Dynamics of accommodative fatigue in rhesus monkeys and humans

AbstractChanges in accommodative dynamics with repeated accommodation were studied in three anesthetized rhesus monkeys and two conscious humans. Maximum accommodation was centrally stimulated via the Edinger–Westphal nucleus in monkeys with a 4 s on, 4 s off paradigm (4×4) for 17 min, 4×1.5 for 27 min and 2×1 for 16 min. Humans accommodated repeatedly to visual targets (5×5; 5D and 2×2; 6D) for 30 min. In all cases, accommodation was sustained throughout. The anesthetized monkeys showed inter-individual variability in the extent of changes in accommodative dynamics over time while no systematic changes were detected in the human accommodative responses. Little accommodative fatigue was found compared to previous studies which have reported a complete loss of accommodation after 5 min of repeated stimulation in monkeys

Applicability of Infrared Photorefraction for Measurement of Accommodation in Awake-Behaving Normal and Strabismic Monkeys

Purpose: This study was designed to use infrared photorefraction to measure accommodation in awake-behaving normal and strabismic monkeys and describe properties of photorefraction calibrations in these monkeys. Methods: Ophthalmic trial lenses were used to calibrate the slope of pupil vertical pixel intensity profile measurements that were made with a custom-built infrared photorefractor. Day to day variability in photorefraction calibration curves, variability in calibration coefficients due to misalignment of the photorefractor Purkinje image and the center of the pupil, and variability in refractive error due to off-axis measurements were evaluated. Results: The linear range of calibration of the photorefractor was found for ophthalmic lenses ranging from ?1 D to +4 D. Calibration coefficients were different across monkeys tested (two strabismic, one normal) but were similar for each monkey over different experimental days. In both normal and strabismic monkeys, small misalignment of the photorefractor Purkinje image with the center of pupil resulted in only small changes in calibration coefficients, that were not statistically significant (P > 0.05). Off-axis measurement of refractive error was also small in the normal and strabismic monkeys (?1 D to 2 D) as long as the magnitude of misalignment was <10°. Conclusions: Remote infrared photorefraction is suitable for measuring accommodation in awake, behaving normal, and strabismic monkeys. Specific challenges posed by the strabismic monkeys, such as possible misalignment of the photorefractor Purkinje image and the center of the pupil during either calibration or measurement of accommodation, that may arise due to unsteady fixation or small eye movements including nystagmus, results in small changes in measured refractive error

Heterogeneity in Karakoram glacier surges

Many Karakoram glaciers periodically undergo surges during which large volumes of ice and debris are rapidly transported down-glacier, usually at a rate of one to two orders of magnitude greater than during quiescence. Here we identify eight recent surges in the region, and map their surface velocities using cross-correlation feature tracking on optical satellite imagery. In total, we present 44 surface velocity datasets, which show that Karakoram surges are generally short-lived, lasting between 3 and 5 years in most cases, and have rapid build-up and relaxation phases, often lasting less than a year. Peak velocities of up to 2 km a-1 are reached during summer months and the surges tend to diminish during winter months. Otherwise, they do not follow a clearly identifiable pattern. In two of the surges, the peak velocity travels down-ice through time as a wave, which we interpret as a surge front. Three other surges are characterised by high velocities that occur simultaneously across the entire glacier surface and acceleration and deceleration is close to monotonic. There is also no consistent seasonal control on surge initiation or termination. We suggest that the differing styles of surge can be partly accounted for by individual glacier configurations, and that while some characteristics of Karakoram surges are akin to thermally-controlled surges elsewhere (e.g. Svalbard), the dominant surge mechanism remains unclear. We thus propose that these surges represent a spectrum of flow instabilities and the processes controlling their evolution may vary on a glacier by glacier basis

Ostrin L. Accommodative changes in lens diameter in rhesus monkeys. Invest Ophthalmol Vis Sci 2006

