Lens Elasticity Research Articles

Effect of compound treatments on mouse lens viscoelasticity

Previous studies have shown that pharmaceutical agents such as lipoic acid have the ability to soften the lens, presenting a promising avenue for treating presbyopia. One obstacle encountered in the preclinical stage of such agents is the need for precise measurements of lens elasticity in experimental models. This study aimed to evaluate the effects of 25-hydroxycholesterol, lipoic acid, and obeticholic acid on the viscoelastic properties of mouse lenses using a custom-built elastometer system. Data were acquired on lenses from C57BL/6J female mice from two age groups: young (age: 8–10 weeks) and old (age: 32–43 weeks). OD lenses were used as the control and OS lenses were treated. Control lenses were immersed in Dulbecco's Modified Eagle Medium (DMEM) and treatment lenses were immersed in a compound solution containing 25-hydroxycholesterol (5 young and 5 old), lipoic acid at 2.35 mM (5 young and 5 old), lipoic acid at 0.66 mM (5 old), or obeticholic acid (5 old) at 37 °C for 18 h. After treatment, the mouse lenses were placed in a DMEM-filled chamber within a custom-built elastometer system that recorded the load and lens shape as the lens was compressed by 600 μm at a speed of 50 μm/s. The load was continuously recorded during compression and during stress-relaxation. The compression phase was fit with a linear function to quantify lens stiffness. The stress-relaxation phase was fit with a 3-term exponential relaxation model providing relaxation time constants (t1, t2, t3), and equilibrium load. The lens stiffness, time constants and equilibrium load were compared for the control and treated groups. Results revealed an increase in stiffness with age for the control group (young: 1.16 ± 0.11 g/mm, old: 1.29 ± 0.14 g/mm) and relaxation time constants decreased with age (young: t1 = 221.9 ± 29.0 s, t2 = 24.7 ± 3.8 s, t3 = 3.12 ± 0.87 s, old: t1 = 183.0 ± 22.0 s, t2 = 20.6 ± 2.6 s and t3 = 2.24 ± 0.43 s). Among the compounds tested, only 25-hydroxycholesterol produced statistically significant changes in the lens stiffness, relaxation time constants, and equilibrium load. In conclusion, older mouse lenses are stiffer and less viscous than young mouse lenses. Notably, no significant change in lens stiffness was observed following treatment with lipoic acid, contrary to previous findings.

Characterization of the viscoelastic properties of in vitro crystalline lens samples using ultrasound elastography

With aging, the stiffening of the crystalline lens [K. R. Heys et al., Mol. Vision 10, 956 (2004); R. F. Fisher, J. Physiol. 212(1), 147–180 (1971)] can hinder accommodation and reduce near-vision in more than 75% of individuals above 40 year old [T. R. Fricke et al., Ophthalmology 125(10), 1492–1499 (2018)], an impairment known as presbyopia. Mapping lens elasticity using shear wave elastography holds significant promise for monitoring potential treatments for presbyopia. However, because of the transparency of the lens to ultrasound, the tracking of waves can be performed only on its boundaries. The goal of this study is to characterize the viscoelastic properties of in vitro crystalline lens samples with a curvilinear harmonic method based on noise correlation algorithms. This procedure consists of precise measurements of the dispersion of surface waves across a large frequency range (0.1–3.5 kHz), thus allowing for clear identification of the wave properties needed to correctly estimate the elasticity. The proposed method was applied to gelatin phantoms and excised porcine lens samples. This enabled the observation of two regions in the dispersion curves: a sharp decrease in dispersion at low frequencies (<1 kHz), which was partly due to guided waves, and a smoother slope at high frequencies (>1 kHz), which was attributed to viscoelastic dispersion. In contrast to previous studies, shear elasticity and viscosity moduli were computed at higher frequencies with a Kelvin–Voigt model. If our approach confirms the shear viscosity of lenses, then the shear elastic moduli of lenses are almost an order of magnitude greater than the results of previous studies.

