Predicting non-equilibrium folding behavior of polymer chains using the steepest-entropy-ascent quantum thermodynamic framework.

The steepest-entropy-ascent quantum thermodynamic (SEAQT) framework is used to explore the influence of heating and cooling on polymer chain folding kinetics. The framework predicts how a chain moves from an initial non-equilibrium state to stable equilibrium along a unique thermodynamic path. The thermodynamic state is expressed by occupation probabilities corresponding to the levels of a discrete energy landscape. The landscape is generated using the Replica Exchange Wang-Landau method applied to a polymer chain represented by a sequence of hydrophobic and polar monomers with a simple hydrophobic-polar amino acid model. The chain conformation evolves as energy shifts among the levels of the energy landscape according to the principle of steepest entropy ascent. This principle is implemented via the SEAQT equation of motion. The SEAQT framework has the benefit of providing insight into structural properties under non-equilibrium conditions. Chain conformations during heating and cooling change continuously without sharp transitions in morphology. The changes are more drastic along non-equilibrium paths than along quasi-equilibrium paths. The SEAQT-predicted kinetics are fitted to rates associated with the experimental intensity profiles of cytochrome c protein folding with Rouse dynamics.

Intraocular accommodative movements in monkeys; relationship to presbyopia.

Our goal was to quantify the age-related changes in the dynamic accommodative movements of the vitreous and aqueous humor in iridic, aniridic, phakic and aphakic primate eyes. Six bilaterally iridic and four bilaterally iridectomized rhesus monkeys, ranging in age from 6 to 25 years, received a stimulating electrode in the midbrain Edinger-Westphal nucleus to induce accommodation, measured by a Hartinger coincidence refractometer. One of the four iridectomized monkeys underwent unilateral extracapsular and another monkey underwent intracapsular lens extraction. Eyes were imaged utilizing specialized techniques and contrast agents to resolve intraocular structures. During accommodation the anterior hyaloid membrane and the posterior lens capsule bowed backward. Central vitreous fluid and structures/strands moved posteriorly toward the optic nerve region as peripheral vitreous, attached to the vitreous zonule, was pulled forward by ciliary muscle contraction. Triamcinolone particles injected intravitreally were also observed in the anterior chamber and moved from the anterior chamber toward the cleft of the anterior hyaloid membrane and then further posteriorly into the vitreous-filled cleft between the vitreous zonule and the ciliary body pars plana. These accommodative movements occurred in all eyes, and declined with age. There are statistically significant accommodative movements of various intravitreal structures. The posterior/anterior fluid flow between the anterior chamber and the vitreous compartments during accommodation/disaccommodation represents fluid displacement to allow/facilitate lens thickening. The posterior accommodative movement of central vitreous fluid may result from centripetal compression of the anterior tips of the cistern-like structure attached to the vitreous zonule, and posterior displacement of the central trunk of the cistern during ciliary muscle contraction and centripetal muscle movement. The findings may have implications for presbyopia.

Accommodative movements of the choroid in the optic nerve head region of human eyes, and their relationship to the lens.

The ciliary muscle (CM) powers the accommodative response, and during accommodation the CM pulls the choroid forward in the region of the ora serrata. Our goal was to elucidate the accommodative movements of the choroid in the optic nerve region in humans and to determine whether these movements are related to changes in the lens dimensions that occur with aging, in the unaccommodated and accommodated state. Both eyes of 12 human subjects (aged 18-51 yrs) were studied. Homatropine (1 drop/5%) was used to relax the ciliary muscle (unaccommodated or "resting" eye) and pilocarpine was used to induce the maximum accommodative response (2 drops/4%) (accommodated eye). Images of the fundus and choroid were collected in the region of the optic nerve (ON) via Spectralis OCT (infrared and EDI mode), and choroidal thickness was determined. Ultrasound biomicroscopy (UBM; 50 MHz, 35 MHz) images were collected in the region of the lens/capsule and ciliary body. OCT and UBM images were collected in the resting and accommodated state. The unaccommodated choroidal thickness declined significantly with age (p = 0.0073, r = 0.73) over the entire age range of the subjects studied (18-51 years old). The choroidal thickness was significantly negatively correlated with lens thickness in the accommodated (p = 0.01) and the unaccommodated states (p = 0.005); the thicker the lens the thinner the choroid. Choroid movements around the optic nerve during accommodation were statistically significant; during accommodation the choroid both thinned and moved centrifugally (outward/away from the optic nerve head). The accommodative choroid movements did not decline significantly with age and were not correlated with accommodative amplitude. Measurement of the choroidal thickness is possible with the Spectralis OCT instrument using EDI mode and can be used to determine the accommodative changes in choroidal thickness. The choroidal thickness decreased with age and during accommodation. It may be that age-related choroidal thinning is due to changes in the geometry of the accommodative apparatus to which it is attached (i.e., ciliary muscle/lens complex) such that when the lens is thicker, the choroid is thinner. Accommodative decrease in choroidal thickness and stretch of the retina/choroid may indicate stress/strain forces in the region of the optic nerve during accommodation and may have implications for glaucoma.

