Influences of levodopa on expression of N-methyl-D-aspartate receptor-1-subunit in the visual cortex of monocular deprivation rats

AIM: Many studies have demonstrated N-methyl-D-aspartate receptor-1-subunit (NMDAR1) is associated with amblyopia. The effectiveness of levodopa in improving the visual function of the children with amblyopia has also been proved. But the mechanism is undefined. Our study was to explore the possible mechanism. METHODS: Sixty 14-day-old healthy SD rats were randomly divided into 4 groups, including normal group, monocular deprivation group, levodopa group and normal saline group, 15 rats each. We sutured all the rats' unilateral eyelids except normal group to establish the monocular deprivation animal model and raise them in normal sunlight till 45-day-old. NMDAR1 was detected in the visual cortex with immunohistochemistry methods, Western Blot and Real time PCR. LD and NS groups were gavaged with levodopa (40mg/kg) and normal saline for 28 days respectively. NMDAR1 was also detected with the methods above. RESULTS: NMDAR1 in the visual cortex of MD group was less than that of normal group. NMDAR1 in the visual cortex of LD group was more than that of NS group. CONCLUSION: NMDAR1 is associated with the plasticity of visual development. Levodopa may influence the expression of NMDAR1 and improve visual function, and its target may lie in the visual cortex.

AB013.The effects of monocular deprivation on the Pulfrich phenomenon

Background:Short term monocular deprivation allows for the modulation of ocular dominance,such that the previously deprived eye contribution will increase,while that of non-deprived eye will decrease.This study examines the effects of short monocular occlusion on the Pulfrich phenomenon,an illusory perception of a horizontally moving object moving in an elliptical orbit in depth.In addition,we will explore whether the modulation of the Pulfrich effect is produced in the magnocellular pathway or the parvocellular pathway,by comparing two protocols,each designed to activate one pathway at a time.Methods:The stimulus used throughout the experiment is made up of elements defining a cylinder rotating in depth,allowing to measure interocular delay.The task consists of reporting the direction of rotation of the stimulus presented.There are two different stimuli:the P stimulus is composed of small elements oscillating slowly,which stimulates the parvocellular pathway,and the M stimulus which is composed of large elements oscillating rapidly which stimulates the magnocellular pathway.One experimental session consists of pre-patch testing,one hour of patching,and a post-patch testing.Each participant performs four sessions,both stimuli for each eye.Results:The point of subjective equivalence(PSE)is extracted from psychometric functions obtained during pre-testing and post-testing.Following deprivation of the left eye the PSE shifts negatively,whereas deprivation of the right eye shifts the PSE positively on the psychometric function.This indicated that monocular deprivation slows the perceptual processes of the previously patched eye.The amplitude of this effect is larger for the M protocol than it is for the P protocol.Conclusions:Contrary to expectations,results showed that effects of monocular deprivation are not exclusively mediated by contrast gain mechanisms,as suggested by Zhou and colleagues(2014).The amplitude of the differences observed for the M protocole suggest that the plasticity induced by short term deprivation is equally subjected to dynamic components.

AB066. Duration dependent visual plasticity via monocular deprivation

Background:Short-term monocular deprivation has been recently shown to temporarily increase the sensitivity of the patched eye.Many studies have patched subjects for an arbitrary period of 2.5 hours,but for no principled reason.Our goal is to show a relationship,if any,between the length of patching duration and the strength of its effect.Methods:We tested nine subjects with three different patching durations:1-,2-,3-hour.Four of the nine subjects were patched for 5-hour.Monocular deprivation was achieved by the use of a translucent eyepatch.A session included two rounds of baseline testing of interocular eye balance,patching,and post-patching tests.Each post-patching test occurred at 0,3,6,12,24,48,60 and 96 minutes after patching to track the patching effect over time.Every subject performed two sessions per condition.Results:One-hour patching produced a small shift in ocular dominance.A larger shift occurred from 2-hour patching,but 3-hour patching produced a comparable effect to the one measured after 2-hour patching.Conclusions:These results show a saturation of the patching effect beyond 2-hour patching.Hence,we believe that 2-hour patching duration is the optimal duration for eye dominance changes induced by monocular deprivation.

