Temporal bright light at low frequency retards lens-induced myopia in guinea pigs
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SUBMITTER: Deng B
PROVIDER: S-EPMC10655705 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:PurposeTo investigate the effect of short-wavelength light (SL) on guinea pigs with lens-induced myopia (LIM) and the possible retinoic acid (RA)-related mechanisms.MethodsTwo-week-old guinea pigs (n = 60) with monocular -5D lenses were reared under white light (WL, 580 lux) or SL (440 nm, 500 lux). The left eyes were uncovered as control. Refractive error (RE) and axial length (AL) were measured at baseline, one week, two weeks, and four weeks after intervention. Retinal RA was measured from four guinea pigs after two and four weeks of treatment with HPLC. Two-week-old guinea pigs (n = 52) with monocular -5D lens were fed with either RA or its synthesis inhibitor citral every third day in the morning, and half from each group were reared under WL or SL conditions. RE and AL were recorded at baseline and two and four weeks after intervention. Retinal RA was measured after four weeks of intervention.ResultsAt the end of treatment, guinea pigs exposed to SL were less myopic than to WL (2.06 ± 1.69D vs. -1.00 ± 1.88D), accompanied with shorter AL (P = 0.01) and less retinal RA (P = 0.02). SL reduced retinal RA even after exogenous RA supplementation (P = 0.02) and decelerated LIM compared to WL (1.66 ± 1.03D vs. -3.53 ± 0.90D). Citral slowed ocular growth, leading to similar RE in W+CI and S+CI groups (3.39 ± 1.65D vs. 5.25 ± 0.80D).ConclusionsOverall, SL reduced LIM in guinea pigs, even in those supplemented with oral RA, accompanied by reduced retinal RA levels. Oral RA accelerated eye elongation, but citral equally decelerated eye elongation under SL and WL with no significant retinal RA reduction.
| S-EPMC7817876 | biostudies-literature
Project description:BACKGROUND:Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expression, influencing the development of diseases. RESULTS:To investigate the alterations of microRNA profiling in negative lens-induced myopia (NLIM) guinea pigs and to explore the regulatory role of microRNAs in the occurrence and the development of myopia, we first established the NLIM guinea pig model after induction for 2 weeks. Further, we isolated sclera to purify total messenger RNA (mRNA) in both NLIM and NLIM fellow sclera. Using next generation sequencing technique and bioinformatics analysis, we identified the differentially expressed microRNAs in NLIM guinea pigs, performed the bioinformatics annotation for the differentially expressed microRNAs, and validated the expression of differentially expressed microRNAs. As a result, we successfully established an NLIM model in guinea pigs, identified 27 differentially expressed microRNAs in NLIM guinea pig sclera, including 10 upregulated and 17 downregulated microRNAs. The KEGG annotation showed the main signaling pathways were closely associated with PPAR signaling, pyruvate and propanoate metabolisms, and TGF-beta signaling pathways. CONCLUSIONS:Our findings indicate that the development of myopia is mainly involved in the disorder of metabolic processes in NLIM guinea pigs. The PPAR signaling, pyruvate and propanoate metabolism pathways may play roles in the development of myopia.
| S-EPMC6945544 | biostudies-literature
Project description:Visual environment plays an important role in the occurrence of myopia. We previously showed that the different flashing lights could result in distinct effects on the ocular growth and development of myopia. CCN2 has been reported to regulate various cellular functions and biological processes. However, whether CCN2 signaling was involved in the red flashing light-induced myopia still remains unknown. In the present study, we investigated the effects of the red flashing lights exposure on the refraction and axial length of the eyes in vivo and then evaluated their effects on the expression of CCN2 and TGF- β in sclera tissues. Our data showed that the eyes exposed to the red flashing light became more myopic with a significant increase of the axial length and decrease of the refraction. Both CCN2 and TGF- β , as well as p38 MAPK and PI3K, were highly expressed in the sclera tissues exposed to the red flashing light. Both CCN2 and TGF- β were found to have the same gene expression profile in vivo. In conclusion, our findings found that CCN2 signaling pathway plays an important role in the red flashing light-induced myopia in vivo. Moreover, our study establishes a useful animal model for experimental myopia research.