PURPOSE. Some debate surrounds the accommodative mechanism in primates, particularly whether the lens equatorial diameter increases or decreases during accommodation. This study has been undertaken to measure the relationship between changes in lens diameter and refraction during accommodation in rhesus monkeys. METHODS. Photorefraction was used to measure accommodation, and goniovideography was used to measure accommodative changes in lens diameter in the iridectomized eyes of two rhesus monkeys. Accommodation was stimulated through the full amplitude available to each eye by stimulation of the Edinger-Westphal nucleus of the brain. Dynamic measurement of refractive changes followed by dynamic measurements of changes in lens diameter for the same stimulus current amplitudes allow the relationship between refraction and lens diameter to be determined. I t is well established that accommodation is a dioptric change in power of the eye to allow the eye to focus at near distances. Several aspects regarding how this optical change occurs are undisputed. The increase in optical power of the eye is attributed to an increase in power of the lens. The optical change in the lens occurs as a consequence of ciliary muscle contraction and results in an increase in the central lens surface curvatures and thickness. RESULTS. It is less well established exactly how the accommodative increase in lens thickness and surface curvatures occur. The accommodative mechanism proposed by Helmholtz 1 suggests that in the unaccommodated state, resting tension on zonular fibers extends from the ciliary body to the capsule around the lens equator. This resting zonular tension and the capsular molding forces hold the lens in a relatively flattened and unaccommodated state. With a contraction of the ciliary muscle, the apex of the ciliary body moves toward the lens equator to release tension on the zonular fibers. Gullstrand 2 and Fincham 3 suggest that when zonular tension is released, the elasticity of the capsule molds the lens into an accommodated form. Fincham 3 suggests that the capsular molding forces cause a decrease in the lens equatorial diameter, an increase in lens axial thickness, and an increase in the lens anterior and posterior surface curvatures. Many studies address the accommodative changes in the ciliary body, lens thickness, and lens surface curvatures. Few of the basic changes that occur in these aspects of the accommodative mechanism are disputed. Because the lens periphery and the equator are generally hidden behind the iris and are relatively inaccessible, it has been more difficult to observe accommodative changes at the lens equator or to study accommodative changes in lens diameter. However, several studies have considered these. Helmholtz 1 infers that because lens axial thickness increases and the lens volume cannot change, the lens equatorial diameter must decrease during accommodation. Grossmann observes in a 26-year-old patient with congenital aniridia that a lens diameter of 11.25 mm in the untreated eye increased to 12.25 mm when subjected to cycloplegia with homatropine and decreased to 10.25 mm with eserine stimulated accommodation. Fincham 3 observed accommodative changes in lens diameter in a 22-year-old patient who sustained traumatic aniridia. Retroilluminated photographs were taken through the cornea of the unaccommodated and accommodated aniridic eye while the contralateral eye viewed far and near (12.5 cm) fixation targets. Superimposed images consistently showed a decrease in lens diameter of 0.45 mm from 10.2 mm to 9.75 mm with accommodation. The upper edge of the lens was covered by the eyelid, but the remaining two thirds of the lens diameter was clearly visible and showed a concentric decrease with accommodation. Wilson 6 used retroillumination infrared videophotography to observe accommodative changes in the lens diameter during accommodation in a 27-year-old patient with ocular albinism. The lens diameter was measured at rest, during voluntary accommodation, and during pharmacologic cycloplegia and showed a 7.44% decrease in lens diameter with accommodation and an increase in lens diameter during cycloplegia. No indication is provided regarding the extent of the accommodative response achieved. Magnetic resonance imaging was used to measure lens diameters in 25 patients and showed that lens diameter decreased by 604 m (6.57%) with accommodation to an 8 D stimulus in the eight youngest subjects (age range, 22-29.2 years; mean age, 25.2 years). 7 Rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys have been widely used to study the primate accommodative mechanism and the progression of presbyopia. The anatomy of the rhesus monkey accommodative structures and the accommodative mechanism are similar to that of humans

Changes in crystalline lens radii of curvature and lens tilt and decentration during dynamic accommodation in rhesus monkeys

12 pages, 7 figures.-- PMID: 18318621 [PubMed]Dynamic changes in crystalline lens radii of curvature and lens tilt and decentration were measured during centrally stimulated accommodation in four iridectomized eyes of two adolescent rhesus monkeys. Phakometry measurements were performed dynamically using a custom-built, video-based, Purkinje-image instrument. Lens anterior and posterior radii were calculated from reflections of paired light sources from the ocular surfaces (Purkinje images PI, PIII, and PIV). Lens tilt and decentration were calculated assuming linearity between Purkinje image positions, eye rotation, lens tilt, and decentration. Because the monkey eyes were iridectomized, Purkinje images were referred to the mid-point of the double first Purkinje image (PI). Mean unaccommodated values of anterior and posterior lens radii of curvature were 11.11 ± 1.58 mm and −6.64 ± 0.62 mm, respectively, and these decreased relatively linearly with accommodation in all eyes, at a rate of 0.48 ± 0.14 mm/D and 0.17 ± 0.03 mm/D for anterior and posterior lens surfaces, respectively. Tilt and decentration did not change significantly with accommodation except for tilt around the horizontal axis, which changed at a rate of 0.147 ± 0.25 deg/D. These results are important to fully characterize accommodation in rhesus monkeys.This research was supported by National Institutes of Health Grant # RO1 EY014651 (AG), Ministerio de Educación y Ciencia, Spain grant # FIS2005-04382 (SM) and predoctoral fellowship # BFM2002-02638 (PR), and EuroHORCs-European Science Foundation EURYI Award (SM).Peer reviewe