Shear wave elastography (SWE) for the measurement of lens elasticity in the context of monitoring a presbyopia treatment by ultrasonic cavitation

Presbyopia is a progressive loss of accommodation capacity due to a rigidification of the lens. In order to prove the efficiency of ultrasonic cavitation to soften the lens, curvilinear SWE has been developed. It is a method to measure stiffness based on the tracking of surface waves on the outer layer of lens. Experimental models have been implemented: flat phantoms and beads made of 10% and 15% of porcine gelatin and finally porcine lenses (young: 6 months and old: 1 to 6 years). A mechanical vibrator created vibrations (0.1–3.5kHz) and an ultrafast ultrasound imaging system was used to track the propagating waves. From the curvature of the frequency domain of the cross-correlated displacement field, the wavelength and velocity were computed. Experimental models enable to validated the method with dispersion curves substantially different between both concentrations. Results in lenses are similar: a dispersion curve highly dependent of the frequency, reflecting the complexity of elastic wave propagating in a multilayered medium surrounded by a membrane. To retrieve quantitative elasticity data, advanced numerical models have to be developed. This method will be applied on lenses treated by cavitation to assess its potential for treating presbyopia.

Promotion of Protein Solubility and Reduction in Stiffness in Human Lenses by Aggrelyte-1: Implications for Reversing Presbyopia.

With aging, human lenses lose the ability to focus on nearby objects due to decreases in accommodative ability, a condition known as presbyopia. An increase in stiffness or decrease in lens elasticity due to protein aggregation and insolubilization are the primary reasons for presbyopia. In this study, we tested aggrelyte-1 (S,N-diacetyl glutathione diethyl ester) for its ability to promote protein solubility and decrease the stiffness of lenses through its dual property of lysine acetylation and disulfide reduction. Treatment of water-insoluble proteins from aged human lenses (58-75 years) with aggrelyte-1 significantly increased the solubility of those proteins. A control compound that did not contain the S-acetyl group (aggrelyte-1C) was substantially less efficient in solubilizing water-insoluble proteins. Aggrelyte-1-treated solubilized protein had significant amounts of acetyllysine, as measured by Western blotting and LC-MS/MS. Aggrelytes increased the protein-free thiol content in the solubilized protein. Aged mouse (7 months) and human (44-66 years) lenses treated with aggrelyte-1 showed reduced stiffness accompanied by higher free thiol and acetyllysine levels compared with those treated with aggrelyte-1C or untreated controls. Our results suggested that aggrelyte-1 reduced lens stiffness through acetylation followed by disulfide reduction. This proof-of-concept study paves the way for developing aggrelyte-1 and related compounds to reverse presbyopia.

In situ assessment of lens elasticity with noncontact optical coherence elastography.

Lens biomechanics has great potential for application in clinical diagnostics and treatment monitoring of presbyopia and cataracts. However, current approaches to lens elastography do not meet the desired safety or sensitivity for clinical application. In this regard, we propose a noncontact optical coherence elastography (OCE) method to facilitate quantitative in situ imaging of lens elasticity. Elastic waves induced by air-pulse stimulation on the limbus propagate to the lens and are then imaged using custom-built swept-source optical coherence tomography to obtain the elastic wave velocity and Young's modulus. The proposed OCE method was first validated by comparing the results of in situ and in vitro measurements of porcine lenses. The results demonstrate that the Young's modulus measured in situ was highly consistent with that measured in vitro and had an intraclass correlation coefficient of 0.988. We further investigated the elastic changes induced by cold storage and microwave heating. During 36-hour cold storage, the mean Young's modulus gradually increased (from 5.62 ± 1.24 kPa to 11.40 ± 2.68 kPa, P < 0.0001, n = 9) along with the formation of nuclear opacities. 15-second microwave heating caused a greater increase in the mean Young's modulus (from 6.86 ± 1.21 kPa to 25.96 ± 8.64 kPa, P < 0.0025, n = 6) without apparent cataract formation. Accordingly, this study reports the first air-pulse OCE measurements of in situ lenses, which quantified the loss of lens elasticity during simulated cataract development with good repeatability and sensitivity, thus enhancing the potential for adoption of lens biomechanics in the clinic.

Membrane elasticity modulated by cholesterol in model of porcine eye lens-lipid membrane

