Dataset Information

Changes in retinal metabolic profiles associated with form deprivation myopia development in guinea pigs.

ABSTRACT: Retinal metabolic changes have been suggested to be associated with myopia development. However, little is known about either their identity or time dependent behavior during this sight compromising process. To address these questions, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) was applied to compare guinea pig retinal metabolite levels in form deprivation (FD) eyes at 3 days and 2 weeks post FD with normal control (NC) eyes. Orthogonal partial least squares (OPLS) models discriminated between time dependent retinal metabolic profiles in the presence and absence of FD. Myopia severity was associated with more metabolic pattern differences in the FD than in the NC eyes. After 3 days of FD, 11 metabolite levels changed and after 2 weeks the number of differences increased to 16. Five metabolites continuously decreased during two weeks of FD. Two-way ANOVA of the changes identified by OPLS indicates that 15 out of the 22 metabolites differences were significant. Taken together, these results suggest that myopia progression is associated with an inverse relationship between increases in glucose accumulation and lipid level decreases in form-deprived guinea pig eyes. Such changes indicate that metabolomic studies are an informative approach to identify time dependent retinal metabolic alterations associated with this disease.

SUBMITTER: Yang J

PROVIDER: S-EPMC5459838 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Changes in retinal metabolic profiles associated with form deprivation myopia development in guinea pigs.

Yang Jinglei J Reinach Peter S PS Zhang Sen S Pan Miaozhen M Sun Wenfeng W Liu Bo B Li Fen F Li Xiaoqing X Zhao Aihua A Chen Tianlu T Jia Wei W Jia Wei W Qu Jia J Zhou Xiangtian X

Scientific reports 20170605 1

Retinal metabolic changes have been suggested to be associated with myopia development. However, little is known about either their identity or time dependent behavior during this sight compromising process. To address these questions, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) was applied to compare guinea pig retinal metabolite levels in form deprivation (FD) eyes at 3 days and 2 weeks post FD with normal control (NC) eyes. Orthogonal partial least squares (OPLS) models di ...[more]

PMID: 28584257

Similar Datasets

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:Juvenile primates develop myopia when their visual experience is degraded by lid fusion. In response to the abnormal visual input, retinal neural networks cause an excessive growth of the postequatorial segment of the eye, but the mechanism underlying this axial elongation is unknown. By combining analysis of gene expression, injection of the thymidine analog 5-bromo-2'-deoxyuridine and immunocytochemistry, we show that the retinal periphery in both juvenile rhesus macaques and green monkeys harbors a population of mitotically active neuroprogenitor cells that proliferate when the visual experience is altered by lid fusion. Furthermore, the number of dividing cells is highly correlated with the axial elongation of the eye and the resulting myopic refractive error. Thus, the retina undergoes active growth during the postnatal development of the primate eye. This growth is modulated by the visual input and accelerates considerably when the eye develops axial myopia. cDNA subtractions, construction of cDNA libraries and differential screening were performed as previously described (Tkatchenko et al, 2000). Two subtractions were carried out resulting in two cDNA libraries. One library was enriched in clones potentially up-regulated in the retina of the closed eye and the other was enriched in cDNAs potentially down-regulated. One thousand clones from each library were analyzed, and 535 differentially-expressed cDNAs were amplified by PCR and spotted onto glass slides coated with poly-L-lysine (five duplicates for each cDNA). The slides were then processed, hybridized with Cy3- and Cy5-labeled complex cDNA probes and washed in 0.2xSSC as described at http://cmgm.stanford.edu/pbrown/protocols/. Two hybridizations with color swap were carried for each monkey. After hybridization, slides were scanned using a GenePix 4000B microarray scanner (Axon Instruments, Union City, CA). The images were acquired and processed using the GenePix Pro 5.1 software package (Axon Instruments). The data obtained were normalized against GAPDH expression level and mean values (the reported values) and P-values (probability associated with a Student's t-test) were calculated for duplicate experiments (n = 10) with color swap using Microsoft Excel. Genes were defined as differentially regulated if P< 0.05. Cluster analysis was performed using the Genesis software package (provided by Alexander Sturn, Graz University of Technology, Austria).

Dataset Information

Changes in retinal metabolic profiles associated with form deprivation myopia development in guinea pigs.

Publications

Changes in retinal metabolic profiles associated with form deprivation myopia development in guinea pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets