Modeling monocular form deprivation in rabbits using a simulated-cataract intraocular lens

AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2) thin films(PSF)with different degrees of opacity as IOL materials were prepared.The light transmission of the PSF-IOL was measured,and its in vitro biosafety was determined by cell counting kit(CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line.Subsequently,the in vivo safety was determined by implanting the PSF-IOL with 10%wt SiO_(2) into the right eyes of New Zealand white rabbits(PSF-IOL group),and compared with two control groups:contralateral comparison group and normal control(NC)group(Contralateral comparison group:the fellow eye;NC group:a group of binocular normal rabbits without intervention).The flash visual-evoked potentials(F-VEPs)were measured to verify amblyopia.RESULTS:PSFs containing 0,2%,and 10%wt SiO_(2) were successfully constructed.The 0 SiO_(2) PSF was transparent,while the 10%wt SiO_(2) PSF was completely opaque.It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro.In vitro,PSF-IOL with 10%wt SiO_(2) was also non-toxic,and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation.Finally,our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia.CONCLUSION:A PSF-IOL that mimics cataracts is created.A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit.It can be developed fast and stable and holds great potential for future study.

Binocular form deprivation influences the visual cortex

a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are considered to play a crucial role in synaptic plasticity in the developing visual cortex. In this study, we established a rat model of binocular form deprivation by suturing the rat binocular eyelids before eye-opening at postnatal day 14. During development, the decay time of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors of normal rats became longer after eye- opening; however, the decay time did not change significantly in binocular form deprivation rats. The peak value in the normal group became gradually larger with age, but there was no significant change in the binocular form deprivation group. These findings indicate that binocular form deprivation influences the properties of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat visual cortex around the end of the critical period, indicating that form stimulation is associated with the experience-dependent modification of neuronal synapses in the visual cortex.

Intravitreal brimonidine inhibits formdeprivation myopia in guinea pigs

Background:The 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.Methods:Three-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(2μg/μL,4μg/μL,20μg/μL,40μg/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.Results:The 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±0.04mm 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 4μg/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.Fourμg/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.Conclusions:Among 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 4μg/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.

Intravitreal brimonidine inhibits formdeprivation myopia in guinea pigs

Background:The 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.Methods:Three-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(2μg/μL,4μg/μL,20μg/μL,40μg/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.Results:The 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±0.04mm 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 4μg/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.Fourμg/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.Conclusions:Among 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 4μg/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.