Publications by authors named "Miaozhen Pan"

17 Publications

  • Page 1 of 1

Dietary ω-3 polyunsaturated fatty acids are protective for myopia.

Proc Natl Acad Sci U S A 2021 Oct;118(43)

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China;

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2104689118DOI Listing
October 2021

Declines in PDE4B activity promote myopia progression through downregulation of scleral collagen expression.

Exp Eye Res 2021 Nov 8;212:108758. Epub 2021 Sep 8.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang, China; Research Unit of Myopia Basic Research and Clinical Prevention and Control, Chinese Academy of Medical Sciences (2019RU025), Wenzhou, Zhejiang, China. Electronic address:

Myopia is the most common cause of a visual refractive error worldwide. Cyclic adenosine monophosphate (cAMP)-linked signaling pathways contribute to the regulation of myopia development, and increases in cAMP accumulation promote myopia progression. To pinpoint the underlying mechanisms by which cAMP modulates myopia progression, we performed scleral transcriptome sequencing analysis in form-deprived mice, a well-established model of myopia development. Form deprivation significantly inhibited the expression levels of genes in the cAMP catabolic pathway. Quantitative real-time polymerase chain reaction analysis validated that the gene expression level of phosphodiesterase 4B (PDE4B), a cAMP hydrolase, was downregulated in form-deprived mouse eyes. Under visually unobstructed conditions, loss of PDE4B function in Pde4b-knockout mice increased the myopic shift in refraction, -3.661 ± 1.071 diopters, more than that in the Pde4b-wildtype littermates (P < 0.05). This suggests that downregulation and inhibition of PDE4B gives rise to myopia. In guinea pigs, subconjunctival injection of rolipram, a selective inhibitor of PDE4, led to myopia in normal eyes, and it also enhanced form-deprivation myopia (FDM). Subconjunctival injection of dibutyryl-cyclic adenosine monophosphate, a cAMP analog, induced only a myopic shift in the normal visually unobstructed eyes, but it did not enhance FDM. As myopia developed, axial elongation occurred during scleral remodeling that was correlated with changes in collagen fibril thickness and distribution. The median collagen fibril diameter in the FDM + rolipram group, 55.09 ± 1.83 nm, was thinner than in the FDM + vehicle group, 59.33 ± 2.06 nm (P = 0.011). Thus, inhibition of PDE4 activity with rolipram thinned the collagen fibril diameter relative to the vehicle treatment in form-deprived eyes. Rolipram also inhibited increases in collagen synthesis induced by TGF-β2 in cultured human scleral fibroblasts. The current results further support a role for PDE enzymes such as PDE4B in the regulation of normal refractive development and myopia because either loss or inhibition of PDE4B function increased myopia and FDM development through declines in the scleral collagen fibril diameter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exer.2021.108758DOI Listing
November 2021

PPARγ modulates refractive development and form deprivation myopia in Guinea pigs.

Exp Eye Res 2021 01 2;202:108332. Epub 2020 Nov 2.

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China; Research Unit of Myopia Basic Research and Clinical Prevention and Control, Chinese Academy of Medical Sciences (2019RU025), China. Electronic address:

Form deprivation myopia (FDM) is characterized by loss of choroidal thickness (ChT), reduced choroidal blood perfusion (ChBP), and consequently scleral hypoxia. In some tissues, changes in levels of peroxisome proliferator-activated receptor γ (PPARγ) expression modulate hypoxia-induced pathological responses. We determined if PPARγ modulates FDM through changes in ChT, ChBP, scleral hypoxia-inducible transcription factor (HIF-1α) that in turn regulate scleral collagen type 1 (COL1) expression levels in guinea pigs. Myopia was induced by occluding one eye, while the fellow eye served as control. They received daily peribulbar injections of either the PPARγ antagonist GW9662, or the GW1929 agonist, with or without ocular occlusion for 4 weeks. Ocular refraction and biometric parameters were estimated at baseline, 2 and 4 weeks post-treatment. ChT and ChBP were measured at the 2- and 4-week time points. Western blot analysis determined the expression levels of scleral HIF-1α and COL1. GW9662 induced a myopic shift in unoccluded eyes. Conversely, GW1929 inhibited FDM progression without affecting the refraction in unoccluded eyes. GW9662 reduced both ChT and ChBP in unoccluded eyes, while GW1929 inhibited their declines in occluded eyes. Scleral HIF-1α expression rose in GW9662-treated unoccluded eyes whereas GW1929 reduced HIF-1α upregulation in occluded eyes. GW9662 downregulated scleral COL1 expression in unoccluded eyes, while GW1929 reduced their decreases in occluded eyes. Therefore, PPARγ modulates collagen expression levels and FDM through an inverse relationship between changes in PPARγ and HIF-1α expression levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exer.2020.108332DOI Listing
January 2021

