Oral crocetin administration suppressed refractive shift and axial elongation in a murine model of lens-induced myopia.
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ABSTRACT:
SUBMITTER: Mori K
PROVIDER: S-EPMC6343000 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
Oral crocetin administration suppressed refractive shift and axial elongation in a murine model of lens-induced myopia.
Mori Kiwako K Kurihara Toshihide T Miyauchi Maki M Ishida Ayako A Jiang Xiaoyan X Ikeda Shin-Ichi SI Torii Hidemasa H Tsubota Kazuo K
Scientific reports 20190122 1
Increased global incidence of myopia necessitates establishment of therapeutic approaches against its progression. To explore agents which may control myopia, we screened 207 types of natural compounds and chemical reagents based on an activity of a myopia suppressive factor, early growth response protein 1 (Egr-1) in vitro. Among the candidates, crocetin showed the highest and dose-dependent activation of Egr-1. For in vivo analysis, experimental myopia was induced in 3-week-old C57BL/6 J mice ...[more]
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Project description:AimsTo compare the value of pre-treatment axial elongation (AE) and changes in refractive sphere (M change) for predicting the success in orthokeratology (ortho-k), in order to better identify suitable candidates for myopia control.MethodsThis study further analysed the data of 66 subjects receiving 7-month ortho-k treatment, following a 7-month observation period, during which single-vision spectacles were worn. Rate of myopia progression was determined by AE and M change and subjects categorised as slow, moderate, or rapid progressors based on these changes. Outcomes of myopia control, based on the AE reduction after ortho-k, were classified as 'ineffectual', 'clinically insignificant', or 'beneficial'.ResultsOf the 20 subjects, initially categorised as slow by AE and, of whom 95% were similarly categorised by M change, none benefitted from ortho-k. In contrast, of the 22 subjects with moderate AE, 77% and 23% displaying slow and moderate M change, respectively, the majority (73%) benefitted from ortho-k lens wear. The 24 subjects with rapid AE were poorly identified by M change, with only 21% correctly categorised. The vast majority of rapid progressors showed significant benefit after ortho-k.ConclusionProgression of AE is a good indicator of subsequent success of ortho-k treatment. Delaying commencement of therapy is prudent for children with slow progression as results indicate that they would be unlikely to benefit from this intervention. As change in refractive error frequently underestimates rapid progression of AE, its value for identifying appropriate candidates for myopia control is poor.
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| S-EPMC10617139 | biostudies-literature
Project description:This report describes development of spherical equivalent refraction (SER) and axial length (AL) in two population-based cohorts of white, European children. Predictive factors for myopic growth were explored. Participants were aged 6-7- (n = 390) and 12-13-years (n = 657) at baseline. SER and AL were assessed at baseline and 3, 6 and 9 years prospectively. Between 6 and 16 years: latent growth mixture modelling identified four SER classes (Persistent Emmetropes-PEMM, Persistent Moderate Hyperopes-PMHYP, Persistent High Hyperopes-PHHYP and Emerging Myopes-EMYO) as optimal to characterise refractive progression and two classes to characterise AL. Between 12 and 22-years: five SER classes (PHHYP, PMHYP, PEMM, Low Progressing Myopes-LPMYO and High Progressing Myopes-HPMYO) and four AL classes were identified. EMYO had significantly longer baseline AL (≥ 23.19 mm) (OR 2.5, CI 1.05-5.97) and at least one myopic parent (OR 6.28, CI 1.01-38.93). More myopic SER at 6-7 years (≤ + 0.19D) signalled risk for earlier myopia onset by 10-years in comparison to baseline SER of those who became myopic by 13 or 16 years (p ≤ 0.02). SER and AL progressed more slowly in myopes aged 12-22-years (- 0.16D, 0.15 mm) compared to 6-16-years (- 0.41D, 0.30 mm). These growth trajectories and risk criteria allow prediction of abnormal myopigenic growth and constitute an important resource for developing and testing anti-myopia interventions.
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Project description:The aim was to examine efficacy and safety after Implantable Collamer Lens (ICL) implantation for correction of myopia et myopic astigmatism.This prospective clinical study included 28 eyes of 16 patients which underwent implantation of ICL for correction of myopia up to -18,00 diopters (D) and myopic astigmatism up to -6,00 D in the Eye Clinic Svjetlost Sarajevo, from January 2013 to January 2016. Uncorrected distance visual acuity (UDVA), spherical equivalent (SE), corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell (EC) density were evaluated at one, six and twelve months. For statistical analysis SPSS for Windows and Microsoft Excel were used.Out of 16 patients, with mean age of 28,21 ± 4,06 years, 12 of them had binocular and 4 of them had monocular procedure. After 12 months mean UDVA was 0,76 ± 0,16 compared to UDVA 0,04 ± 0,03 preoperatively. Mean SE preoperatively was -0,21 ± 0,27 D compared to -9,52 ± 3,69 D preoperatively. At 12 months one eye (3,57%) lost 2 Snellen lines. In this study 8 eyes (28,57%) gained 1 line, 5 eyes gained (17,56%) 2 lines, and 3 eyes (10,72%) gained 3 lines. EC loss was 5,50±4.71% after 12 months. There was no significant change of IOP by the end of 12 months follow up period. One haptic crack was reported as the only intraoperative complication. Three postoperative complications were: two lens rotations and one retinal detachment.Implantation of ICL is an effective and safe method for reducing or correcting myopia and myopic astigmatism.