Development of an in vitro model to study the biological effects of blinking

Purpose To develop a mechanical model in which a contact lens is swept over ocular surface cells under conditions that mimic the force and speed of the blink, and to investigate the resulting biological changes. Methods A computer controlled mechanical instrument was developed to hold a dish containing 3D cultured stratified human ocular surface epithelial cells, across which an arm bearing a contact lens was swept back and forth repeatedly at a speed and force mimicking the human blink. Cells were subjected to repeated sweep cycles for up to 1 h at a speed of 120 mm/s with or without an applied force of 19.6 mN (to mimic pressure exerted by upper eyelid), after which the cell layer thickness was measured, the cell layer integrity was investigated using fluorescent quantum dots (6 and 13 nm) and the phosphorylation levels of various protein kinases were analyzed by human phospho-kinase arrays. Data for selected kinases were further quantitated by enzyme immunoassays. Results The thickness of the cell layers did not change after exposure to sweep cycles with or without applied force. Quantum dots (6 and 13 nm) were able to penetrate the layers of cells exposed to sweep cycles but not layers of untreated control cells. The phosphorylation levels of HSP27 and JNK1/2/3 increased for cells exposed to sweep cycles with applied force compared to untreated control cells. Conclusions The in vitro mechanical instrument is a useful tool to investigate the effects of blinking on the ocular surface

Influence of Amplitude, Starting Point, and Age on First- and Second-Order Dynamics of Edinger-Westphal–Stimulated Accommodation in Rhesus Monkeys

First- and second-order dynamics of Edinger-Westphal–stimulated accommodation in rhesus monkeys depend on the amplitude but not on the starting point of the response. The disaccommodative peak velocity for a given amplitude is lower in older than in younger monkeys

The effect of interleukin-1 on cytokine gene expression by human corneal epithelial cells

The purpose of this study was to characterize the pattern of cytokine gene expression by human corneal epithelial cells (HCEC) in response to interleukin-1 (IL-1). Primary cultured HCEC (P-HCEC) or SV40 transformed HCEC (SV40-HCEC) were treated for 6 hr with serum-free growth-media alone or with recombinant human IL-1β or IL-1α (10 ng ml−1). 33P labeled cDNA was generated from total RNA, then hybridized to a human cytokine expression array. An autoradiograph was generated for each experimental condition and results analysed semi-quantitatively. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect mRNA for IL-8, growth related oncogene-β (GRO-β), intercellular adhesion molecule (ICAM)-1 and Ephrin A5. P-HCEC and SV40-HCEC demonstrated comparable cytokine profiles. For P-HCEC (n=2) the expression of 35 genes was upregulated or only detectable following IL-1β treatment whereas the expression of nine genes was downregulated or undetectable after IL-1β treatment. In SV40-HCEC (n=3), the expression of 48 genes was upregulated or only detectable following IL-1β treatment and the expression of 10 genes was downregulated or undetectable after IL-1β treatment. Some genes that demonstrated increased expression included cadherin-5, ICAM-1, GRO-α, GRO-β, GRO-γ, Activin A (bA subunit), tumor necrosis factor-α, IL-6, and IL-8. Genes that showed decreased expression included the chemokine receptor—CXCR-4, ciliary neurotrophic factor (CNTF), c-kit ligand, Ephrin A5, G-protein coupled receptor RDC-1 and FGF family FGFR2. Bayesian analysis of the SV40-HCEC data (n=3) revealed the expression of 15 genes that were significantly (p<0·05) differentially regulated. Within these 15 genes, the expression of chemokines (GRO-α, GRO-β, IL-8), fibroblast growth factor 13 and the cytokine IL-6 were the most upregulated, while ephrin A5 and chemokine receptor-4 were the most downregulated. IL-1α treatment (n=1 P-HCEC; n=1 SV40-HCEC) produced results very similar to IL-1β treatment. RT-PCR revealed differential regulation of IL-8, GRO-β, ICAM-1 and ephrin A5 in accordance with gene array data. In conclusion, the data demonstrate that IL-1 treatment of HCEC differentially regulates the expression of other cytokine and related genes, thus adding to the body of evidence that IL-1 is a major mediator of ocular surface inflammatory reactions. Since the expression of a large number of genes can be studied simultaneously, gene array studies such as these offers the advantage of understanding global changes in response to a specific stimulus. Thus our study provides insight in to the ocular surface response in conditions of inflammation and corneal wound healing where the levels of IL-1 are known to be increased