A randomised controlled trial of a cognitive skills programme for offenders with mental illness.

BACKGROUND: Interventions for offenders with mental illness have tended to be confined to treatment of illness, with the expectation that symptom reduction will be accompanied by reduced criminal recidivism, but recent evidence suggests that other treatment targets may be more effective against recidivism. AIM: The aim of this study was to examine the effect of a cognitive skills programme (Reasoning and Rehabilitation 2: Short Version for Adults [R&R2]) among offenders with mental illness. Our first hypothesis was that participation in this programme would result in significantly greater improvement in antisocial attitudes than among similar prisoners who did not participate; both groups received "treatment as usual" (TAU). Our second hypothesis was that those receiving R&R2 would show less post-treatment violent or general recidivism than those receiving TAU alone. METHOD: Incarcerated offenders with serious mental illness (N = 101) were randomly assigned to R&R2 or TAU alone. Criminal attitudes and mental state were examined before and after treatment. Violent and non-violent recidivism was measured, on average, 18 months after release. RESULTS: In both intervention and TAU alone trial arms, there were significant pre- to post-treatment changes in criminal attitudes and symptoms or signs of mental disorder. There was no difference between groups in these respects. These pre/post changes were not associated with reductions in recidivism over time, whether or not controlling for baseline risk. CONCLUSIONS: Although there was no demonstrable advantage of R&R2 over TAU alone, non-significant trends towards lower violent recidivism in the R&R2 group and general recidivism in the TAU group suggest that it may be worth repeating the trial in a larger sample with more differentiated control groups.

Subfunctionalization of COX4 paralogs in fish.

Cytochrome c oxidase (COX) subunit 4 has two paralogs in most vertebrates. The mammalian COX4-2 gene is hypoxia responsive, and the protein has a disrupted ATP-binding site that confers kinetic properties on COX that distinguish it from COX4-1. The structure-function of COX4-2 orthologs in other vertebrates remains uncertain. Phylogenetic analyses suggest the two paralogs arose in basal vertebrates, but COX4-2 orthologs diverged faster than COX4-1 orthologs. COX4-1/4-2 protein levels in tilapia tracked mRNA levels across tissues, and did not change in hypoxia, arguing against a role for differential post-translational regulation of paralogs. The heart, and to a lesser extent the brain, showed a size-dependent shift from COX4-1 to COX4-2 (transcript and protein). ATP allosterically inhibited both velocity and affinity for oxygen in COX assayed from both muscle (predominantly COX4-2) and gill (predominantly COX4-1). We saw some evidence of cellular and subcellular discrimination of COX4 paralogs in heart. In cardiac ventricle, some non-cardiomyocyte cells were COX positive but lacked detectible COX4-2. Within heart, the two proteins partitioned to different mitochondrial subpopulations. Cardiac subsarcolemmal mitochondria had mostly COX4-1 and intermyofibrillar mitochondria had mostly COX4-2. Collectively, these data argue that, despite common evolutionary origins, COX4-2 orthologs of fish show unique patterns of subfunctionalization with respect to transcriptional and posttranslation regulation relative to the rodents and primates that have been studied to date.