Experimental evidence shows that the eye lens loses its elasticity dramatically with age. It has also been reported that the cholesterol (Chol) content in the eye lens fiber cell plasma membrane increases significantly with age. High Chol content leads to the formation of cholesterol bilayer domains (CBDs) in the lens membrane. The role of high Chol associated with lens elasticity is unclear. The purpose of this research is to investigate the membrane elasticity of the model of porcine lens-lipid (MPLL) membrane with increasing Chol content to elucidate the role of high Chol in lens membrane elasticity. In this study, we used atomic force microscopy (AFM) to study the mechanical properties (breakthrough force and area compressibility modulus (KA)) of the MPLL membrane with increasing Chol content where KA is the measure of membrane elasticity. We varied Chol concentration in Chol/MPLL membrane from 0 to ∼71 mol%. Supported Chol/MPLL membranes were prepared by fusion of small unilamellar vesicles (SUVs) on top of a flat mica surface. SUVs of the Chol/MPLL lipid mixture were prepared with the rapid solvent exchange method followed by probe-tip sonication. For the Chol/MPLL mixing ratio of 0, AFM image showed the formation of two distinct phases of the membrane, i.e., liquid-disordered phase (ld) and solid-ordered phase (so) membrane. However, with Chol/MPLL mixing ratio of 0.5 and above, only liquid-ordered phase (lo) membrane was formed. Also, two distinct breakthrough forces corresponding to ld and so were observed for Chol/MPLL mixing ratio of 0, whereas only one breakthrough force was observed for membranes with Chol/MPLL mixing ratio of 0.5 and above. No significant difference in the membrane surface roughness was measured with increasing Chol content for these membranes; however, breakthrough force and KA for lo membrane increased when Chol/MPLL mixing ratio was increased from 0.5 to 1. Interestingly above the Chol/MPLL mixing ratio of 1, both breakthrough force and KA decreased, indicating the formation of CBDs. Furthermore, these results showed that membrane elasticity increases at high Chol content, suggesting that high Chol content in lens membrane might be responsible for maintaining lens membrane elasticity.

An AFM Approach Applied in a Study of α-Crystallin Membrane Association: New Insights into Lens Hardening and Presbyopia Development.

The lens of the eye loses elasticity with age, while α-crystallin association with the lens membrane increases with age. It is unclear whether there is any correlation between α-crystallin association with the lens membrane and loss in lens elasticity. This research investigated α-crystallin membrane association using atomic force microscopy (AFM) for the first time to study topographical images and mechanical properties (breakthrough force and membrane area compressibility modulus (KA), as measures of elasticity) of the membrane. α-Crystallin extracted from the bovine lens cortex was incubated with a supported lipid membrane (SLM) prepared on a flat mica surface. The AFM images showed the time-dependent interaction of α-crystallin with the SLM. Force spectroscopy revealed the presence of breakthrough events in the force curves obtained in the membrane regions where no α-crystallin was associated, which suggests that the membrane’s elasticity was maintained. The force curves in the α-crystallin submerged region and the close vicinity of the α-crystallin associated region in the membrane showed no breakthrough event within the defined peak force threshold, indicating loss of membrane elasticity. Our results showed that the association of α-crystallin with the membrane deteriorates membrane elasticity, providing new insights into understanding the molecular basis of lens hardening and presbyopia.

Alpha-crystallin-membrane interactions using atomic force microscopy

Several studies suggest that the lens loses its elasticity with age. It has also been reported that α-crystallin binding to the lens membrane increases with age. It is unclear whether there is any correlation between α-crystallin binding to lens membrane and loss in lens elasticity with age. The purpose of this research is to investigate the membrane elasticity with α-crystallin binding. We have used atomic force microscopy (AFM) to study the mechanical properties (breakthrough force and membrane's area compressibility modulus (KA)) of the membrane with α-crystallin binding, where KA is the measure of membrane elasticity.

Comparison of methods to experimentally induce opacification and elasticity change in ex vivo porcine lenses

At the moment, cataract, which is the opacification of the eye’s lens, can only be treated by surgery. In order to develop and test new pharmacological treatment strategies for the disease, there is a need for an appropriate in vitro model using ex vivo animal lenses. In this study, porcine lenses were incubated in either culture medium, glucose, triamcinolone acetonide, sodium chloride, hydrogen peroxide, sodium selenite, neutral buffered formalin, or were exposed to microwave heating to experimentally induce lens opacification. Changes in the lens morphology, weight, size, and elasticity were monitored 7 days after treatment. The fastest induction of dense opacification was seen in lenses exposed to sodium chloride, neutral buffered formalin, and microwave heating. No change in the size and weight of the lenses were detected, whereas loss in elasticity could be detected in lenses treated with formalin solution or microwave heating. Thus, neutral buffered formalin- and microwave-treated ex vivo porcine lenses seem to be a suitable model for mature cataracts, whereas hypertonic sodium chloride may be useful for studies on osmolarity-induced lens opacification.