Clinical and Epidemiologic Research Meta-Analysis of Sex Differences in Presbyopia

PURPOSE. Uncorrected presbyopia is a significant cause of visual disability globally. Greater comprehension of the etiology of presbyopia and its contributing factors among medical and vision care providers could lead to changes in correction methods and account for sex differences in near-vision requirements. METHODS. A meta-analysis was performed using nine crosssectional studies that provided sufficient data to compare the prevalence and magnitude of presbyopia among men and women. This analysis was further subdivided into measurement methods to determine what differences in presbyopia might exist between men and women. RESULTS. Studies of presbyopia including sex as a contributing factor were highly heterogenic (P ¼ 0.01) but overall found female sex to be statistically significant in predicting earlier onset for presbyopia with an adjusted confidence interval (CI) using the Shore method of 95% CI [1.02, 1.45]. When limited to studies only measuring accommodative amplitude, female sex was not associated with presbyopia in a fixed effects model with a 95% CI [0.49, 1.07]. CONCLUSIONS. While an association between female sex and presbyopia for subjective measurements (near spectacle prescriptions and add powers) was indicated, measurements of accommodative amplitude show a weak tendency toward the opposite conclusion. This suggests that increased association of presbyopia for women is not due to a physiologic difference in accommodation but rather due to other sex differences, such as tasks performed and viewing distances. Age-based correction nomograms for presbyopia should therefore consider these sex differences when prescribing add powers for near tasks. (Invest Ophthalmol Vis Sci. 2012; 53:3215-3220) DOI:10.1167/iovs.12-9791 I t has been estimated that worldwide more than a billion adults are now affected by presbyopia, the age-related loss of accommodation that blurs near vision due to decreased focusing ability. According to worldwide census data, one third of the population is older than 40, an age when the effects of presbyopia become symptomatic enough that individuals begin using near-vision spectacles. As the global population ages, the prevalence of presbyopia will increase. By 2030, the global population older than 40 is expected to rise to 41%. 1 Although estimates show uncorrected presbyopia as one of the leading causes of disability and worthy of attention as a significant contributor to the global burden of disease, 2 it is commonly overlooked as a major source of disability due to the ease of acquiring spectacle readers in wealthy countries. With age, presbyopia eventually affects everyone but is generally measured and diagnosed only when an individual becomes symptomatic and presents to an eye care provider with need for near-vision correction. Due to the need for trained vision care providers, the burden of presbyopia is greatest among vulnerable populations, with sex, race, ethnicity, climate, rurality, and geographic locations considered to be contributing factors. 2-5 While presbyopia often manifests as a difficulty in reading small text, an inability to see near objects clearly can have a substantial impact on the quality of life regardless of literacy or profession. 3 In 1623, Benito Daza de Valdes noted that &apos;&apos;women with blurred vision [presbyopia] cannot follow the same guidelines as men-they require eyeglasses possessing more degrees because they do more delicate work and because they have weaker vision. &apos;&apos; 6 Recent studies confirm that women are indeed still being prescribed with higher near corrections than men of the same age. 7-12 The reason for this sex disparity is not immediately clear. Daza de Valdes made two different claims: women perform &apos;&apos;more delicate work&apos;&apos; and women have naturally &apos;&apos;weaker vision.&apos;&apos; These claims would imply that there are biological, societal, and environmental components to the need for higher-powered near prescriptions in women. Despite findings supporting the conclusion that women are given higher reading prescriptions than men of equal age, there is often no differentiation made among the biological, social, psychological, and cultural factors that could explain this difference. As illustrated in Loss of focusing ability, an underlying cause of presbyopia, occurs due to a loss of elasticity of the crystalline lens, which makes it less effective at increasing optical power with attempts at accommodation. As the ciliary muscle contracts during accommodation, tension on the zonules decreases, but a larger, stiffer presbyopic lens fails to increase in optical power to the same magnitude as a younger, more pliable crystalline lens