Accommodative movements of the lens/capsule and the strand that extends between the posterior vitreous zonule insertion zone & the lens equator, in relation to the vitreous face and aging.

PURPOSE: To elucidate the dynamic accommodative movements of the lens capsule, posterior lens and the strand that attaches to the posterior vitreous zonule insertion zone and posterior lens equator (PVZ INS-LE), and their age-related changes. METHODS: Twelve human subjects (ages 19-65 years) and 12 rhesus monkeys (ages 6-27 years) were studied. Accommodation was induced pharmacologically (humans) or by central electrical stimulation (monkeys). Ultrasound biomicroscopy was used to image intraocular structures in both species. Surgical procedures and contrast agents were utilized in the monkey eyes to elucidate function and allow visualization of the intraocular accommodative structures. RESULTS: Human: The posterior pole of the lens moves posteriorly during accommodation in proportion to accommodative amplitude and ciliary muscle movement. Monkey: Similar accommodative movements of the posterior lens pole were seen in the monkey eyes. Following extracapsular lens extraction (ECLE), the central capsule bows backward during accommodation in proportion to accommodative amplitude and ciliary muscle movement, while the peripheral capsule moves forward. During accommodation the ciliary muscle moved forward by ~1.0 mm, pulling forward the vitreous zonule and the PVZ INS-LE structure. During the accommodative response the PVZ INS-LE structure moved forward when the lens was intact and when the lens substance and capsule were removed. In both the monkey and the human eyes these movements declined with age. CONCLUSIONS: The accommodative shape change of the central capsule may be due to the elastic properties of the capsule itself. For these capsule/lens accommodative posterior movements to occur, the vitreous face must either allow for it or facilitate it. The PVZ INS-LE structure may act as a 'strut' to the posterior lens equator (pushing the lens equator forward) and thereby facilitate accommodative forward lens equator movement and lens thickening. The age-related posterior restriction of the ciliary muscle, vitreous zonule and the PVZ-INS LE structure dampens the accommodative lens shape change. Future descriptions of the accommodative mechanism, and approaches to presbyopia therapy, may need to incorporate these findings.

Predicting Ion Sequestration in Charged Polymers with the Steepest-Entropy-Ascent Quantum Thermodynamic Framework.

The steepest-entropy-ascent quantum thermodynamic framework is used to investigate the effectiveness of multi-chain polyethyleneimine-methylenephosphonic acid in sequestering rare-earth ions (Eu3+) from aqueous solutions. The framework applies a thermodynamic equation of motion to a discrete energy eigenstructure to model the binding kinetics of europium ions to reactive sites of the polymer chains. The energy eigenstructure is generated using a non-Markovian Monte Carlo model that estimates energy level degeneracies. The equation of motion is used to determine the occupation probability of each energy level, describing the unique path through thermodynamic state space by which the polymer system sequesters rare-earth ions from solution. A second Monte Carlo simulation is conducted to relate the kinetic path in state space to physical descriptors associated with the polymer, including the radius of gyration, tortuosity, and Eu-neighbor distribution functions. These descriptors are used to visualize the evolution of the polymer during the sequestration process. The fraction of sequestered Eu3+ ions depends upon the total energy of the system, with lower energy resulting in greater sequestration. The kinetics of the overall sequestration are dependent on the steepest-entropy-ascent principle used by the equation of motion to generate a unique kinetic path from an initial non-equilibrium state.

Sex as a risk factor regarding presbyopia in the rhesus monkey.

PURPOSE: To determine the effect of sex as a risk factor regarding presbyopia. METHODS: Maximum accommodation was pharmacologically induced (40% cabachol corneal iontophoresis) in 97 rhesus monkeys (49 males and 48 females) ranging in age from 8 to 36 years old. Accommodation was measured by Hartinger coincidence refractometry. RESULTS: Accommodative amplitude measured refractometrically decreased with age, and the rate of change was not different between males and females (p = 0.827). CONCLUSIONS: Presbyopia is essentially sex neutral, and no one is spared. There may be modest variations between different populations for various reasons, but essentially it is monotonously predictable. At present there is no biological therapeutic.