Opposing Effects of PPARα Agonism and Antagonism on Refractive Development and Form Deprivation Myopia in Guinea Pigs.

Invest Ophthalmol Vis Sci 2018 12;59(15):5803-5815

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: To determine if drug-induced peroxisome proliferator-activated receptor α (PPARα) signal pathway modulation affects refractive development and myopia in guinea pigs.

Methods: Pigmented guinea pigs were randomly divided into normal vision (unoccluded) and form deprivation myopia (FDM) groups. Each group received daily peribulbar injections of either a vehicle or (1) PPARα agonist, GW7647, clofibrate, or bezafibrate or (2) PPARα antagonist, GW6471, for 4 weeks. Baseline and posttreatment refraction and ocular biometric parameters were measured. Immunofluorescent staining of PPARα and two of its downstream readouts, cytosolic malic enzyme 1 (ME1) and apolipoproteinA II (apoA-II), was undertaken in selected scleral sections. Western blot analysis determined collagen type I expression levels.

Results: GW6471 induced a myopic shift in unoccluded eyes, but had no effect on form-deprived eyes. Conversely, GW7647 inhibited FDM progression without altering unoccluded eyes. Bezafibrate and clofibrate had effects on refraction similar to those of GW7647 in unoccluded and form-deprived eyes. GW6471 downregulated collagen type I expression in unoccluded eyes whereas bezafibrate inhibited collagen type I decreases in form-deprived eyes. GW6471 also reduced the density of ME1- and apoA-II-stained cells in unoccluded eyes whereas bezafibrate increased apoA-II-positive cell numbers in form-deprived eyes.

Conclusions: As GW7647 and GW6471 had opposing effects on myopia development, PPARα signaling modulation may be involved in this condition in guinea pigs. Fibrates are potential candidates for treating myopia since they reduced both FDM and the associated axial elongation. Bezafibrate also inhibited form deprivation-induced decreases in scleral collagen type I expression and the density of apoA-II expressing cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.17-22297DOI Listing
December 2018

Dopamine Receptor Subtypes Mediate Opposing Effects on Form Deprivation Myopia in Pigmented Guinea Pigs.

Invest Ophthalmol Vis Sci 2018 09;59(11):4441-4448

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: We reported previously that changes in dopamine receptor (DR) subtype activation modulate spontaneous myopia progression in albino guinea pigs. To determine if DR control of refractive error development is different than in its normal counterpart, we evaluated the contribution of dopaminergic pathways to emmetropization and form deprivation myopia (FDM) progression in pigmented guinea pigs.

Methods: Monocular myopia was induced by unilateral form-deprivation (FD). The effects of agonists of D1R (SKF38393) and D2R (quinpirole), the corresponding antagonists (SCH23390 and sulpiride), and vehicle were tested by peribulbar injection around FD or untreated control eyes. High-performance liquid chromatography with electrochemical detection quantified retinal and vitreous dopamine (DA) and 4-dihydroxyphenylacetic acid (DOPAC) levels. Ocular refraction and axial dimensions were measured using eccentric infrared photoretinoscopy (EIR) and A-scan ultrasonography, respectively, initially and after 2 or 4 weeks of treatment.

Results: After treatment with any of these four agents for 2 weeks, retinal and vitreal DA and DOPAC levels were not significantly different in drug- and vehicle-treated eyes. Neither agonism nor antagonism of D1R or D2R activity affected emmetropization. In contrast, D1R activation by SKF38393 inhibited FDM progression, while D2R activation by quinpirole augmented this response. On the other hand, D2R antagonism with sulpiride slowed FDM progression while D1R antagonism with SCH23390 had no effect.

