Cataractous Lenses Research Articles

CELF1 Selectively Regulates Alternative Splicing of DNA Repair Genes Associated With Cataract in Human Lens Cell Line.

Cataract is a global eye disease caused by the opacification of lens, while its underlying molecular pathogenesis is not clear, making it difficult for prevention. CELF1, an RNA binding protein, mediates Alternative Splicing (AS) of genes involved in diverse diseases and regulates development or defects of lens. Utilizing transcriptome-wide approaches, we analyzed and compared AS patterns between human lens epithelial cells (SRA01/04) with CELF1 overexpression (CELF1-OE) and control cells. Extensive changes in AS patterns upon CELF1-OE were identified in SRA01/04 cells. We finally identified 840 CELF1-regulated AS events (RASEs) and found that CELF1-OE preferred to repress exon skipping events in SRA01/04 cells. CELF1-regulated AS genes were enriched in the regulation of DNA repair, cellular response to DNA damage stimulus, and apoptosis pathways (including HMGA2, CSNK1E, and YAP1). These biological functions and pathways have been reported to be associated with lens development or other eye diseases. To further explore the mechanisms of CELF1 in regulating AS genes, we downloaded and re-analyzed a set of CELF1-RNA interactome data. We found that 194 genes were bound and regulated by CELF1 at the AS level. 10 genes involved in DNA repair-related pathways were also bound by CELF1. Motif analysis for CELF1-bound peaks and splicing sites of RASEs showed that CELF1 regulates AS by binding to the AGGU[AG]AG motif in SRA01/04 cells. CELF1 could mediate AS of DNA repair-related genes through directly binding to their transcripts with distinct motif bias. The functional mechanism of CELF1 may ultimately participate in cataract formation and lens development.

Impact of α-crystallin protein loss on zebrafish lens development

The α-crystallin small heat shock proteins contribute to the transparency and refractive properties of the vertebrate eye lens and prevent the protein aggregation that would otherwise produce lens cataracts, the leading cause of human blindness. There are conflicting data in the literature as to what role the α-crystallins may play in early lens development. In this study, we used CRISPR gene editing to produce zebrafish lines with mutations in each of the three α-crystallin genes (cryaa, cryaba and cryabb) to prevent protein production. The absence of each α-crystallin protein was analyzed by mass spectrometry, and lens phenotypes were assessed with differential interference contrast microscopy and histology. Loss of αA-crystallin produced a variety of lens defects with varying severity in larvae at 3 and 4 dpf but little substantial change in normal fiber cell denucleation. Loss of αBa-crystallin produced no substantial lens defects. Our cryabb mutant produced a truncated αBb-crystallin protein and showed no substantial change in lens development. Mutation of each α-crystallin gene did not alter the mRNA levels of the remaining two, suggesting a lack of genetic compensation. These data suggest that αA-crystallin plays some role in lens development, but the range of phenotype severity in null mutants indicates its loss simply increases the chance for defects and that the protein is not essential. Our finding that cryaba and cryabb mutants lack noticeable lens defects is congruent with insubstantial transcript levels for these genes in lens epithelial and fiber cells through five days of development. Future experiments can explore the molecular mechanisms leading to lens defects in cryaa null mutants and the impact of αA-crystallin loss during zebrafish lens aging.

Reduction in Lens Epithelial Cell Senescence Burden through Dasatinib plus Quercetin or Rapamycin Alleviates D-Galactose-Induced Cataract Progression

