Chi-ho To

Selective breeding for susceptibility to myopia reveals a gene-environment interaction

Purpose. To test whether the interanimal variability in susceptibility to visually induced myopia is genetically determined. Methods. Monocular deprivation of sharp vision (DSV) was induced in outbred White Leghorn chicks aged 4 days. After 4 days DSV, myopia susceptibility was quantified by the relative changes in axial length and refraction. Chicks in the extreme tails of the distribution of susceptibility to DSV were kept and paired for breeding (high- and low-susceptibility lines). A second round of selection was then performed. The third generation of chicks, derived from the selected parents, was assessed after either monocular DSV (4 or 10 days) or lens wear. Results. After two rounds of selective breeding, the chicks from the high-susceptibility line developed approximately twice as much myopia in response to 4 days DSV as did those from the low-susceptibility line (P < 0.001). All ocular component dimensions differed significantly (P < 0.001) between the two selected lines, both before treatment and in the responses of the treated eye. When DSV was conducted for 10 days, the relative changes in axial length and refractive error were still significantly different between the high and low lines (P < 0.001). The chicks bred for high or low susceptibility to DSV also showed significantly different responses to minus lens wear, but not to plus lens wear. Additive genetic effects explained ∼50% of the interanimal variability in response to DSV. Conclusions. Genes and environment interact to shape refractive development in chicks.

Graded competing regional myopic and hyperopic defocus produce summated emmetropization set points in chick.

PURPOSEnChicks emmetropize accurately to experimentally induced myopic and hyperopic defocus. The authors investigated the emmetropization response when a specific proportion of the retina was exposed to myopic defocus while the remainder was exposed to (competing) hyperopic defocus.nnnMETHODSnNormal chicks (14-15 days old) were fitted monocularly with a lens-cone device that exposed a specific proportion of the available visual field to a high-contrast grating under 10 diopters (D) of myopic defocus (with accommodation relaxed) in a series of patches. The remainder of the visual field (adjacent patches) viewed a grating under 10 D of hyperopic defocus. Groups of chicks wore a lens-cone device designed to provide a spatial ratio (relative proportion of visual field area) of 100:0, 50:50, 40:60, 33:67, 25:75, or 0:100 myopic versus hyperopic defocus. On-axis ocular refraction and axial ocular component dimensions were assessed after 3 and 6 days of cone wear.nnnRESULTSnInterocular differences in refraction (mean ± SD) at day 6 were as follows: +10.4 ± 2.5 D, +7.6 ± 3.6 D, +5.9 ± 3.7 D, +1.6 ± 2.6 D, -2.4 ± 2.7 D, and -8.9 ± 2.6 D for spatial ratios of 100:0, 50:50, 40:60. 33:67, 25:75, and 0:100 respectively. The corresponding interocular vitreous chamber depths were as follows: -515 ± 135 μm, -447 ± 137 μm, -253 ± 220 μm, -105 ± 252 μm, 230 ± 218 μm, and 592 ± 161 μm. The refraction and biometry results for the 33:67 and 25:75 groups were significantly different from those of the single defocus control groups.nnnCONCLUSIONSnIn chicks, the on-axis emmetropization response was weighted according to the spatial ratio. Thus, as the proportion of retinal area receiving myopic defocus increased relative to that receiving hyperopic defocus, the degree of myopic eye growth was reduced.

Heritability of ocular component dimensions in chickens : genetic variants controlling susceptibility to experimentally induced myopia and pretreatment eye size are distinct

Purpose. To investigate the extent to which shared genetic variants control (1) multiple ocular component dimensions and (2) both normal eye length and susceptibility to visually induced myopic eye growth. Methods. Two laboratory-reared populations of chicks were examined. The first was a three-generation pedigree of White Leghorn (WL) birds used in a selective breeding experiment testing susceptibility to monocular deprivation of sharp vision (DSV). The chicks were assessed before (age, 4 days) and after 4 days of treatment with diffusers. The second was the 10th generation of an advanced intercross line (AIL) derived from a broiler-layer cross (age, 3 weeks). Variance components analysis was used to estimate heritability and to assess the evidence for shared genetic determination. Results. All measured ocular components were moderately or highly heritable (range, 0.36-0.61; all P < 0.001) in both chick populations, and there were strong genetic correlations across the traits, corneal curvature, vitreous chamber depth, and axial length. The genetic correlations between eye size and myopia susceptibility traits were not significantly different from 0. Conclusions. The genetic variants controlling ocular component dimensions in chicks are shared across some ocular traits (corneal curvature, vitreous chamber depth, and axial length) but distinct for others (lens thickness and corneal thickness). The genetic variants controlling susceptibility to visually induced myopia in chicks are different from those controlling normal eye size.