AB012. The effects of monocular deprivation do not accumulate across days in adults with normal vision

Background:We investigate whether changes in visual plasticity induced by monocular deprivation can be maintained across multiple days.It has been known that monocular deprivation strengthens the deprived eye in adults with normal vision for a short period of time(30-60 minutes).This has been shown through a variety of visual tasks such as binocular combination and rivalry.Methods:Ten subjects were recruited and patched for five consecutive days for two hours.We used a binocular phase combination task to measure the subjects’sensory eye balances.We initially measured their baseline of sensory eye balance,patched their dominant eye,and then conducted post-patching measurements at 0,3,6,12,24 and 48 minutes after patching.Results:We performed a 2-way ANOVA(Before vs.after patching×Day);we found that although the effect of monocular deprivation on the deprived eye was significant,F(1,9)=17.32,P=0.002,the effect of Day was not.Conclusions:Hence we found no accumulation of the patching effect across five days in healthy adults.This suggests that the degree of remnant neural plasticity in adult primary visual cortex may be too limited to be exploited therapeutically.

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.

AB016.Cholinergic enhancement reduces the temporary shift in perceptual eye dominance induced by a few hours of monocular occlusion

Background:A few hours of monocular deprivation with a diffuser eye patch temporarily strengthens the contribution of the deprived eye to binocular vision.This shift in favour of the deprived eye is characterized as a form of adult visual plasticity.Studies in animal and human models suggest that neuromodulators can enhance adult brain plasticity in general.Specifically,acetylcholine has been shown to improve certain aspects of visual function and plasticity in adulthood.We investigated whether a single administration of donepezil(a cholinesterase inhibitor)could further augment the temporary shift in perceptual eye dominance that occurs after two hours of monocular patching.Methods:We conducted three experiments to investigate whether donepezil enhances the shift in perceptual eye dominance induced by monocular patching.In each experiment,healthy adults completed two experimental sessions while taking either donepezil(5 mg,oral)or a placebo(lactose)pill.In experiment 1 we patched the non-dominant eye for 2 hours and measured ocular balance with a binocular phase combination task.In experiment 2 we patched for one hour to investigate whether donepezil shortens the amount of time necessary to observe a shift in ocular dominance.In experiment 3 we patched for 2 hours and measured ocular balance with a binocular rivalry task to see if the effect of donepezil was comparable across the two tasks.We calculated AUCs for the shift in perceptual eye dominance across five time points after removing the patch to compare our treatment conditions in each experiment.Results:Donepezil significantly reduces the magnitude and duration of the shift in perceptual eye dominance produced by both 2(P<0.01)and 1 hours(P<0.05)of monocular patching when measuring ocular balance with a binocular phase combination task.Donepezil also reduces the magnitude of the shift in ocular dominance when measuring balance with a binocular rivalry task.Conclusions:Previous studies have demonstrated that cholinergic potentiation enhances adult brain plasticity.Because of this,we hypothesized donepezil would further augment the strength of the deprived eye after patching.Our study demonstrates that enhanced cholinergic potentiation actually interferes with the consolidation of the perceptual eye dominance plasticity induced by several hours of monocular deprivation.These results contribute to the growing evidence that cholinergic potentiation enhances certain forms of adult brain plasticity at the expense of others.

Experience-dependent expression of Nogo-A and Nogo receptor in the developing rat visual cortex

Nogo-A and Nogo receptor （NgR） expression in the visual cortex following a critical developmental period （postnatal days 20-60） has been previously shown. However, little is known regarding Nogo-A and NgR expression between postnatal day 0 and initiation of the critical period. The present study analyzed Nogo-A and NgR expression at four different time points： postnatal day 0 （P0）, before critical period （P14）, during critical period （P28）, and after critical period （P60）. Results showed significantly increased Nogo-A mRNA and protein expression levels in the visual cortex following birth, and expression levels remained steady between P28 and P60. NgR mRNA or protein expression was dramatically upregulated with age and peaked at P14 or P28, respectively, and maintained high expression to P60. In addition, Nogo-A and NgR expression was analyzed in each visual cortex layer in normal developing rats and rats with monocular deprivation. Monocular deprivation decreased Nogo-A and NgR mRNA and protein expression in the rat visual cortex, in particular in layers Ⅱ-Ⅲ and Ⅳ in the visual cortex contralateral to the deprived eye. These findings suggested that Nogo-A and NgR regulated termination of the critical period in experience- dependent visual cortical plasticity.