Senescent cells accumulate in aged organisms and promote the progression of age-related diseases including cataracts. Therefore, we aimed to study the therapeutic effects of senescence-targeting drugs on cataracts. In this study, a 28-day D-galactose-induced cataract rat model was used. The opacity index, a grading based on slit-lamp observations, was used to assess lens cloudiness. Furthermore, the average lens density (ALD), lens density standard deviation (LDSD), and maximum lens density (MLD) obtained from Scheimpflug images were used to assess lens transparency. Immunohistochemical stainings for p16 and γH2AX were used as hallmarks of senescence. We treated rat cataract models with the senolytic drug combination dasatinib plus quercetin (D+Q) and senescence-associated secretory phenotype (SASP) inhibitors. In comparison to control lenses, D-galactose-induced cataract lenses showed a higher opacity index, ALD, LDSD, and MLD values, as well as accumulation of senescent lens epithelial cells (LECs). After D+Q treatment, ALD, LDSD, and MLD values on day 21 were significantly lower than those of vehicle-treated model rats. The expression levels of p16 and γH2AX were also reduced after D+Q administration. In addition, the SASP inhibitor rapamycin decreased the opacity index, ALD, LDSD, and MLD values on day 21. In conclusion, D+Q alleviated D-galactose-induced cataract progression by reducing the senescent LEC burden in the early stage of cataract.

Imaging Cataract-Specific Peptides in Human Lenses.

Age-related protein truncation is a common process in long-lived proteins such as proteins found in the ocular lens. Major truncation products have been reported for soluble and membrane proteins of the lens, including small peptides that can accelerate protein aggregation. However, the spatial localization of age-related protein fragments in the lens has received only limited study. Imaging mass spectrometry (IMS) is an ideal tool for examining the spatial localization of protein products in tissues. In this study we used IMS to determine the spatial localization of small crystallin fragments in aged and cataractous lenses. Consistent with previous reports, the pro-aggregatory αA-crystallin 66-80 peptide as well as αA-crystallin 67-80 and γS-crystallin 167-178 were detected in normal lenses, but found to be increased in nuclear cataract regions. In addition, a series of γS-crystallin C-terminal peptides were observed to be mainly localized to cataractous regions and barely detected in transparent lenses. Other peptides, including abundant αA3-crystallin peptides were present in both normal and cataract lenses. The functional properties of these crystallin peptides remain unstudied; however, their cataract-specific localization suggests further studies are warranted.

Identification and quantification of ionising radiation-induced oxysterol formation in membranes of lens fibre cells

Ionising radiation (IR) is a cause of lipid peroxidation, and epidemiological data have revealed a correlation between exposure to IR and the development of eye lens cataracts. Cataracts remain the leading cause of blindness around the world. The plasma membranes of lens fibre cells are one of the most cholesterolrich membranes in the human body, forming lipid rafts and contributing to the biophysical properties of lens fibre plasma membrane. Liquid chromatography followed by mass spectrometry was used to analyse bovine eye lens lipid membrane fractions after exposure to 5 and 50 Gy and eye lenses taken from wholebody 2 Gy-irradiated mice. Although cholesterol levels do not change significantly, IR dose-dependant formation of the oxysterols 7β-hydroxycholesterol, 7-ketocholesterol and 5, 6-epoxycholesterol in bovine lens nucleus membrane extracts was observed. Whole-body X-ray exposure (2 Gy) of 12-week old mice resulted in an increase in 7β-hydroxycholesterol and 7-ketocholesterol in their eye lenses. Their increase regressed over 24 h in the living lens cortex after IR exposure. This study also demonstrated that the IR-induced fold increase in oxysterols was greater in the mouse lens cortex than the nucleus. Further work is required to elucidate the mechanistic link(s) between oxysterols and IR-induced cataract, but these data evidence for the first time that IR exposure of mice results in oxysterol formation in their eye lenses.

Alternatives for corneal endothelial tissue engineering

AbstractCorneal endothelial diseases are common almost everywhere in the world and have 3 main origins: primary diseases, largely dominated by Fuchs' endothelial corneal dystrophy (FECD), iatrogenic diseases which mainly complicate lens surgery, whether cataract or clear lens, but also other surgeries. The frequency of these complications is very low but the number of these surgeries being gigantic (probably around 50 million cases/year/worlwide), the number of post‐surgical bullous keratopathy remains important. Post‐keratoplasty endothelial failure (early or late) is the 3rd cause.All these diseases “consume” 50% of corneal grafts in the world and a large part of the population does not have access to any graft. The number of corneal donors is absolutely insufficient to meet the world demand and corneal bioengineering appears to be a realistic solution to complete the offer. Because of its relative simplicity and the demonstrated effectiveness of endothelial keratoplasty, endothelial bioengineering is logically the first to be developed. The Japanese team of 2 Kyoto universities (Prof. S. Kinoshita, N. Koizumi and N. Okumura) is a pioneer in this field and has demonstrated the effectiveness of injection therapy, which consists of cultivating mature endothelial cells from a small number of corneas from young donors, then injecting them into the anterior chamber of patients. The industrialization of the process is underway in 2 different start‐ups, one in the United States, the other in Japan. In addition to injection therapy, the bioengineering of endothelial grafts (Tissue engineered endothelial keratoplasty, TEEK), which consists of cultivating endothelial cells on a “corneo‐compatible” carrier to exactly reproduce a DMEK or a DSAEK, has passed the preclinical stage. This presentation will detail these different processes, their current limitations and the short, medium and long term perspectives. These Advanced Therapy Medicinal products (ATMP) are clearly revolutionizing corneal transplantation. By offering a new treatment for endothelial diseases, they will make it possible to redirect donor corneas to other corneal diseases that have no therapeutic alternative. Finally, this paper will also discuss the prospects of medical and medico‐surgical treatments for FECD, which are at the frontier of endothelial bioengineering.

Visual Outcome of Phacoemulsification at Griya Husada Eye Center, Madiun, Indonesia

Introduction: Sight is one of the most important senses that absorbs more than 80% of visual information. However, visual disturbances are common, ranging from mild to severe disturbances that can lead to blindness. A cataract is the leading cause of blindness in Indonesia; it is accountable for 77.7% of all blindness. Phacoemulsification is a new ECCE technique in which cloudy or cataractous lenses are removed through a 2-3 mm incision with no sutures. The advantages of this small incision are faster visual recovery, minimal astigmatic induction due to surgery, and minimal postoperative complications and inflammation. Purpose: This study aimed to measure visual outcomes in senile cataract patients after phacoemulsification surgery at Griya Husada Eye Center, Madiun, Indonesia. Methods: A Retrospective study was carried out among senile cataract patients who had phacoemulsification surgery at Griya Husada Eye Center, Madiun, Indonesia between January and May 2021. The best corrected visual acuity (BCVA) was recorded on the fourteenth day. Results: From 292 patients, postoperative visual acuity in the good category (6/6 - 6/18) was 94.9%, in the moderate category (<6/18 - 6/60) was 1.7%, and in the poor category (<6/60) was 3.4%. Conclusions: Postoperative visual acuity with phacoemulsification at Griya Husada Eye Center, Madiun, Indonesia showed satisfactory results and met World Health Organization’s (WHO) standards.

Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract.

Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to investigate the therapeutic effects of histone acetyltransferase (HAT) inhibitors. Among the tested HAT inhibitors, TH1834 was the only one that could reverse most of the opacity once it had formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. In lens cross-sections, vacuoles were present in the tissue of the cortical equatorial region of untreated cataract samples. In treated cataract samples, lens tissue regenerated to fill the vacuoles. To identify the genes regulated by HAT inhibitors, qRT-PCR was performed on treated and untreated cataract samples to determine candidate genes. Expression of Acta1 and Stmn4, both of which are involved in the cytoskeleton, were altered significantly in C646+CPTH2 samples. Expression of Emd, a nuclear membrane protein, and Prtfdc1, which is involved in cancer cell proliferation, were altered significantly in CBP30+CPTH2 samples. Acta1, Acta2, Arrdc3, Hebp2, Hist2h2ab, Pmf1, Ppdpf, Rbm3, RGD1561694, Slc16a6, Slfn13, Tagln, Tgfb1i1, and Tuba1c in TH1834 samples were significantly altered. These genes were primarily related to regulation of cell proliferation, the cytoskeleton, and cell differentiation. Expression levels increased with the onset of cataracts and was suppressed in samples treated with HAT inhibitors.

