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

Yang, Jinglei; Reinach, Peter S.; Zhang, Sen; Pan, Miaozhen; Sun, Wenfeng; Liu, Bo; Li, Fen; Li, Xiaoqing; Zhao, Aihua; Chen, Tianlu; Wang, Jia; Qu, Jia; Zhou, Xiangtian

doi:10.1038/s41598-017-03075-3

Cited by 31 publications

(27 citation statements)

References 32 publications

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“…Baseline refraction and axial component measurements were not different between the right and left eyes of individual animals in each subgroup ( p > 0.05, paired t ‐test). Furthermore, the refraction and axial component values in the left untreated eyes after 2 and 4 weeks were similar to those previously described . These results show that wild‐type guinea pigs undergo emmetropization in an unobstructed vision environment.…”

Section: Resultssupporting

confidence: 87%

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Prostaglandin F2α Receptor Modulation Affects Eye Development in Guinea Pigs

Yang

Pan

Reinach

et al. 2018

Basic Clin Pharma Tox

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Retinal arachidonic acid (ARA) levels in form-deprived eyes decline in guinea pigs. As prostaglandin F2α (PGF2α) is an ARA metabolite and endogenous agonist of prostaglandin F receptor (FP), we have been suggested that down-regulation of PGF2α-FP receptor signalling pathway contributes to myopia onset. To test this hypothesis, this study determines whether: (i) retinal PGF2α levels decline during the development of form deprivation myopia (FDM) in guinea pigs; (ii) FP receptor agonism and antagonism alter emmetropization and myopia development. Pigmented guinea pigs were randomly assigned to normal vision and form-deprived groups. Ultraperformance liquid chromatography coupled with a mass spectrometer (UPLC-MS) measured retinal PGF2α levels 2 weeks after form deprivation (FD). The selective FP agonist, latanoprost acid (LAT) and its corresponding antagonist, AL8810, were peribulbarly injected into each group. An eccentric infrared photorefractor (EIR) monitored refraction. A-scan ultrasonography measured axial elongation (AL) and vitreous chamber depth (VCD). Tonometry measured the intraocular pressure (IOP). Retinal PGF2α levels declined in form-deprived eyes compared to those in normal eyes. Neither LAT nor AL8810 affected IOP with or without FD. On the other hand, after 4 weeks of daily 0.5 μg AL8810 treatment, a myopia of -1.99 ± 0.34 dioptre (D) developed, but LAT had no effect on emmetropization in a normal visual environment. Nevertheless, daily 30 μg LAT treatment for 4 weeks inhibited FDM development by 41% (vehicle control: -8.39 ± 0.45 D; LAT: -4.95 ± 0.39 D; two-way anova with repeated measures, p < 0.05). Down-regulation of PGF2α-FP receptor signalling pathway may contribute to myopia onset as retinal PGF2α declined in myopic eyes and antagonism of FP receptor by AL8810 induced a myopic shift in normal vision environment. Meanwhile, up-regulation of this pathway by LAT inhibited FDM development. However, the mechanism underlying LAT-induced FDM inhibition needs further clarification. This uncertainty exists because its inhibition of FDM suggests that LAT strengthens the scleral framework which reduces axial elongation. On the other hand, its IOP-lowering effect is attributed to thinning and weakening the scleral framework in glaucoma treatment.

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Section: Resultssupporting

confidence: 87%

“…We found FD induced a myopic shift in refraction from 2 to 8 weeks of age . Recently, we showed that FD decreased retinal arachidonic acid (ARA) levels in a guinea pig metabolomics study . Such declines are relevant because ARA can be catalysed by cyclooxygenase (COX) to produce prostaglandins including PGF2α .…”

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Prostaglandin F2α Receptor Modulation Affects Eye Development in Guinea Pigs

Yang

Pan

Reinach

et al. 2018

Basic Clin Pharma Tox

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“…Deprivation in Group II did not interfere with the natural development of the contralateral eye, which is consistent with the findings of other researchers, such as Zhao [35]. Yang et al [36] detected retinal metabolic changes in guinea pigs induced by form deprivation myopia. Although these researchers did not directly measure the SOD and MDA levels, the results they reported represented the retinal metabolite levels.…”