Predicting Polymer Brush Behavior in Solvents Using the Steepest-Entropy-Ascent Quantum Thermodynamic Framework.

The steepest-entropy-ascent quantum thermodynamic (SEAQT) framework is utilized to study the effects of temperature on polymer brushes. The brushes are represented by a discrete energy spectrum, and energy degeneracies obtained through the replica-exchange Wang-Landau algorithm. The SEAQT equation of motion is applied to the density of states to establish a unique kinetic path from an initial thermodynamic state to a stable equilibrium state. The kinetic path describes the brush's evolution in state space, as it interacts with a thermal reservoir. The predicted occupation probabilities along the kinetic path are used to determine the expected thermodynamic and structural properties. The polymer density profile of a polystyrene brush in cyclohexane solvent is predicted using the equation of motion, and it agrees qualitatively with the experimental density profiles. The Flory-Huggins parameter chosen to describe brush-solvent interactions affects the solvent distribution in the brush but has a minimal impact on the polymer density profile. Three types of nonequilibrium kinetic paths with differing amounts of entropy production are considered: a heating path, a cooling path, and a heating-cooling path. Properties such as tortuosity, radius of gyration, brush density, solvent density, and brush chain conformations are calculated for each path.

Age-related changes in centripetal ciliary body movement relative to centripetal lens movement in monkeys.

The goal was to determine the age-related changes in accommodative movements of the lens and ciliary body in rhesus monkeys. Varying levels of accommodation were stimulated via the Edinger-Westphal (E-W) nucleus in 26 rhesus monkeys, aged 6-27 years, and the refractive changes were measured by coincidence refractometry. Centripetal ciliary process (CP) and lens movements were measured by computerized image analysis of goniovideographic images. Ultrasound biomicroscopy (UBM) at 50 MHz was used to visualize and measure accommodative forward movements of the ciliary body in relation to age, accommodative amplitude, and centripetal CP and lens movements. At approximately 3 diopters of accommodation, the amount of centripetal lens movement required did not significantly change with age (p = 0.10; n = 18 monkeys); however, the amount of centripetal CP movement required significantly increased with age (p = 0.01; n = 18 monkeys), while the amount of forward ciliary body movement significantly decreased with age (p = 0.007; n = 11 monkeys). In the middle-aged animals (12-16.5 years), a greater amount of centripetal CP movement was required to induce a given level of lens movement and thereby a given level of accommodation (p = 0.01), compared to the young animals (6-10 yrs). Collectively, the data suggests that, with age, the accommodative system may be attempting to compensate for the loss of forward ciliary body movement by increasing the amount of centripetal CP movement. This, in turn, would allow enough zonular relaxation to achieve the magnitude of centripetal lens movement necessary for a given amplitude of accommodation.

The zonula, lens, and circumlental space in the normal iridectomized rhesus monkey eye.

PURPOSE: To document zonular orientation and suspension of the lens during accommodation, and age-related changes of the circumlental space (CLS) at rest and during accommodation, in living iridectomized rhesus monkey eyes. METHODS: The CLS was measured in 34 iridectomized eyes of 24 living rhesus monkeys, age 5.7 to 26 years, in the resting and accommodated state, and the orientation of the zonula and suspension of the lens during accommodation was assessed qualitatively. RESULTS: The nonaccommodated CLS decreased significantly with age in both the nasal and temporal quadrants and tended to do so at a slightly faster rate in the temporal quadrant. The CLS correlated significantly with the accommodative amplitude: the greater the CLS the greater the accommodative amplitude. Multiple regression analysis indicated that age and CLS together are better predictors of accommodative amplitude than is age alone. The zonula appeared taut in the nonaccommodated eye throughout the age range despite the age-related decline in CLS. CONCLUSIONS: Characterization of age-related changes in the accommodative apparatus may help to model the system for hypothesis testing. The CLS may be an indicator of presbyopia-related processes in surrounding tissues. However, these results do not prove that the width of the CLS, in and of itself, has a causal relationship with accommodative amplitude, or that changes in the CLS play a pathophysiological role in presbyopia.