The Effects of Simultaneous Dual Focus Lenses on Refractive Development in Infant Monkeys

PURPOSEnWe investigated the effects of two simultaneously imposed, competing focal planes on refractive development in monkeys.nnnMETHODSnStarting at 3 weeks of age and continuing until 150 ± 4 days of age, rhesus monkeys were reared with binocular dual-focus spectacle lenses. The treatment lenses had central 2-mm zones of zero power and concentric annular zones with alternating powers of +3.0 diopter [D] and plano (pL or 0 D) (n = 7; +3D/pL) or -3.0 D and plano (n = 7; -3D/pL). Retinoscopy, keratometry, and A-scan ultrasonography were performed every 2 weeks throughout the treatment period. For comparison purposes data were obtained from monkeys reared with full field (FF) +3.0 (n = 4) or -3.0 D (n = 5) lenses over both eyes and 33 control animals reared with unrestricted vision.nnnRESULTSnThe +3 D/pL lenses slowed eye growth resulting in hyperopic refractive errors that were similar to those produced by FF+3 D lenses (+3 D/pL = +5.25 D, FF +3 D = +4.63 D; P = 0.32), but significantly more hyperopic than those observed in control monkeys (+2.50 D, P = 0.0001). One -3 D/pL monkey developed compensating axial myopia; however, in the other -3 D/pL monkeys refractive development was dominated by the zero-powered portions of the treatment lenses. The refractive errors for the -3 D/pL monkeys were more hyperopic than those in the FF -3 D monkeys (-3 D/pL = +3.13 D, FF -3D = -1.69 D; P = 0.01), but similar to those in control animals (P = 0.15).nnnCONCLUSIONSnIn the monkeys treated with dual-focus lenses, refractive development was dominated by the more anterior (i.e., relatively myopic) image plane. The results indicate that imposing relative myopic defocus over a large proportion of the retina is an effective means for slowing ocular growth.

Inhibitions of Chloride Transport and Gap Junction Reduce Fluid Flow across the Whole Porcine Ciliary Epithelium

PURPOSEnTo study the effects of chloride transport and gap junction inhibitors on fluid formation across the porcine ciliary epithelium.nnnMETHODSnA complete annulus of porcine iris-ciliary body preparation was mounted onto a modified Ussing type chamber to measure the fluid flow (FF) rate. The potential difference (PD) across the preparation was monitored simultaneously. The effects of several inhibitors on chloride transport and gap junction were studied. These included 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), 5-(N,N-dimethyl)amiloride hydrochloride (DMA), bumetanide, niflumic acid, and heptanol.nnnRESULTSnThe average baseline FF rate was 2.56 +/- 0.07 microL/h per preparation (n = 33). DIDS (0.1 mM) or DMA (0.1 mM) showed no effect on both FF and PD when added to the blood side of the preparation. Bumetanide (0.1 mM), on the blood side, inhibited the FF by 46% and caused a slight depolarization of PD. Heptanol (3.5 mM) depolarized the PD and reduced FF by 45% and 78% through the blood and aqueous sides, respectively. Niflumic acid (1 mM at the aqueous side) also depolarized the PD and significantly inhibited the FF (62%).nnnCONCLUSIONSnThe effects of the chloride transport inhibitors on fluid formation across the porcine iris-ciliary body were comparable to that in previous chloride transport studies. The results indicated that fluid secretion by the isolated porcine ciliary epithelium is mainly driven by chloride transport. However, there may be other unidentified ion movements that drive residual FF after chloride transport is inhibited.