Section: Discussionsupporting

confidence: 88%

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

Deng

Zhao

et al. 2020

BMC Ophthalmol

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Background: To study the morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia (FDHM) in guinea pigs and explore the possible mechanisms of FDHM formation. Methods: Forty 3-week-old guinea pigs were randomized into the blank control (Group I, 20 cases) and model groups (20 cases). In the model group, the right eyes of the guinea pigs were sutured for 8 weeks to induce FDHM (Group II) and the left eyes were considered a self-control group (Group III). The refractive errors were measured with retinoscopy. The anterior chamber depth (AC), lens thickness (L), vitreous chamber depth (V) and axial length (AL) were measured using ultrasonometry A. Retinal and scleral morphology and ultrastructural features were observed with light and electron microscopy. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the retina and sclera were detected with a chemical colorimetric assay. Results: After 8 weeks of stitching, the refractive errors of Group II changed from (+ 3.59 ± 0.33) D to (− 7.96 ± 0.55) D, and these values were significantly higher than those of Group I (+ 0.89 ± 0.32) D and Group III (− 0.55 ± 0.49) D (P < 0.05). The vitreous chamber depth (4.12 ± 0.13) mm and axial length (8.93 ± 0.22) mm of Group II were significantly longer than those of Group I [(3.71 ± 0.23) mm and (7.95 ± 0.37) mm, respectively] and Group III [(3.93 ± 0.04) mm and (8.01 ± 0.15) mm, respectively] (P < 0.05). With the prolongation of form deprivation (FD), the retina and scleral tissues showed thinning, the ganglion cell and inner and outer nuclear layers of the retina became decreased, and the arrangement was disordered. In Group II, the SOD activity was significantly lower than that in Group I and Group III; the MDA content was significantly higher than that in Group I and Group III. The differences were statistically significant (P < 0.05). Conclusions: These findings suggested that in the FDHM guinea pigs model, the refractive errors, the vitreous chamber depth, and axial length increased significantly with prolongation of monocular FD time, and morphological structural changes in the retina and sclera were observed. Oxygen free radicals might participate in the formation of FDHM.

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“…Defects in mitochondrial complexes I and III as a result of increased superoxide and other reactive oxygen species production (Adam-Vizi 2005) have also been shown to lead to neurodegeneration and subsequent vision loss (Yu et al 2012). Indeed, this finding is consistent with recently published evidence of increased expression of TCA cycle and mitochondrial metabolism genes following negative-lens wear in chick (Riddell et al 2016) and disruptions to TCA cycle metabolite abundance following FDMI in guinea pig (Yang et al 2017) further cementing the importance of the mitochondrial respiratory electron transport chain machinery in myopia development.…”

Section: Manuscript To Be Reviewedsupporting

confidence: 90%

Peer Review #1 of "Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/ choroid in chick model of form-deprivation myopia (v0.1)"

2018

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RNA sequencing analysis has demonstrated bidirectional changes in metabolism, structural and immune pathways during early induction of defocus induced myopia. Thus, the aim of this study was to investigate whether similar gene pathways are also related to the more excessive axial growth, ultrastructural and elemental microanalytic changes seen during the induction and recovery from form-deprivation myopia (FDM) in chick and predicted by the RIDE model of myopia. Methods Archived genomic transcriptome data from the first 3 days of induction of monocularly occluded form deprived myopia (FDMI) in chicks was obtained from the GEO database (accession # GSE6543) while data from chicks monocularly occluded for 10 days and then given up to 24 hours of normal visual recovery (FDMR) was collected. Gene set enrichment analysis (GSEA) software was used to determine enriched pathways during the induction (FDMI) and recovery (FDMR) from FD. Curated gene-sets were obtained from open access sources. Results: Clusters of significant changes in mitochondrial energy metabolism, neurotransmission, ion channel transport, G protein coupled receptor signalling, complement cascades and neuron structure and growth were identified during the 10 days of induction of profound myopia and found to correlate well with change in axial dimensions. Bile acid and bile salt metabolism pathways (cholesterol/lipid metabolism and sodium channel activation) were significantly upregulated during the first 24 hours of recovery from 10 days of FDM. Conclusions: The gene pathways altered during induction of FDM are similar to those reported in defocus induced myopia and are established indicators of oxidative stress, osmoreguatory and associated structural changes. These findings are also consistent with the choroidal thinning, axial elongation and hyperosmotic ion distribution patterns across the retina and choroid previously reported in FDM and predicted by RIDE.

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

Cited by 31 publications

References 32 publications

Prostaglandin F2α Receptor Modulation Affects Eye Development in Guinea Pigs

Prostaglandin F2α Receptor Modulation Affects Eye Development in Guinea Pigs

Morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia in guinea pigs

Peer Review #1 of "Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/ choroid in chick model of form-deprivation myopia (v0.1)"

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