Accommodative ciliary body and lens function in rhesus monkeys, I: normal lens, zonule and ciliary process configuration in the iridectomized eye.

PURPOSE: The underlying causes of presbyopia, and the functional relationship between the ciliary muscle and lens during aging are unclear. In the current study, these relationships were studied in rhesus monkeys, whose accommodative apparatus and age-related loss of accommodation are similar to those in humans. METHODS: Centripetal ciliary body and lens equator movements were measured during accommodation in 28 eyes of 21 rhesus monkeys (ages, 5.7-26 years) by goniovideography. Ultrasound biomicroscopy was performed in 21 eyes of 17 monkeys. Narrowing of the angle between the anterior aspect of the ciliary body and the inner aspect of the cornea was used as a surrogate indicator of forward ciliary body movement during accommodation. RESULTS: Average centripetal ciliary body movement in older eyes (age > or =17 years, n = 16) was approximately 20% (0.09 mm) less than in young eyes (age, 6-10 years, n = 6), but not enough to explain the 60% (0.21 mm) loss in centripetal lens movement nor the 76% (10.2 D) loss in accommodative amplitude. Average forward ciliary body movement was 67% (49 degrees ) less in older (n = 11) versus young (n = 6) eyes. Maximum accommodative amplitude correlated significantly with the amplitude of centripetal lens movement (0.02 +/- 0.003 mm/D; n = 28; P < 0.001) and with forward ciliary body movement (3.34 +/- 0.54 deg/D; n = 21; P = 0.01). CONCLUSIONS: Decreased lens movement with age could be in part secondary to extralenticular age-related changes, such as loss of ciliary body forward movement. Ciliary body centripetal movement may not be the limiting component in accommodation in the older eye.

Application of canaloplasty in glaucoma gene therapy: where are we?

PURPOSE: Schlemm's canal (SC) inner wall is adjacent to the juxtacanalicular trabecular meshwork (TM) over their entire circumference. We seek to transfer reporter and therapeutic genes to these outflow-modulating tissues via canaloplasty surgery in live monkeys. METHODS: A standard canaloplasty surgical approach was performed in cynomolgus monkeys using flexible canaloplasty catheters, modified for monkey eyes with a 175-µm outer diameter and an LED-lighted tip. A 6-0 prolene suture was used for the exact localization of SC. Trypan blue was injected during catheter withdrawal to document catheter placement within SC and to determine ease of injecting fluid into SC. Before, during, and after the injection, the position of the catheter and the anatomic details were video-captured with an externally positioned noncontact endoscopic imaging system and 50 mHz ultrasound biomicroscopy (UBM). RESULTS: A 360° catheterization and injection of dye into SC was achieved. Suture, catheter, and trypan blue were imaged with the endoscope camera system and the catheter was also visualized with UBM. Trypan blue was seen in the SC over 5 clock hours after a 1 clock-hour insertion of the catheter. CONCLUSIONS: A modified canaloplasty catheter device might be used for gene delivery to the SC/TM area without circumferential catheterization. Further studies comparing different delivery methods of the vector/transgene into the SC using canaloplasty are needed.

Extralenticular and lenticular aspects of accommodation and presbyopia in human versus monkey eyes.

PURPOSE: To determine if the accommodative forward movements of the vitreous zonule and lens equator occur in the human eye, as they do in the rhesus monkey eye; to investigate the connection between the vitreous zonule posterior insertion zone and the posterior lens equator; and to determine which components-muscle apex width, lens thickness, lens equator position, vitreous zonule, circumlental space, and/or other intraocular dimensions, including those stated in the objectives above-are most important in predicting accommodative amplitude and presbyopia. METHODS: Accommodation was induced pharmacologically in 12 visually normal human subjects (ages 19-65 years) and by midbrain electrical stimulation in 11 rhesus monkeys (ages 6-27 years). Ultrasound biomicroscopy imaged the entire ciliary body, anterior and posterior lens surfaces, and the zonule. Relevant distances were measured in the resting and accommodated eyes. Stepwise regression analysis determined which variables were the most important predictors. RESULTS: The human vitreous zonule and lens equator move forward (anteriorly) during accommodation, and their movements decline with age, as in the monkey. Over all ages studied, age could explain accommodative amplitude, but not as well as accommodative lens thickening and resting muscle apex thickness did together. Accommodative change in distances between the vitreous zonule insertion zone and the posterior lens equator or muscle apex were important for predicting accommodative lens thickening. CONCLUSIONS: Our findings quantify the movements of the zonule and ciliary muscle during accommodation, and identify their age-related changes that could impact the optical change that occurs during accommodation and IOL function.