Conclusions: In pigmented guinea pigs, D1R activation inhibited, whereas D2R activation enhanced, FDM. These results closely mirror previous findings in albino animals and offer further evidence that DA and its cognate receptors affect refractive error regulation in guinea pigs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.17-21574DOI Listing
September 2018

Role of Cyclic Adenosine Monophosphate in Myopic Scleral Remodeling in Guinea Pigs: A Microarray Analysis.

Invest Ophthalmol Vis Sci 2018 08;59(10):4318-4325

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: Myopia induction accompanies increased scleral cyclic adenosine phosphate (cAMP) levels and collagen degradation in mammalian models. We compared the scleral gene expression changes following monocular form deprivation (FD) with those induced by adenylate cyclase activation with forskolin (FSK) in guinea pigs.

Methods: Guinea pigs were assigned to FD, FSK-treated, and age-matched (AM) control groups. FSK was injected monocularly into the inferior palpebral subconjunctiva daily for 4 days. After scleral RNA extraction, a gene microarray scanner and software were used to evaluate the gene expression patterns, followed by pathway analysis using Gene Ontology tools. Quantitative PCR (qPCR) was used to analyze the expression of 10 candidate genes in separate sets of form-deprived, vehicle-injected, and AM animals.

Results: FSK injections differentially regulated 13 collagen subtypes compared to AM and FD groups. FSK also downregulated Acta2 and Tgf-β2 compared to the AM eyes. Collagen subtypes and Acta2 underwent larger downregulation in the FSK group than during FD. FSK differentially regulated Rarb, Rxrg, Fzd5, Ctnnd2, Dkk2, and Dkk3, which have been linked to ocular growth. Only a few genes were differentially expressed between the FD and AM groups. There was 80% agreement in the direction of gene regulation between microarray and qPCR results. No significant differences were identified between vehicle-injected and AM eyes.

Conclusions: Collagen, a major scleral extracellular matrix component, is degraded during myopia. Given that FSK and FD both promote myopia through increased collagen degradation, targeting cAMP signaling pathway genes could suppress myopia development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.17-224685DOI Listing
August 2018

Scleral hypoxia is a target for myopia control.

Proc Natl Acad Sci U S A 2018 07 9;115(30):E7091-E7100. Epub 2018 Jul 9.

School of Optometry and Ophthalmology Wenzhou Medical University, Wenzhou, 325027 Zhejiang, China;

Worldwide, myopia is the leading cause of visual impairment. It results from inappropriate extension of the ocular axis and concomitant declines in scleral strength and thickness caused by extracellular matrix (ECM) remodeling. However, the identities of the initiators and signaling pathways that induce scleral ECM remodeling in myopia are unknown. Here, we used single-cell RNA-sequencing to identify pathways activated in the sclera during myopia development. We found that the hypoxia-signaling, the eIF2-signaling, and mTOR-signaling pathways were activated in murine myopic sclera. Consistent with the role of hypoxic pathways in mouse model of myopia, nearly one third of human myopia risk genes from the genome-wide association study and linkage analyses interact with genes in the hypoxia-inducible factor-1α (HIF-1α)-signaling pathway. Furthermore, experimental myopia selectively induced HIF-1α up-regulation in the myopic sclera of both mice and guinea pigs. Additionally, hypoxia exposure (5% O) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1721443115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064999PMC
July 2018

Prostaglandin F2α Receptor Modulation Affects Eye Development in Guinea Pigs.

Basic Clin Pharmacol Toxicol 2018 Sep 29;123(3):263-270. Epub 2018 May 29.

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcpt.13017DOI Listing
September 2018

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

Sci Rep 2017 06 5;7(1):2777. Epub 2017 Jun 5.

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-03075-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459838PMC
June 2017

Effects of the cycloplegic, cyclopentolate, on measurements of refraction in eyes of a strain of wild-type juvenile guinea pig (Cavia porcellus): a comparative study.

Curr Eye Res 2014 Apr 11;39(4):416-20. Epub 2013 Nov 11.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University , School of Medicine, Shanghai , PR China and.

Objective: To investigate the effect(s) of the cycloplegic, cyclopentolate, on measurements of refraction in eyes of a strain of wild-type guinea pig.