| S-EPMC3726013 | biostudies-literature
Project description:PurposeThis study aimed to explore the role of the RAS p21 protein activator 1 (RASA1) signaling pathway in apoptosis in choroid tissues from guinea pigs with negative lens-induced myopia (LIM).MethodsBiometric measurements were performed to examine refractive status, ocular parameters, and choroidal thickness (ChT) after myopia induction. The choroidal morphology was observed by hematoxylin and eosin (H&E) staining and TUNEL assay. The expression of the RASA1 signaling pathway at the mRNA and protein levels in choroidal tissues was measured by real-time quantitative PCR (qPCR) and western blot assays.ResultsCompared with the normal control (NC) group, the ocular length of the guinea pigs in LIM increased remarkably, as did the myopic refraction. ChT decreased after myopia induction. H&E staining showed that the thickness and laxity of the choroidal tissues in LIM were strikingly reduced. The number of apoptotic cells in the LIM eyes was increased. Moreover, qPCR and western blot assays showed that the expression levels of both RASA1 and BCL-2-associated agonist of cell death (BAD) were higher in the LIM group than in the NC group, whereas the expression level of B-cell lymphoma 2 (BCL-2) was decreased after 2 weeks of experimental myopia. However, the trend of RASA1, BAD, and BCL-2 expression was reversed after 4 weeks of experimental myopia compared with levels after 2 weeks of experimental myopia.ConclusionsResults showed that the RASA1 signaling pathway is activated in choroid tissues in myopic guinea pigs. Activated RASA1 signaling induces high BAD expression and low BCL-2 expression, which in turn promotes apoptosis and ultimately causes ChT thinning in myopic guinea pigs.
| S-EPMC9578543 | biostudies-literature
Project description:PurposeThis study compared the efficacy of topical 1% atropine applied daily versus every 3 days for controlling myopia progression in guinea pigs.MethodsTo induce myopia, pigmented guinea pigs (New Zealand strain, n = 38) wore monocular -10 D rigid gas-permeable (RGP) contact lenses, which were replaced after 3 weeks with -15 diopter (D) contact lenses. Animals were treated with 1% atropine either daily (Atr-QD; n = 12), or every 3 days (Atr-Q3D; n = 11), or with artificial tears (control group; n = 15). Spherical equivalent refractive error (SER) and axial length (AL) data, as well as retinal and choroidal thickness data were collected weekly.ResultsWhereas mean (±SEM) interocular differences (treated - fellow) in both SER and AL at week 0 (baseline) were similar for all groups, significant differences between the atropine-treated and control groups were evident by week 6 (SER and AL, P < 0.001). The treated eyes of the control group showed relatively more axial elongation and myopia progression than both the Atr-QD and Atr-Q3D groups. Choroidal blood vessel area also decreased over time in the treated eyes of the control group, coupled with choroidal thinning overall, with these changes being attenuated by atropine. Retinal thickness showed a developmental decrease over the treatment period but was unaffected by atropine.ConclusionsFor this defocus-induced guinea pig model of myopia, application of 1% topical atropine slows myopia progression, even when applied every 3 days.Translational relevanceThe results from this study suggest that the frequency of dosing for topical atropine may be reduced from the widely used daily dosing regimen without loss of myopia control efficacy.
| S-EPMC8963669 | biostudies-literature
Project description:PurposeBright light has been shown a powerful inhibitor of myopia development in animal models. We studied which temporal patterns of bright light are the most potent in suppressing deprivation myopia in chickens.MethodsEight-day-old chickens wore diffusers over one eye to induce deprivation myopia. A reference group (n = 8) was kept under office-like illuminance (500 lux) at a 10:14 light:dark cycle. Episodes of bright light (15 000 lux) were super-imposed on this background as follows. Paradigm I: exposure to constant bright light for either 1 hour (n = 5), 2 hours (n = 5), 5 hours (n = 4) or 10 hours (n = 4). Paradigm II: exposure to repeated cycles of bright light with 50% duty cycle and either 60 minutes (n = 7), 30 minutes (n = 8), 15 minutes (n = 6), 7 minutes (n = 7) or 1 minute (n = 7) periods, provided for 10 hours. Refraction and axial length were measured prior to and immediately after the 5-day experiment. Relative changes were analyzed by paired t-tests, and differences among groups were tested by one-way ANOVA.ResultsCompared with the reference group, exposure to continuous bright light for 1 or 2 hours every day had no significant protective effect against deprivation myopia. Inhibition of myopia became significant after 5 hours of bright light exposure but extending the duration to 10 hours did not offer an additional benefit. In comparison, repeated cycles of 1:1 or 7:7 minutes of bright light enhanced the protective effect against myopia and could fully suppress its development.ConclusionsThe protective effect of bright light depends on the exposure duration and, to the intermittent form, the frequency cycle. Compared to the saturation effect of continuous bright light, low frequency cycles of bright light (1:1 min) provided the strongest inhibition effect. However, our quantitative results probably might not be directly translated into humans, but rather need further amendments in clinical studies.
| S-EPMC4216005 | biostudies-literature
Project description: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.