Measuring the effects of postmortem time and age on mouse lens elasticity using atomic force microscopy

The mouse lens is frequently used both in vivo and ex vivo in ophthalmic research to model conditions affecting the human lens, such as presbyopia. The mouse lens has a delicate structure which is prone to damage and biomechanical changes both before and after extraction from the whole globe. When not properly controlled for, these changes can confound the biomechanical analysis of mouse lenses. In this study, atomic force microscopy microindentation was used to assess changes in the Young's Modulus of Elasticity of the mouse lens as a function of mouse age and postmortem time. Old mouse lenses measured immediately postmortem were significantly stiffer than young mouse lenses (p = 0.028). However, after 18 h of incubation, there was no measurable difference in lens stiffness between old and young mouse lenses (p = 0.997). This demonstrates the need for careful experimental control in experiments using the mouse lens, especially regarding postmortem time.

Effect of Alpha-Glucosyl-Hesperidin Consumption on Lens Sclerosis and Presbyopia.

Presbyopia is characterized by a decline in the ability to accommodate the lens. The most commonly accepted theory for the onset of presbyopia is an age-related increase in the stiffness of the lens. However, the cause of lens sclerosis remains unclear. With age, water microcirculation in the lens could change because of an increase in intracellular pressure. In the lens, the intracellular pressure is controlled by the Transient Receptor Potential Vanilloid (TRPV) 1 and TRPV4 feedback pathways. In this study, we tried to elucidate that administration of α-glucosyl-hesperidin (G-Hsd), previously reported to prevent nuclear cataract formation, affects lens elasticity and the distribution of TRPV channels and Aquaporin (AQP) channels to meet the requirement of intracellular pressure. As a result, the mouse control lens was significantly toughened compared to both the 1% and 2% G-Hsd mouse lens treatments. The anti-oxidant levels in the lens and plasma decreased with age; however, this decrease could be nullified with either 1% or 2% G-Hsd treatment in a concentration- and exposure time-dependent manner. Moreover, G-Hsd treatment affected the TRPV4 distribution, but not TRPV1, AQP0, and AQP5, in the peripheral area and could maintain intracellular pressure. These findings suggest that G-Hsd has great potential as a compound to prevent presbyopia and/or cataract formation.

Oral administration of resveratrol or lactic acid bacterium improves lens elasticity

A decrease in the elasticity of the ocular lens during aging is associated with loss of the accommodative ability of the eye, leading to presbyopia. Although near vision impairment is a social issue affecting the length of healthy life expectancy and productivity of elderly people, an effective treatment to improve near vision has not yet become available. Here we examined the effect of Enterococcus faecium WB2000, Lactobacillus pentosus TJ515, and resveratrol on lens elasticity in rats, where the stiffness of the ocular lens increases exponentially during the aging process. A combination of WB2000 and resveratrol improved lens elasticity not only in the long term but also with just short-term treatment. In addition, TJ515 decreased stiffness in the eye lens with long-term treatment. Therefore, the oral administration of WB2000 and resveratrol or TJ515 may be a potential approach for managing the progression of near vision impairment.

Age-Related Lens Elasticity Changes and Homeostatic Abnormalities

Age-Related Lens Elasticity Changes and Homeostatic Abnormalities

Oral consumption of α-glucosyl-hesperidin could prevent lens hardening, which causes presbyopia

Presbyopia is one of the most well-known diseases of the eye, predominantly affecting the adult population after 50 years’. Due to hardening of the lens and failure of accommodative change, patients lose the ability to focus on near objects. This eye symptom is reported to be an early symptom of age-related nuclear cataract, and we have previously reported that hesperetin treatment could delay the onset of nuclear cataractogenesis induced by sodium selenite. In this study, we examined whether oral intake of α-glucosyl-hesperidin (G-Hsd), which has greater water solubility than hesperetin, could delay the onset of presbyopia. G-Hsd treatment protected lens elasticity, upregulated the mRNA expression of anti-oxidative enzymes like glutathione reductase and thioredoxin reductase 1 in the plasma and lens, and prevented premature cataract symptoms in selenite-induced cataract rat lens. Thus, the anti-presbyopic effects of G-Hsd were attributed, at least in part, to its antioxidant effects. G-Hsd represents the first oral treatment agent with anti-presbyopia and/or anti-cataract properties.

Difference in Pupillary Diameter as an Important Factor for Evaluating Amplitude of Accommodation: A Prospective Observational Study.