A clinical case of a surgical treatment of complicated cataract in a patient with Hall–Hittner syndrome

Background: Variants of the CHD7 gene found in the OMIM 608892 genomic material are present in 8395% of patients suffering from the CHARGE syndrome. The aim of this report is to evaluate the clinical and functional results of cataract phacoemulsification with implantation of a toric intraocular lens in a patient with a very rare pathology HallHittner syndrome. Clinical case description: Under observation was patient V., who successfully underwent cataract phacoemulsification on the right eye with implantation of an intraocular lens for complicated cataract against the background of combined congenital eye pathology confirmed by the diagnostic data before and after the surgery. The optimal visual functions were reached after the successful surgical treatment. The patient was subjectively satisfied with the restored visual functions in the right eye. Conclusion: The clinical case demonstrates a successful implementation of cataract phacoemulsification with implantation of a toric intraocular lens in a patient diagnosed with complicated cataract against the background of combined congenital eye pathology, which suggests the possibility of a surgical treatment for such patients.

Spectral domain oct for screening of macular diseases prior to multifocal intraocular lens implantation

BackgroundCataract surgery with multifocal IOLs could give patients good vision and great satisfaction, at the same time generating high expectations; therefore, its precise indication is essential if we are to reach our goal. The use of optical coherence tomography may be a valuable tool in the screening of macular diseases, which often cannot be detected in routine clinical examinations. This study evaluates the benefit of including spectral domain optical coherence tomography (SD-OCT) in routine preoperative cataract surgery protocols for better case selection in multifocal IOLs.MethodsObservational and retrospective clinical study that includes patients with an indication for multifocal IOL implantation who underwent retinal fundus exam and SD-OCT examination between 2018 and 2019. The clinical examination with ophthalmoscopy and SD-OCT imaging results were evaluated to observe their influence on the final choice of the lens implanted lens in cataract surgery.Results405 eyes from 207 patients with multifocal IOL indication were included. It was found that 220 (54.2%) of all indicated multifocal or trifocal IOLs were in fact implanted. The most important reason for not implanting the indicated IOL was financial, in 116 (59.46%) eyes. The second cause were retinal abnormalities detected by SD-OCT, 63 eyes (15.6%). Those abnormalities included dry age-related macular degeneration (AMD) (50.7%), neovascular AMD (3.1%), vitreomacular adhesion (11.1%), diabetic macular edema (3.1%), epiretinal membrane (ERM) (25.3%) and other macular abnormalities (6.3%). Of the 63 eyes with an abnormal SD-OCT result, 44 (69.8%) were also identified by fundus examination. Nineteen (30.2%) eyes had abnormalities detected only by SD-OCT imaging with a normal clinical exam.ConclusionsRoutine use of SD-OCT imaging may help diagnose pre-existing macular pathologies not identified by clinical exam, helping both physicians and patients choose the ideal IOL individually and has the potential to prevent unsatisfactory functional results.

Expression of oxysterols in human lenses: Implications of the sterol pathway in age-related cataracts