Accommodative movements of the vitreous membrane, choroid, and sclera in young and presbyopic human and nonhuman primate eyes.

PURPOSE: We report, for the first time to our knowledge, dynamic movements of the vitreous membrane and peripheral choroid during accommodation, and age-related changes in the anterior sclera. METHODS: We studied 11 rhesus monkeys (ages 6-27 years) and 12 human subjects (ages 19-65 years). Accommodation was induced pharmacologically in human subjects and by central electrical stimulation in the monkeys. Ultrasound biomicroscopy, endoscopy, and contrast agents were used to image various intraocular structures. RESULTS: In the monkey, the anterior hyaloid membrane bows backward during accommodation in proportion to accommodative amplitude and lens thickening. A cleft exists between the pars plicata region and the anterior hyaloid membrane, and the cleft width increases during accommodation from 0.79 ± 0.01 mm to 1.01 ± 0.02 mm in young eyes (n = 2, P < 0.005), as fluid from the anterior chamber flows around the lens equator toward the cleft. In the older eyes the cleft width was 0.30 ± 0.19 mm, which during accommodation increased to 0.45 ± 0.20 mm (n = 2). During accommodation the ciliary muscle moved forward by approximately 1.0 mm, pulling forward the choroid, retina, vitreous zonule, and the neighboring vitreous interconnected with the vitreous zonule. Among the humans, in the older eyes the scleral contour bowed inward in the region of the limbus, compared to the young eyes. CONCLUSIONS: The monkey anterior hyaloid bends posteriorly during accommodation in proportion to accommodative amplitude and the sclera bows inward with increasing age in both species. Future descriptions of the accommodative mechanism, and approaches to presbyopia therapy, may need to incorporate these findings.

Ultrashort-pulse lasers treating the crystalline lens: will they cause vision-threatening cataract? (An American Ophthalmological Society thesis).

PURPOSE: To demonstrate that ultrashort-pulse laser treatment in the crystalline lens does not form a focal, progressive, or vision-threatening cataract. METHODS: An Nd:vanadate picosecond laser (10 ps) with prototype delivery system was used. Primates: 11 rhesus monkey eyes were prospectively treated at the University of Wisconsin (energy 25-45 µJ/pulse and 2.0-11.3M pulses per lens). Analysis of lens clarity and fundus imaging was assessed postoperatively for up to 4½ years (5 eyes). Humans: 80 presbyopic patients were prospectively treated in one eye at the Asian Eye Institute in the Philippines (energy 10 µJ/pulse and 0.45-1.45M pulses per lens). Analysis of lens clarity, best-corrected visual acuity, and subjective symptoms was performed at 1 month, prior to elective lens extraction. RESULTS: Bubbles were immediately seen, with resolution within the first 24 to 48 hours. Afterwards, the laser pattern could be seen with faint, noncoalescing, pinpoint micro-opacities in both primate and human eyes. In primates, long-term follow-up at 4½ years showed no focal or progressive cataract, except in 2 eyes with preexisting cataract. In humans, <25% of patients with central sparing (0.75 and 1.0 mm radius) lost 2 or more lines of best spectacle-corrected visual acuity at 1 month, and >70% reported acceptable or better distance vision and no or mild symptoms. Meanwhile, >70% without sparing (0 and 0.5 mm radius) lost 2 or more lines, and most reported poor or severe vision and symptoms. CONCLUSIONS: Focal, progressive, and vision-threatening cataracts can be avoided by lowering the laser energy, avoiding prior cataract, and sparing the center of the lens.

Lens diameter and thickness as a function of age and pharmacologically stimulated accommodation in rhesus monkeys.