| S-EPMC8278638 | biostudies-literature
Project description:PurposeThe development of myopia in guinea pigs can be inhibited by attenuating scleral hypoxia by increasing choroidal blood perfusion (ChBP). In this study, we reduced ChBP through surgical and pharmacological methods to determine the effect on myopia development. We also determined whether ChBP was reduced by quinpirole, a drug that enhances form-deprivation myopia (FDM).MethodsChBP was reduced in the right eyes of guinea pigs via transection of the temporal ciliary arteries or daily injections of phenylephrine into the inferior peribulbar space for one week during normal ocular growth. Other guinea pigs were subjected to two weeks of monocular FDM-with facemasks, along with daily injections of quinpirole, a dopamine D2 receptor agonist, to enhance the FDM. Changes in refraction, axial length, ChBP, and choroidal thickness (ChT) were measured in both treated and fellow eyes of the treatment and control groups. Scleral hypoxia labeling with pimonidazole adducts and α-smooth muscle actin (α-SMA) protein were also measured.ResultsSurgical and pharmacological reduction of ChBP induced myopia development in the treated eyes. These treatments rendered the scleral hypoxia and increased scleral α-SMA expression. Furthermore, quinpirole injections, which increased the magnitude of myopia, augmented the FDM-associated reductions in ChBP and ChT and increased the levels of scleral hypoxia and α-SMA protein.ConclusionsDecreased ChBP in guinea pigs leads to scleral hypoxia and scleral myofibroblast transdifferentiation with increased α-SMA expression, ultimately resulting in myopia development. In future clinical trials, ChBP reduction can serve as a potential biomarker for early detection of myopia development.
| S-EPMC8740532 | biostudies-literature
Project description:SignificanceDecreased expression of the retinal GJD2 gene messenger RNA (mRNA) and connexin 36 (Cx36) protein in the guinea pig negative lens-induced myopia (LIM) model suggests their involvement in local retinal circuits regulating eye growth.PurposePrevious studies suggest that the GJD2 gene and Cx36 protein encoded by the GJD2 gene play important roles in retinal signaling pathways and eye development. The aim of this study was to investigate the changes in GJD2 mRNA and Cx36 protein expression in the guinea pig lens-induced myopia model.MethodsFour-week-old guinea pigs were randomly divided into two groups. Animals in the experimental group were fitted with monocular -10 D lenses; and animals in the control group, with monocular plano lenses. Biometric measurements, including the spherical equivalent refractive error and axial length, were monitored. Animals were killed after 0, 1, 2, and 3 weeks of treatment, and their retinas were isolated. Retinal GJD2 mRNA and Cx36 protein expression levels were assessed by quantitative real-time polymerase chain reaction and Western blot analysis, respectively.ResultsSpherical equivalent refractive error values indicated that negative lens-treated eyes became significantly more myopic than plano lens-treated eyes (P = .001), consistent with their longer axial lengths compared with those of control eyes. Both GJD2 mRNA and Cx36 protein expression levels were decreased in the retinas of negative lens-treated eyes compared with levels in the retinas of plano lens-treated eyes, although there were differences in the timing; GJD2 mRNA, levels were significantly decreased after 1 and 2 weeks of treatment (P = .01 and P = .004, respectively), whereas Cx36 protein expression was significantly decreased after only 1 week (P = .01).ConclusionsThat both retinal GJD2 mRNA and Cx36 protein expression levels were decreased after induction of myopia with negative lenses points to retinal circuits involving Cx36 in myopia development in the guinea pig.
| S-EPMC7742206 | biostudies-literature
Project description:The sclera is the target organ of axial elongation during myopia onset and progression. Visualizing the sclera in-vivo is important for monitoring the dynamic changes of the sclera remodeling in experimental myopia. In the present study, three-week-old tricolor guinea pigs were subjected to negative controls (n = 8), monocular negative lens-induced myopia (LIM, n = 10), or combining monocular LIM and intravitreally mTORC1 agonist (MHY1485, 4 µg) injection for inducing high myopia (LIM + MHY1485 group, n = 10) for four weeks. Serial biometric measurements were performed to monitor experimental myopia onset and progression. Swept-source optical coherence tomography (SS-OCT) was performed to measure sclera thickness at the beginning and end of study. The results showed four weeks of LIM and LIM + MHY1485 induced a significant degree of myopia shift, compared to the negative control (Control, -2.04 ± 0.60; LIM - 6.21 ± 0.55; LIM + MHY1485, -9.14 ± 1.11, diopters, P < 0.0001). The cross-sectional SS-OCT showed clear boundaries of the inner and outer boundaries of the sclera. At baseline, the mean sclera thickness was 105.05 ± 5.41 μm. At the end of the study, sclera thickness significantly correlated with axial length (coefficient = -4.49 μm for every 0.1 mm axial length increase, 95%CI: -3.56 to -5.83 μm, P < 0.001) and refractive error (coefficient = -2.77 μm for every 1 diopter myopic shift, 95%CI: -2.06 to -3.47 μm, P < 0.001) among all guinea pigs. Sclera thickness also significantly correlates with choroidal thickness and choroidal vascularity index (%). In conclusion, the present study shows SS-OCT can be used as a non-invasive method to evaluate sclera thickness and monitor myopia progression in the guinea pig model of LIM.
| S-EPMC11874840 | biostudies-literature