Lanosterol, an oxysterol molecule, has been proposed to help maintain lens transparency by inhibiting the formation of protein aggregates. This sterol is produced by the enzyme lanosterol synthase and is part of a metabolic pathway that forms cholesterol as a final step. Abnormalities in lanosterol synthase are responsible for congenital cataracts. The αA-crystallin protein, which acts as a molecular chaperone to lanosterol synthase, has been reported to have anti-protein aggregation, anti-inflammatory and anti-apoptotic properties. In this work, we evaluated the correlation of lanosterol synthase and αA-crystallin in human cataractous lenses with the grade of opacity, as well as the expression of lanosterol synthase, farnesyl DPP, geranyl synthase and squalene epoxidase genes. Lanosterol synthase and αA-crystallin were overexpressed in cataractous lenses as well as farnesyl-DP synthase, squalene epoxidase, lanosterol synthase and geranyl synthase genes in cataratous lenses in comparison with normal lenses. Our data confirm that lanosterol synthase and the sterol pathway are upregulated in cataractous lenses. This argues for a functional role of the oxysterol pathway and its products as an important mediator in the pathogenesis of human cataracts.

Radiation induced cataracts in interventionalists occupationally exposed to ionising radiation.

BackgroundOccupational exposure to ionising radiation may have detrimental health effects. Longer and more complex fluoroscopic procedures have placed interventionalists at increased occupational health risks especially for developing cataracts in the radiosensitive lenses of the eyes.ObjectivesThis study aimed to determine the prevalence of occupational related cataracts and describe the risk factors for cataracts in occupationally exposed interventionalists compared with unexposed doctors.MethodA cross-sectional study using multiple methods. A survey was conducted. The radiation workload was determined based on a self-administered questionnaire and dose area product values determined in previous studies. Both groups had slit lamp examinations. The data were analysed analytically using R software version 9.3.ResultsThe study included 98 interventionalists. The combined prevalence of posterior sub-capsular (PSC) and cortical cataracts was 18.8% in the exposed and 13.9% in the unexposed group. The prevalence of PSC cataracts in the exposed group was 5.9% and 2.8% in the unexposed group, with an odds ratio (OR) of 2.2 (95% confidence interval [CI]: 0.58; 8.61). Posterior sub-capsular cataracts were more common in the left eye. The increase in cataracts was not statistically significant in the exposed group but is of clinical significance.ConclusionThe findings are important as they highlight the need for greater vigilance for protecting the radiation healthcare workforce in a developing country setting.ContributionThe research is the first of its kind in South Africa and Africa and contributes to determining the prevalence in this highly skilled and occupationally vulnerable group.

Binding of Alpha-Crystallin to Cortical and Nuclear Lens Lipid Membranes Derived from a Single Lens.

Several studies reported that α-crystallin concentrations in the eye lens cytoplasm decrease with a corresponding increase in membrane-bound α-crystallin with age and cataracts. The influence of the lipid and cholesterol composition difference between cortical membrane (CM) and nuclear membrane (NM) on α-crystallin binding to membranes is still unclear. This study uses the electron paramagnetic resonance (EPR) spin-labeling method to investigate the α-crystallin binding to bovine CM and NM derived from the total lipids extracted from a single lens. Compared to CMs, NMs have a higher percentage of membrane surface occupied by α-crystallin and binding affinity, correlating with less mobility and more order below and on the surface of NMs. α-Crystallin binding to CM and NM decreases mobility with no significant change in order and hydrophobicity below and on the surface of membranes. Our results suggest that α-crystallin mainly binds on the surface of bovine CM and NM and such surface binding of α-crystallin to membranes in clear and young lenses may play a beneficial role in membrane stability. However, with decreased cholesterol content within the CM, which mimics the decreased cholesterol content in the cataractous lens membrane, α-crystallin binding increases the hydrophobicity below the membrane surface, indicating that α-crystallin binding forms a hydrophobic barrier for the passage of polar molecules, supporting the barrier hypothesis in developing cataracts.

