Dataset Information

Short Wavelength (Blue) Light Is Protective for Lens-Induced Myopia in Guinea Pigs Potentially Through a Retinoic Acid-Related Mechanism.

ABSTRACT:

Purpose

To investigate the effect of short-wavelength light (SL) on guinea pigs with lens-induced myopia (LIM) and the possible retinoic acid (RA)-related mechanisms.

Methods

Two-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.

Results

At 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).

Conclusions

Overall, 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.

SUBMITTER: Yu M

PROVIDER: S-EPMC7817876 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Short Wavelength (Blue) Light Is Protective for Lens-Induced Myopia in Guinea Pigs Potentially Through a Retinoic Acid-Related Mechanism.

Yu Manrong M Liu Wangyuan W Wang Bingjie B Dai Jinhui J

Investigative ophthalmology & visual science 20210101 1

<h4>Purpose</h4>To investigate the effect of short-wavelength light (SL) on guinea pigs with lens-induced myopia (LIM) and the possible retinoic acid (RA)-related mechanisms.<h4>Methods</h4>Two-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 wa ...[more]

PMID: 33475690

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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.

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.

Dataset Information

Short Wavelength (Blue) Light Is Protective for Lens-Induced Myopia in Guinea Pigs Potentially Through a Retinoic Acid-Related Mechanism.

Purpose

Methods

Results

Conclusions

Publications

Short Wavelength (Blue) Light Is Protective for Lens-Induced Myopia in Guinea Pigs Potentially Through a Retinoic Acid-Related Mechanism.

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