The Effects of the Relative Strength of Simultaneous Competing Defocus Signals on Emmetropization in Infant Rhesus Monkeys

Purpose We investigated how the relative surface area devoted to the more positive-powered component in dual-focus lenses influences emmetropization in rhesus monkeys. Methods From 3 to 21 weeks of age, macaques were reared with binocular dual-focus spectacles. The treatment lenses had central 2-mm zones of zero-power and concentric annular zones that had alternating powers of either +3.0 diopters (D) and 0 D (+3 D/pL) or −3.0 D and 0 D (−3 D/pL). The relative widths of the powered and plano zones varied from 50:50 to 18:82 between treatment groups. Refractive status, corneal curvature, and axial dimensions were assessed biweekly throughout the lens-rearing period. Comparison data were obtained from monkeys reared with binocular full-field single-vision lenses (FF+3D, n = 6; FF−3D, n = 10) and from 35 normal controls. Results The median refractive errors for all of the +3 D/pL lens groups were similar to that for the FF+3D group (+4.63 D versus +4.31 D to +5.25 D; P = 0.18–0.96), but significantly more hyperopic than that for controls (+2.44 D; P = 0.0002–0.003). In the −3 D/pL monkeys, refractive development was dominated by the zero-powered portions of the treatment lenses; the −3 D/pL animals (+2.94 D to +3.13 D) were more hyperopic than the FF−3D monkeys (−0.78 D; P = 0.004–0.006), but similar to controls (+2.44 D; P = 0.14–0.22). Conclusions The results demonstrate that even when the more positive-powered zones make up only one-fifth of a dual-focus lens surface area, refractive development is still dominated by relative myopic defocus. Overall, the results emphasize that myopic defocus distributed across the visual field evokes strong signals to slow eye growth in primates.

Isotope-coded protein label based quantitative proteomic analysis reveals significant up-regulation of apolipoprotein A1 and ovotransferrin in the myopic chick vitreous

This study used isotope-coded protein label (ICPL) quantitative proteomics and bioinformatics analysis to examine changes in vitreous protein content and associated pathways during lens-induced eye growth. First, the vitreous protein profile of normal 7-day old chicks was characterized by nano-liquid chromatography electrospray ionization tandem mass spectrometry. A total of 341 unique proteins were identified. Next, myopia and hyperopia were induced in the same chick by attaching −10D lenses to the right eye and +10D lenses to the left eye, for 3 and 7 days. Protein expression in lens-induced ametropic eyes was analyzed using the ICPL approach coupled to LCMS. Four proteins (cystatin, apolipoprotein A1, ovotransferrin, and purpurin) were significantly up-regulated in the vitreous after 3 days of wearing −10D lenses relative to +10D lens contralateral eyes. The differences in protein expression were less pronounced after 7 days when the eyes approached full compensation. In a different group of chicks, western blot confirmed the up-regulation of apolipoprotein A1 and ovotransferrin in the myopic vitreous relative to both contralateral lens-free eyes and hyperopic eyes in separate animals wearing +10D lenses. Bioinformatics analysis suggested oxidative stress and lipid metabolism as pathways involved in compensated ocular elongation.

Short term effects of small incision lenticule extraction surgery on corneal endothelium

AIMnTo assess the effects of small incision lenticule extraction (SMILE) surgery on the corneal endothelium at 1d to 1mo postoperatively.nnnMETHODSnA retrospective, observational study was conducted on 47 patients (47 eyes) who received SMILE surgery. Patients were grouped according to contact lens wear condition. The corneal endothelium was examined preoperatively and at 1d, 1wk and 1mo postoperatively. The corneal endothelium was analyzed for endothelial cell density (ECD), percentage of hexagonal cells, and coefficient of variation (CV) of cell size.nnnRESULTSnThere were no significant decrease in the ECD, percentage of hexagonal cells or increase in CV at 1d, 1wk and 1mo postoperatively (P>0.05). However, there was a small increase of ECD by 2.88% in contact lens wearers (78.26±113.62 cell/mm(2), P<0.05).nnnCONCLUSIONnSMILE has no significant adverse effects on the corneal ECD and morphology during 1mo follow-up time.