Study of Risk Factors Associated with Age Related Macular Degeneration in North Indian Population

Introduction: Age-related macular degeneration ARMD is becoming the leading cause of visual impairment. As the size of elderly population is rising in developing countries. To prevent the ARMD and enhance functioning of these persons the knowledge of ris factors are very important. Material and Method: The study includes 156 patients out of which 50 patients of ARMD and 106 controls all patient’s demographic data was recorded and clinical history and examination undertaken all the patients interview to obtain medical residential occupational and smoking history blood pressure visual acuity height weight and refractive error were measured. Detailed ocular examination with the help of indirect of thermos was done and grid and fluorescent angiography done for all patients. Result: ARMD was most common in 61-70 years age group (40%). 32% of ARMD patients were labor 30% were farmer maximum number 32% of ARMD where illiterate education status was not found to be statistically significant P > 0.9 prevalence of AR MD was higher in hypermetropia 74.07% 22.22% myopia 3.71% was emetropia (P<0.001). Among hyperopia 32% of AR MD patient have refractive error of +2 to +3 D (p< 0.05). 58% of ARMD patient were smokers (P<0.05). Conclusion: The study found age is the most significant refactor for ARMD. Other significant risk factors were hyperopia, smoking, obesity and high blood pressure. Cataractous lens and colour of iris was not found to be significant risk factors for ARMD patients.

Inhibitory effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.

ABSTRACTBackgroundTo evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.MethodsNine elder cynomolgus monkeys were used, consisting of three monkeys without cataract as controls, three monkeys with naturally occurring cortical cataract, and three monkeys with nuclear cataract as intervention groups. Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract. Fluorescence changes of injected thermogel and cataract progression were observed. Lanosterol concentration in aqueous humor, solubility changes in lens proteins, and oxidative stress levels were analyzed in the lenses of the control and intervention groups.ResultsInjected thermogel showed decreased fluorescence during follow up. Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased, which was in accordance with the changes in cortical lens clarity. However, lenses with nuclear opacification showed little change. In the cortical region of lenses with cortical cataract, solubility of α-crystallin was significantly increased after administration of lanosterol, as well as the reduction of oxidative stress.ConclusionsWe demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates. Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages, possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status. Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.

Preventive Effects of Vitamin C on Cataracts: In Vivo Study

Background: A cataract is a disease caused by various factors, one of which is the aging process. With increasing age, the formation of free radicals will cause pathological reactions in the lens and other toxic compounds, resulting in oxidative reactions. Administration of vitamin C injection as an antioxidant can reduce the reactivity of free radicals caused by oxidative reactions in cataract lenses induced by sodium selenite. This study aims to determine the preventive effect of vitamin C administration on selenite-induced cataracts based on the value of malondialdehyde (MDA) levels.
 Methods: The experimental study used 30 rats which were then divided into 5 treatment groups (P1, P2, P3, P4, and P5). Lenses were extracted for the measurement of malondialdehyde. The value of MDA levels was then analyzed using the One-way ANOVA statistical test.
 Results: Statistically, there was no significant difference in MDA levels in each treatment group. Analysis of the difference in mean MDA between the 2 groups showed that the average MDA levels of mice in groups P4 and P5 were relatively lower than P2 and P3, but higher than P1.
 Conclusion: Giving vitamin C was able to reduce MDA levels (a marker of oxidative stress) better than the group that did not receive vitamin C, but not statistically different.

A Study of Diabetic and Non-diabetic Human Cataract Lens by Scanning Electron Microscopy

Published on:August 2022Journal of Young Pharmacists, 2022; 14(3):302-304Original Article | doi:10.5530/jyp.2022.14.59 Authors:Swathy Govindaswamy1,*, Dhivya Sundaram21Department of Pharmacy Practice, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, INDIA.2Department of Biomedical Science, Bharathidasan University, Tiruchirappalli, Tamil Nadu, INDIA. Abstract:Background: This research aimed to ascertain the differences in morphological manifestation in the human diabetic cataractous lens compared to a non-diabetic cataractous lens by Scanning Electron Microscopy (SEM). Materials and Methods: Lens fibers were prefixed in glutaraldehyde and subsequently post-fixed in a Hexamethyldisilazane and examined by SEM. The SEM images gave a comparative morphological impression of the ongoing structural alterations during the degeneration process of human non-diabetic cataracts and diabetic cataract lenses. Results: Diabetic cataractous lens fibers were identified by more chaotic longitudinal fiber splitting, porosity, and granulation of the lens fiber membrane and opening (distortion) of the lens fiber interdigitation system than their non-cataractous diabetic counterparts. Diabetic cataract lenses showed an increased rate of nucleus compaction compared to non-diabetic cataract lenses. Conclusion: The absence of Finger-like and flap projections and the disappearance of the ball and socket system is prominent in diabetic cataract lenses, suggesting the hyperglycaemic effect in the degeneration of lens fibers and further contributes to the early onset of cataracts in diabetes compared to non-diabetic.Keywords: Cataract, Diabetic complications, Morphology, Scanning electron microscopy.

