, pre-treatment choroidal thickness was not predictive of susceptibility to form-deprivation myopia (p=0.89). Heritability analysis suggested that at least 50% of the variation in pre-treatment choroidal thickness was determined by additive genetic effects (p<0.001). Parental choroidal thickness is the major determinant of choroidal thickness in untreated 4-day old chicks. Despite choroidal thickness potentially being indicative of ongoing emmetropisation to innate refractive errors, in this study it was not predictive of subsequent susceptibility to form-deprivation myopia.