Methods: Both eyes of 13 wild-type juvenile guinea pigs (n=26 eyes) were examined both pre- and post-mydriasis, using streak retinoscopy (SR) and eccentric infrared photoretinoscopy (EIP). On the day of measurement, three SR measurements were taken for each eye at 0900, 1000, 1100, 1400, 1500 and 1600, and three EIP measurements for each eye at 0930, 1030, 1130, 1430, 1530 and 1630. Cyclopentolate hydrochloride (1%) was topically administered three times to each eye at 5-min intervals: 1300, 1305 and 1310.

Results: Repeated measurements made by either method revealed that mydriasis did not significantly affect refractive stability (repeated measures, p>0.05). Depending on the stage of mydriasis, however, there were significant differences in measured refractive changes both SR and EIP (0.27 ± 0.65 D, tSR=-2.095, PSR=0.04 and 0.73 ± 1.06 D, tEIP=-3.494, PEIP=0.002, respectively) measurements.

Conclusions: Cyclopentolate had only limited effects on measurements of refraction, indicating that direct SR or EIP measurements of refraction in this wild-type strain of juvenile guinea pig, without the use of a cycloplegic, yield reliable and stable results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/02713683.2013.845226DOI Listing
April 2014

The role of cGMP in ocular growth and the development of form-deprivation myopia in guinea pigs.

Invest Ophthalmol Vis Sci 2013 Dec 3;54(13):7887-902. Epub 2013 Dec 3.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Purpose: Development of myopia is associated with remodeling of the sclera, a tissue composed principally of collagen. Cyclic guanosine monophosphate (cGMP) regulates collagen synthesis in several organs; therefore, we investigated the effects of soluble guanylyl cyclase (sGC) stimulation and inhibition on refraction and ocular growth in guinea pigs under normal and form-deprived (FD) conditions.

Methods: Retinal and scleral cGMP concentrations were measured in normal and monocularly FD guinea pigs at 2 days, 1 week, and 2 weeks of form deprivation and following 2 days recovery. Stimulation of sGC by BAY41-2272 and inhibition by NS-2028 were achieved by daily subconjunctival injection in normal and FD eyes. Refraction and axial parameters were measured at the commencement, middle, and cessation of the experiment. cGMP levels were also determined at the end of the experiment.

Results: Retinal and scleral cGMP concentrations increased in FD eyes from 2 days to 2 weeks (P ≤ 0.029). Levels decreased after 2 days of recovery (P ≤ 0.003). Daily injections of BAY41-2272 induced a myopic shift (P ≤ 0.001) and ocular elongation (P ≤ 0.01) in normal animals, but did not alter myopia in FD eyes (P > 0.05). In contrast, daily injections of NS-2028 partially reduced myopic shifts (P ≤ 0.012) and ocular elongation (P ≤ 0.015) induced by form deprivation, but did not affect ocular growth and refraction in normal eyes (P > 0.05). Retinal and scleral cGMP levels were increased by BAY41-2272 in normal eyes and decreased by NS-2028 in FD eyes.

Conclusions: Changes in cGMP signaling contribute to myopic development. Thus, cGMP may be a potential therapeutic target for preventing/treating myopia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.13-11999DOI Listing
December 2013

cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia.

PLoS One 2013 12;8(8):e71441. Epub 2013 Aug 12.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP). We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs). Form-deprived myopia (FDM) was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC) activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0071441PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741144PMC
April 2014

The effect of temporal and spatial stimuli on the refractive status of guinea pigs following natural emmetropization.

Invest Ophthalmol Vis Sci 2013 Jan 30;54(1):890-7. Epub 2013 Jan 30.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

Purpose: To understand the visual information essential for maintaining stable refraction after emmetropization, we investigated the effects of spatial and temporal stimuli on the refractive status of guinea pigs.