Molecular dynamics simulations of the human ocular lens with age and cataract

The human ocular lens consists primarily of elongated, static fibers characterized by high stability and low turnover, which differ dramatically in their composition and properties from other biological membranes. Cholesterol (Chol) and sphingolipids (SL) are present at high concentrations, including saturated SLs, such as dihyrosphingomyelin (DHSM). Past molecular dynamics simulations demonstrated that the presence of DHSM and high Chol concentration contributes to higher order in lipid membranes. This current study simulated more complex models of human lens membranes. Models were developed representing physiological compositions in cataractous lenses aged 74 ± 6 years and in healthy lenses aged 22 ± 4, 41 ± 6, and 69 ± 3 years. With older age, Chol and ceramide concentrations increase and glycerophospholipid concentration decreases. With cataract, ceramide concentration increases and Chol and glycerophospholipid concentrations decrease. Surface area per lipid, deuterium order parameters (SCD), sterol tilt angle, electron density profiles, bilayer thickness, chain interdigitation, two-dimensional radial distribution functions (2D-RDF), lipid clustering, and hydrogen bonding were calculated for all simulations. All systems exhibited low surface area per lipid and high bilayer thickness, indicative of strong vertical packing. SCD parameters suggest similarly, with saturated tails in the hydrophobic core of the membrane having elevated order. Vertical packing and acyl tail order increased with both age and cataract condition. Lateral diffusion decreased with age and cataracts, with the older and cataractous models demonstrating increased long-range structure by the 2D-RDF analysis. In future work examining the membrane proteins of the lens, these models can serve as a physiologically accurate representation of the lens lipidome.

Evaluation of the Rheological Properties, Preclinical Safety, and Clinical Effectiveness of a New Dispersive Ophthalmic Viscoelastic Device for Cataract Surgery.

PurposeTo evaluate the rheological properties of the ophthalmic viscoelastic device (OVD) PRO-149, its preclinical safety, and its effectiveness when used during cataract surgery in patients with age-related cataract.Material and MethodsControl (HEC) and test (PRO-149) OVDs were compared through rheological measures, by two preclinical safety studies in rabbits, and under normal-use conditions during cataract removal and lens implantation in a parallel randomized clinical trial.ResultsRheological properties were determined. Preclinical studies did not find any evidence of safety issues or toxicity. In the clinical trial, 36 subjects were included. After 29 days, there were no statistically significant differences in mean percentage of endothelial cell count change or in the postoperative intraocular pressure between groups. There were no significant differences between OVDs for any safety parameter studied. Finally, PRO-149 showed a statistically significant improvement in surgeon rating for ease of use during extraction (p < 0.05).ConclusionPRO-149 is a dispersive OVD. The rabbit models did not find evidence of clinical alterations or toxicity. The results of the clinical study support that the two studied OVDs were clinically similar in terms of safety and effectiveness for cataract surgery.Trial RegistrationThe trial is registered at Clinical Trials.gov at NCT04702802 (21–01-11).

Optical Memory Effect of excised cataractous human crystalline lenses

Optical Memory Effect of excised cataractous human crystalline lenses