Uncertainty exists regarding accommodative and age changes in lens diameter and thickness in humans and monkeys. In this study, unaccommodated and accommodated refraction, lens diameter, and lens thickness were measured in rhesus monkeys across a range of ages. Iridectomized eyes were studied in 33 anesthetized monkeys aged 4-23 years. Refraction was measured using a Hartinger coincidence refractometer and lens thickness was measured with A-scan ultrasound. Lens diameters were measured with image analysis from slit-lamp images captured via a video camera while a saline filled, plano perfusion lens was placed on the cornea. Accommodation was pharmacologically stimulated with 2% pilocarpine via the perfusion lens in 21 of the monkeys and lens diameters were measured until a stable minimum was achieved. Refraction and lens thickness were measured again after the eye was accommodated. Unaccommodated lens thickness increased linearly with age by 0.029 mm/year while unaccommodated lens diameter showed no systematic change with age. Accommodative amplitude decreased by 0.462 D/year in response to pilocarpine. The accommodative increase in lens thickness decreased with age by 0.022 mm/year. The accommodative decrease in lens diameter declined linearly with age by 0.021 mm/year. Rhesus monkeys undergo the expected presbyopic changes including increasing lens thickness and a decreasing ability of the lens to undergo changes in thickness and diameter with accommodation, however without an age-related change in unaccommodated lens diameter. As in humans, the age-related decrease in accommodative amplitude in rhesus monkeys cannot be attributed to an age-related increase in lens diameter.

Surgical intervention and accommodative responses, II: forward ciliary body accommodative movement is facilitated by zonular attachments to the lens capsule.

PURPOSE: To determine the role of the lens and the lens capsule in the three-dimensional architecture of the ciliary muscle at rest and during accommodation, in live rhesus monkeys and in histologic sections, by removing the entire lens, or only the lens nucleus and cortex, while leaving the posterior capsule in place. METHODS: In 15 rhesus monkey eyes, aged 6 to 27 years, accommodation was induced by central stimulation of the Edinger-Westphal nucleus before and after intra- or extracapsular lens extraction (ICLE, ECLE). Forward ciliary body movement and ciliary body width were measured by ultrasound biomicroscopy (UBM, 50 MHz). The monkeys were then killed, the eyes were examined morphologically in 1-microm sections, and the shape of the ciliary muscle was compared with that obtained from UBM images. RESULTS: The shape of the ciliary muscle in eyes undergoing ECLE (n = 5) did not differ from that in control eyes. In contrast, after ICLE (n = 10), accommodative forward ciliary body movement (P < 0.01) and thickness were decreased (P < 0.001), length was increased (P = 0.058), and the inner apex was located more posteriorly than in control eyes (P < 0.005). Histologic and in vivo data were similar and showed that the ciliary muscle maintained its triangular shape only if the lens capsule (with or without the lens substance) was present. CONCLUSIONS: The posterior lens capsule and anterior zonular attachments facilitate forward accommodative ciliary body movement. Lens substance extraction procedures that leave the posterior capsule intact, similar to those used clinically, do not affect the capsule/zonular/muscular system movements, an important finding for accommodating intraocular lens development.

Surgical intervention and accommodative responses, I: centripetal ciliary body, capsule, and lens movements in rhesus monkeys of various ages.

PURPOSE: To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. METHODS: In 18 rhesus monkey eyes (aged 6-27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extracapsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis (ARZ). Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. RESULTS: Centripetal accommodative CP and capsule movement increased in velocity and amplitude after, compared with before, ECLE regardless of age (n = 5). The presence of the lens substance retarded capsule movement by approximately 21% in the young eyes and by approximately 62% in the older eyes. Post-ICLE compared with pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disrupted (n = 7), but not in eyes in which the anterior vitreous was left intact (n = 2). After anterior regional zonulolysis (n = 4), lens position shifted toward the lysed quadrant during accommodation. CONCLUSIONS: The presence of the lens substance, capsule zonular attachments, and Wieger's ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce approximately 6 D of accommodation in the presence of a normal, young crystalline lens or a similar surrogate.