Methods: Eighty-eight guinea pigs (4 weeks old) were randomly divided into 10 groups. Thirty animals were raised in backgrounds of gray (N = 13), square-wave (N = 9), or sine-wave grating (N = 8). Thirty-one animals were raised in gray backgrounds with three frequencies of flicker: gray-1-Hz (n = 10), gray-6-Hz (n = 12), and gray-20-Hz (n = 9). Eighteen animals were raised in regular cages with different frequencies of flicker (n = 6 respectively in 1-Hz-, 6-Hz-, and 20-Hz-flicker groups). Nine animals were raised in regular cages with no additional stimuli and used as normal controls. Ocular biometry was measured before and after 3 weeks of exposure to the test environments.

Results: Guinea pigs raised in the gray background for 3 weeks developed myopia, -6.1 ± 2.1 diopters (D), whereas those exposed to either sine-wave or square-wave gratings, or raised in regular cages, retained stable refractions. Animals in the gray-6-Hz group developed lower myopia, -2.7 ± 2.7 D, than the gray group not exposed to flicker. Animals stimulated with a range of flickering frequencies in regular cages also developed myopia but to a lower degree, -3.1 to 0.2 D, than those in gray backgrounds, -5.0 to -2.7 D.

Conclusions: Guinea pigs require both spatial and temporal stimuli to maintain stable refractions. The influence of temporal stimuli on refraction varies with the type and amount of spatial information available in the visual environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.11-8064DOI Listing
January 2013

Inhibition of experimental myopia by a dopamine agonist: different effectiveness between form deprivation and hyperopic defocus in guinea pigs.

Mol Vis 2011 31;17:2824-34. Epub 2011 Oct 31.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

Purpose: The dopamine (DA) system in the retina is critical to normal visual development as lack of retinal DA signaling may contribute to myopic development. The involvement of DA in myopic development is complex and may be different between form deprivation and hyperopic defocus. This study evaluated effects of a non-selective DA receptor agonist, apomorphine (APO) on refractive development in guinea pigs treated with form deprivation or hyperopic defocus.

Methods: APO was subconjunctivally injected daily for 11 days in form-deprived (0.025 to 2.5 ng/µl) and defocused (0.025 to 250 ng/µl) eyes. Changes in ocular biometry and retinal concentration of DA and its metabolites (DOPAC) were measured in the 2 animal models to assess the level of DA involvement in each of the models (the less the change, the lower the involvement).

Results: Similar myopic degree was induced in both the deprived and defocused eyes (-4.06 D versus -3.64 D) at 11 days of the experiment. DA and DOPAC levels were reduced in the deprived eyes but did not change significantly in the defocused eyes compared to the fellow and normal control eyes. A subconjunctival injection of APO daily for 11 days at concentrations ranged from 0.025 to 2.5 ng/µl inhibited form deprivation myopia in a concentration-dependent manner. By contrast, the APO treatment ranged from 0.025 to 250 ng/µl did not effectively inhibit the defocus-induced myopia and the associated axial elongation.

Conclusions: DA signaling may play a more critical role in form deprivation myopia than in defocus-induced myopia, raising a question whether the mechanisms of DA signaling are different under these two types of experimental myopia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224832PMC
April 2012

Spontaneous high myopia in one eye will affect the development of form deprivation myopia in the fellow eye.

Curr Eye Res 2011 Jun;36(6):513-21

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

Purpose: Whether there is an interaction between eyes of individual subjects in refractive development is an important issue to guide experimental designs and help understand mechanisms involved in development of refractive errors. This study investigated whether spontaneous high myopia in one eye will affect refractive development of the fellow eye treated with form deprivation.

Methods: Thirty-four guinea pigs were divided into four groups: MD (monocularly form-deprived animals with a pre-treatment anisometropia ≤ 2D, n = 8), anisometropic MD (monocular form deprivation on a relatively hyperopic eye in animals with a pre-treatment anisometropia ≥ 10D, n = 9), normal control (non-form deprivation in animals with a pre-treatment anisometropia ≤ 2D, n = 8), and anisometropic control (non-form deprivation in animals with a pre-treatment anisometropia ≥ 10D, n = 9). All eyes in different groups underwent biometric measurements on days 0, 12, 24, and 36 of the experiment.