Presbyopia is increasing globally due to aging and the widespread use of visual display terminals. Presbyopia is a decrease in the eye’s amplitude of accommodation (AA) due to loss of crystalline lens elasticity. AA differs widely among individuals. We aimed to determine the factors that cause presbyopia, other than advanced age, for early medical intervention. We examined 95 eyes of 95 healthy volunteers (33 men, 62 women) aged 22–62 years (mean: 37.22 ± 9.77 years) with a corrected visual acuity of ≥1.0 and without other eye afflictions except ametropia. Subjective refraction, AA, maximum and minimum pupillary diameters during accommodation, axial length of the eye, and crystalline lens thickness were measured. AA was measured using an auto refractometer/keratometer/tonometer/pachymeter. The difference between maximum and minimum pupillary diameters was calculated. On multiple regression analysis, age and difference in pupillary diameter were both significantly and independently associated with AA in participants aged <44 years, but not in those aged ≥45 years. Our results suggest that the difference in pupillary diameter could be an important age-independent factor for evaluating AA in healthy individuals without cataract. Thus, improving the difference in pupillary diameter values could be an early treatment target for presbyopia.

Effects of Hyperoxia on the Refraction in Murine Neonatal and Adult Models.

Whether hyperoxia affects the refraction in neonatal and adult mice is unknown. The mice exposed to 85% oxygen at postnatal 8 days (P8d) for 3 days and the mice exposed to normal air were assigned to the neonatal hyperoxia and normoxia groups, respectively. The refraction, the corneal curvature radius (CR) and the axial length (AL) were measured at P30d and P47d. Postnatal 6 weeks (P6w) adult mice were divided into the adult hyperoxia and normoxia groups. These parameters were measured before oxygen exposure, after 1 and 6 weeks, and every 7 weeks. The lens elasticity was measured at P7w and P26w by enucleation. The neonatal hyperoxia group showed a significantly larger myopic change than the neonatal normoxia group (P47d −6.56 ± 5.89 D, +4.11 ± 2.02 D, p < 0.001), whereas the changes in AL were not significantly different (P47d, 3.31 ± 0.04 mm, 3.31 ± 0.05 mm, p = 0.852). The adult hyperoxia group also showed a significantly larger myopic change (P12w, −7.20 ± 4.09 D, +7.52 ± 2.54 D, p < 0.001). The AL did not show significant difference (P12w, 3.44 ± 0.03 mm, 3.43 ± 0.01 mm, p = 0.545); however, the CR in the adult hyperoxia group was significantly smaller than the adult normoxia group (P12w, 1.44 ± 0.03 mm, 1.50 ± 0.03 mm, p = 0.003). In conclusion, hyperoxia was demonstrated to induce myopic shift both in neonatal and adult mice, which was attributed to the change in the CR rather than the AL. Elucidation of the mechanisms of hyperoxia and the application of this result to humans should be carried out in future studies.

Pathophysiology of cataracts

Cataracts result in significant vision reduction. It is estimated that cataract was responsible for the morbidity of 10.8 million people (of overall 32.4 million blind people around the world), and 35.1 million people (of overall 191 million vision impaired people around the world). It is also the most common cause of blindness in many countries, including Saudi Arabia. We tried to understand, in details, the pathogenesis of cataracts, with special focus on how ageing is a contributory factor in its development. We conducted this review using a comprehensive search of MEDLINE, PubMed and EMBASE from January 1970 to March 2017. The following search terms were used: cataracts, pathogenesis of cataracts, pathophysiology in cataracts, ageing lens, aging and vision loss, lens degeneration. Cataracts heavily impacts the vision, thereby, the lives of individuals suffering from it. Due to its large prevalence, the impact on economy is large too. Although surgery is very promising, newer approach is focusing on its pathophysiology to emphasize on preventive options. Several changes, including oxidative stress, reduction in reductive enzymes, lens elasticity, and specific age related degeneration play major roles in its pathophysiology.