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Project description:To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA was extracted from individual ocular components including cornea, iris, lens, retina, retinal pigment epithelium (RPE)/choroid, and sclera tissue. The miRNA expression analysis was pooled from three samples and carried out using Agilent Mouse miRNA Microarray (8 × 60 K) miRBase21.0. The expression ratio was calculated, and differentially expressed miRNAs were extracted, using GeneSpring GX 14.5. Myopic induction showed a significant myopic refractive change, axial elongation, and choroidal thinning. Through the comprehensive miRNA analysis, several upregulated miRNAs (56 in cornea tissue, 13 in iris tissue, 6 in lens tissue, 0 in retina tissue, 29 in RPE/choroid tissue, and 30 in sclera tissue) and downregulated miRNAs (7 in cornea tissue, 28 in iris tissue, 17 in lens tissue, 9 in retina tissue, 7 in RPE/choroid tissue, and 40 in sclera tissue) were observed. Overlapping expression changes in miRNAs were also found in different ocular components. Some of this miRNA dysregulation may be functionally involved in refractive myopia shift and axial length elongation.
| S-EPMC6695704 | biostudies-literature
Project description:Myopia, or nearsightedness, is the most common form of refractive abnormality and is characterized by excessive ocular elongation in relation to ocular power. Retinal neurotransmitter signaling, including dopamine, is implicated in myopic ocular growth, but the visual pathways that initiate and sustain myopia remain unclear. Melanopsin-expressing retinal ganglion cells (mRGCs), which detect light, are important for visual function, and have connections with retinal dopamine cells. Here, we investigated how mRGCs influence normal and myopic refractive development using two mutant mouse models: Opn4-/- mice that lack functional melanopsin photopigments and intrinsic mRGC responses but still receive other photoreceptor-mediated input to these cells; and Opn4DTA/DTA mice that lack intrinsic and photoreceptor-mediated mRGC responses due to mRGC cell death. In mice with intact vision or form-deprivation, we measured refractive error, ocular properties including axial length and corneal curvature, and the levels of retinal dopamine and its primary metabolite, L-3,4-dihydroxyphenylalanine (DOPAC). Myopia was measured as a myopic shift, or the difference in refractive error between the form-deprived and contralateral eyes. We found that Opn4-/- mice had altered normal refractive development compared to Opn4+/+ wildtype mice, starting ∼4D more myopic but developing ∼2D greater hyperopia by 16 weeks of age. Consistent with hyperopia at older ages, 16 week-old Opn4-/- mice also had shorter eyes compared to Opn4+/+ mice (3.34 vs 3.42 mm). Opn4DTA/DTA mice, however, were more hyperopic than both Opn4+/+ and Opn4-/- mice across development ending with even shorter axial lengths. Despite these differences, both Opn4-/- and Opn4DTA/DTA mice had ∼2D greater myopic shifts in response to form-deprivation compared to Opn4+/+ mice. Furthermore, when vision was intact, dopamine and DOPAC levels were similar between Opn4-/- and Opn4+/+ mice, but higher in Opn4DTA/DTA mice, which differed with age. However, form-deprivation reduced retinal dopamine and DOAPC by ∼20% in Opn4-/- compared to Opn4+/+ mice but did not affect retinal dopamine and DOPAC in Opn4DTA/DTA mice. Lastly, systemically treating Opn4-/- mice with the dopamine precursor L-DOPA reduced their form-deprivation myopia by half compared to non-treated mice. Collectively our findings show that disruption of retinal melanopsin signaling alters the rate and magnitude of normal refractive development, yields greater susceptibility to form-deprivation myopia, and changes dopamine signaling. Our results suggest that mRGCs participate in the eye's response to myopigenic stimuli, acting partly through dopaminergic mechanisms, and provide a potential therapeutic target underling myopia progression. We conclude that proper mRGC function is necessary for correct refractive development and protection from myopia progression.
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Project description:PurposeEye growth and myopia development in chicks, and some other animal models, can be suppressed by rearing under near-monochromatic, short-wavelength blue light. We aimed to determine whether similar effects could be achieved using glass filters that transmit a broader range of short and middle wavelengths.MethodsOn day 6 or 7 post-hatch, 169 chicks were assigned to one of three monocular lens conditions (-10 D, +10 D, plano) and reared for 7 or 10 days under one of four 201-lux lighting conditions: (1) B410 long-wavelength-filtered light, (2) B460 long-wavelength-filtered light, (3) Y48 short-wavelength-filtered light, or (4) HA50 broadband light.ResultsAt 7 days, B410 (but not B460) long-wavelength-filtered light had significantly inhibited negative lens induced axial growth relative to Y48 short-wavelength-filtered light (mean difference in experimental eye = -0.249 mm; P = 0.006) and HA50 broadband light (mean difference = -0.139 mm; P = 0.038). B410 filters also inhibited the negative lens-induced increase in vitreous chamber depth relative to all other filter conditions. Corresponding changes in refraction did not occur, and biometric measurements in a separate cohort of chicks suggested that the axial dimension changes were transient and not maintained at 10 days.ConclusionsChromatic effects on eye growth can be achieved using filters that transmit a broad range of wavelengths even in the presence of strong cues for myopia development.Translational relevanceBroad-wavelength filters that provide a more "naturalistic" visual experience relative to monochromatic light have potential to alter myopia development, although the effects shown here were modest and transient and require exploration in further species.
| S-EPMC8411858 | biostudies-literature