Results: High myopia in one eye reduced form deprivation myopia in the fellow treated eye. The change in refraction from 0 to 36 days in the deprived eyes was -3.07D for the MD group, but -1.22D for the anisometropic MD group (-3.07D vs. -1.22D: p = 0.009, independent sample t-test). The amount of vitreous chamber lengthening over the same period in the deprived eyes was 0.19 mm for the MD group, but 0.12 mm for the anisometropic MD group (0.19 mm vs. 0.12 mm: p = 0.038, independent sample t-test). Myopic development in the anisometropic animals is mainly inhibited within the first 12 days compared to normal MD animals.

Conclusions: These results indicate that an interaction in refractive development may exist temporarily between two eyes of a highly anisometropic animal if the visual environment has been changed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/02713683.2011.568660DOI Listing
June 2011

Spontaneous axial myopia and emmetropization in a strain of wild-type guinea pig (Cavia porcellus).

Invest Ophthalmol Vis Sci 2009 Mar 21;50(3):1013-9. Epub 2008 Nov 21.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

Purpose: To describe a wild-type guinea pig strain with an incidence of spontaneous axial myopia, minimal pupil responses, lack of accommodation, and apparently normal spatial vision. Such a strain is of interest because it may permit the exploration of defective emmetropization and mapping of the underlying quantitative trait loci.

Methods: Twenty-eight guinea pigs were selected from 220 animals based on binocular myopia (exceeding -1.50 diopter [D]) or anisometropia (difference between both eyes exceeding 10 D) at 4 weeks of age. Refractions and pupil responses were measured with eccentric infrared photoretinoscopy, corneal curvature by modified conventional keratometer, and axial lengths by A-scan ultrasonography once a week. Twenty-one guinea pigs were raised under a normal 12-hour light/12-hour dark cycle. From a sample of 18 anisometropic guinea pigs, 11 were raised under normal light cycle and 7 were raised in the dark to determine the extent to which visual input guides emmetropization. Spatial vision was tested in an automated optomotor drum.

Results: In 10 guinea pigs with myopia in both eyes, refractive errors ranged from -15.67 D to -1.50 D at 3 weeks with a high interocular correlation (R = 0.82); axial length and corneal curvature grew almost linearly over time. Strikingly, two patterns of recovery were observed in anisometropic guinea pigs: in 12 (67%) anisometropia persisted, and in 6 (33%) it declined over time. These ratios remained similar in dark-reared guinea pigs. Unlike published strains, all guinea pigs of this strain showed weak pupil responses and no signs of accommodation but up to 3 cyc/deg of spatial resolution.

Conclusions: This strain of guinea pigs has spontaneous axial refractive errors that may be genetically or epigenetically determined. Interestingly, it differs from other published strains that show no refractive errors, vivid accommodation, or pupil responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.08-2463DOI Listing
March 2009

The development of the refractive status and ocular growth in C57BL/6 mice.

Invest Ophthalmol Vis Sci 2008 Dec 8;49(12):5208-14. Epub 2008 Aug 8.

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

Purpose: To investigate refraction, corneal curvature, axial components, and the correlations between the refraction and ocular growth during the emmetropization in the C57BL/6 mouse.

Methods: Ten groups of 10 mice underwent ocular measurements at 22 to 102 days after birth. Refraction was measured by photoretinoscopy and corneal radius of curvature (CRC) was measured by keratometry. Corneal thickness (CT), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), retinal thickness (RT), and axial length (AL) were measured by optical coherence tomography (OCT) with focal plane advancement.

Results: Refraction was -1.49 +/- 3.17 diopters (D; mean +/- SD) at day 22 and the highest myopia was at day 25 (-4.61 +/- 2.96 D). The refractive error then increased and reached a hyperopic peak (+9.43 +/- 3.33 D) on day 47. The overall change in refraction was significant from 22 to 102 days (P < 0.05). All measured ocular components changed significantly during the study period except for CT and RT (P > 0.05 for CT and RT; P < 0.05 for others). The CRC, ACD, LT, and AL increased from 22 to 47 days. The increase in ACD, LT, and AL continued after 47 days; however, the CRC increased slowly after this age. The ACD became stable around 67 days and LT and AL at 81 days.

Conclusions: In C57BL/6 mouse eyes, myopia developed early and then the refractive error increased rapidly in the hyperopic direction to reach a peak at around 47 days with the major contributing changes being in axial length and corneal curvature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.07-1545DOI Listing
December 2008
-->