Suppression of presbyopia progression with pirenoxine eye drops: experiments on rats and non-blinded, randomized clinical trial of efficacy

Various methods can correct presbyopia, but all require devices or surgeries. Recently, supplements or warming devices to relieve presbyopic symptoms have been developed, but no eye drops have been developed. We screened certain compounds possibly related to lens degeneration and identified pirenoxine, which has been used for cataracts, as a possible new pharmacologic treatment for presbyopia. We first researched the anti-presbyopic activity of pirenoxine in rats. The lens elasticity significantly (p = 0.028) increased with exposure to tobacco smoke for 12 days, and pirenoxine eye drops significantly (p < 0.001) suppressed lens hardening, which causes presbyopia in humans. In a parallel randomized controlled clinical study of the subjects in their fifth decade of life, the objective accommodative amplitude (AA) decreased significantly (p < 0.01) by 0.16 diopter (D) in the control group, and there was no detectable change in the treatment group after a 6-month treatment period, suggesting that pirenoxine eye drops might prevent progression of presbyopia. Subjects in their sixth decade of life, in whom the AA was already nearly 0 D, did not show similar results. Pirenoxine eye drops might be a new and the first pharmacologic treatment for preventing progression of presbyopia.

Changes in Ocular Parameters and Intraocular Lens Powers in Aging Cycloplegic Eyes

Age-related changes in lens elasticity and ciliary muscle contractility can affect how ocular parameters respond to cycloplegia, and therefore intraocular lens (IOL) power measurements calculated by formulas using anterior chamber depth (ACD), lens thickness (LT), or white-to-white (WtW) for effective lens position prediction can vary. In response, using swept-source optical biometry in prepresbyopic and presbyopic eyes, we investigated changes in ocular parameters and IOL power calculations attributable to cycloplegia. Cross-sectional study. In 38 prepresbyopic and 42 presbyopic eyes, we measured pupil diameter, radius of corneal curvature values, central corneal thickness, WtW, ACD, LT, and axial length both before and after cycloplegia. We determined IOL power calculations with the Sanders-Retzlaff-Kraff/theoretical, Holladay 2, and Haigis formulas. To pinpoint the effect of cycloplegia, we recorded refractive predictions in pre- and postdilation conditions according to the same IOL power calculations, even if postdilation IOL power calculations had changed. With cycloplegia, pupil diameter changed significantly more in presbyopic eyes (P < .001). Central corneal thickness decreased in prepresbyopic eyes (P= .048), whereas WtW increased in presbyopic eyes (P= .02). In both groups, ACD and LT changed significantly (P < .001). IOL power calculations according to the Holladay 2 formula differed in prepresbyopic eyes (P= .042), and refractive predictions with the Holladay 2 and Haigis formulas differed significantly in prepresbyopic eyes (P= .043 and P= .022, respectively). Surgeons should consider the effect of cycloplegia on refractive prediction errors and IOL power calculations determined with Haigis and Holladay 2 formulas, especially in prepresbyopic ages.

Protein Disulfide Levels and Lens Elasticity Modulation: Applications for Presbyopia.

PurposeThe purpose of the experiments described here was to determine the effects of lipoic acid (LA)-dependent disulfide reduction on mouse lens elasticity, to synthesize the choline ester of LA (LACE), and to characterize the effects of topical ocular doses of LACE on mouse lens elasticity.MethodsEight-month-old mouse lenses (C57BL/6J) were incubated for 12 hours in medium supplemented with selected levels (0–500 μM) of LA. Lens elasticity was measured using the coverslip method. After the elasticity measurements, P-SH and PSSP levels were determined in homogenates by differential alkylation before and after alkylation. Choline ester of LA was synthesized and characterized by mass spectrometry and HPLC. Eight-month-old C57BL/6J mice were treated with 2.5 μL of a formulation of 5% LACE three times per day at 8-hour intervals in the right eye (OD) for 5 weeks. After the final treatment, lenses were removed and placed in a cuvette containing buffer. Elasticity was determined with a computer-controlled instrument that provided Z-stage upward movements in 1-μm increments with concomitant force measurements with a Harvard Apparatus F10 isometric force transducer. The elasticity of lenses from 8-week-old C57BL/6J mice was determined for comparison.ResultsLipoic acid treatment led to a concentration-dependent decrease in lens protein disulfides concurrent with an increase in lens elasticity. The structure and purity of newly synthesized LACE was confirmed. Aqueous humor concentrations of LA were higher in eyes of mice following topical ocular treatment with LACE than in mice following topical ocular treatment with LA. The lenses of the treated eyes of the old mice were more elastic than the lenses of untreated eyes (i.e., the relative force required for similar Z displacements was higher in the lenses of untreated eyes). In most instances, the lenses of the treated eyes were even more elastic than the lenses of the 8-week-old mice.ConclusionsAs the elasticity of the human lens decreases with age, humans lose the ability to accommodate. The results, briefly described in this abstract, suggest a topical ocular treatment to increase lens elasticity through reduction of disulfides to restore accommodative amplitude.