Metabolomic Disparities in Intraocular Fluid Across Varied Stages of Cataract Progression: Implications for the Analysis of Cataract Development.

Introduction: The lens's metabolic demands are met through a continuous circulation of aqueous humor, encompassing a spectrum of components such as organic and inorganic ions, carbohydrates, glutathione, urea, amino acids, proteins, oxygen, carbon dioxide, and water. Metabolomics is a pivotal tool, offering an initial insight into the complexities of integrated metabolism. In this investigative study, we systematically scrutinize the composition of intraocular fluid in individuals afflicted with cataracts. Methods: The investigation involved a comprehensive analysis of aqueous humor samples from a cohort comprising 192 patients. These individuals were stratified by utilizing the SPONCS classification system, delineating distinct groups characterized by the hardness of cataracts. The analytical approach employed targeted quantitative metabolite analysis using HILIC-based liquid chromatography coupled with high-resolution mass spectrometric detection. The metabolomics data analysis was performed with MetaboAnalyst 5.0. Results: The results of the enrichment analysis have facilitated the inference that the discerned disparities among groups arise from disruptions in taurine and hypotaurine metabolism, variations in tryptophan metabolism, and modifications in mitochondrial beta-oxidation of short-chain saturated fatty acids and pyrimidine metabolism. Conclusion: A decline in taurine concentration precipitates diminished glutathione activity, prompting an elevated requirement for NAD+ and instigating tryptophan metabolism along the kynurenine pathway. Activation of this pathway is additionally prompted by interferon-gamma and UV radiation, leading to the induction of IDO. Concurrently, heightened mitochondrial beta-oxidation signifies a distinctive scenario in translocating fatty acids into the mitochondria, enhancing energy production.

A Fermentation State Marker Rule Design Task in Metabolic Engineering.

There are several ways in which mathematical modeling is used in fermentation control, but mechanistic mathematical genome-scale models of metabolism within the cell have not been applied or implemented so far. As part of the metabolic engineering task setting, we propose that metabolite fluxes and/or biomass growth rate be used to search for a fermentation steady state marker rule. During fermentation, the bioreactor control system can automatically detect the desired steady state using a logical marker rule. The marker rule identification can be also integrated with the production growth coupling approach, as presented in this study. A design of strain with marker rule is demonstrated on genome scale metabolic model iML1515 of Escherichia coli MG1655 proposing two gene deletions enabling a measurable marker rule for succinate production using glucose as a substrate. The marker rule example at glucose consumption 10.0 is: IF (specific growth rate µ is above 0.060 h-1, AND CO2 production under 1.0, AND ethanol production above 5.5), THEN succinate production is within the range 8.2-10, where all metabolic fluxes units are mmol ∗ gDW-1 ∗ h-1. An objective function for application in metabolic engineering, including productivity features and rule detecting sensor set characterizing parameters, is proposed. Two-phase approach to implementing marker rules in the cultivation control system is presented to avoid the need for a modeler during production.

Pichia pastoris growth-coupled heme biosynthesis analysis using metabolic modelling.

Soy leghemoglobin is one of the most important and key ingredients in plant-based meat substitutes that can imitate the colour and flavour of the meat. To improve the high-yield production of leghemoglobin protein and its main component-heme in the yeast Pichia pastoris, glycerol and methanol cultivation conditions were studied. Additionally, in-silico metabolic modelling analysis of growth-coupled enzyme quantity, suggests metabolic gene up/down-regulation strategies for heme production. First, cultivations and metabolic modelling analysis of P. pastoris were performed on glycerol and methanol in different growth media. Glycerol cultivation uptake and production rates can be increased by 50% according to metabolic modelling results, but methanol cultivation-is near the theoretical maximum. Growth-coupled metabolic optimisation results revealed the best feasible upregulation (33 reactions) (1.47% of total reactions) and 66 downregulation/deletion (2.98% of total) reaction suggestions. Finally, we describe reaction regulation suggestions with the highest potential to increase heme production yields.

Crypthecodinium cohnii Growth and Omega Fatty Acid Production in Mediums Supplemented with Extract from Recycled Biomass.

Crypthecodinium cohnii is a marine heterotrophic dinoflagellate that can accumulate high amounts of omega-3 polyunsaturated fatty acids (PUFAs), and thus has the potential to replace conventional PUFAs production with eco-friendlier technology. So far, C. cohnii cultivation has been mainly carried out with the use of yeast extract (YE) as a nitrogen source. In the present study, alternative carbon and nitrogen sources were studied: the extraction ethanol (EE), remaining after lipid extraction, as a carbon source, and dinoflagellate extract (DE) from recycled algae biomass C. cohnii as a source of carbon, nitrogen, and vitamins. In mediums with glucose and DE, the highest specific biomass growth rate reached a maximum of 1.012 h-1, while the biomass yield from substrate reached 0.601 g·g-1. EE as the carbon source, in comparison to pure ethanol, showed good results in terms of stimulating the biomass growth rate (an 18.5% increase in specific biomass growth rate was observed). DE supplement to the EE-based mediums promoted both the biomass growth (the specific growth rate reached 0.701 h-1) and yield from the substrate (0.234 g·g-1). The FTIR spectroscopy data showed that mediums supplemented with EE or DE promoted the accumulation of PUFAs/docosahexaenoic acid (DHA), when compared to mediums containing glucose and commercial YE.

Biopharmaceutical-Type Chinese Hamster Ovary Cell Cultivation Under Static Magnetic Field Exposure: A Study of Genotoxic Effect.

The lack of a sufficient research base is the reason for the ongoing discussion regarding the genotoxic effect of magnetic field (MF) exposure on mammalian cell cultures. Chinese hamster ovary (CHO) suspension-type cells, which are widely used for biopharmaceutical production, are potentially subjected to an increased MF when cultivated in bioreactors equipped with bottom-placed magnetically coupled stirring mechanisms. The main challenge for conducting research in this field remains the availability of a suitable experimental setup that generates an appropriate MF for the raised research question. In the present study, a simple and cost-effective experimental setup was developed that generated a static MF, similar to what has been modeled in large-scale bioreactors and, at the same time, was suitable for experimental cell cultivation in laboratory conditions. The measured maximum magnetic flux density to which the cells were exposed was 0.66 T. To assess the possible genotoxic effect, cells were continuously subcultivated in laboratory petri dishes for a period of 14 days, corresponding to a typical duration of a biopharmaceutical production process in a conventional fed-batch regime. The genotoxic effect was assessed using the cytokinesis-block micronucleus assay with fluorescent staining. Results showed that a 0.66-T static MF exposure had no significant long-term effect on cell viability and chromosomal damage but demonstrated a short-term effect on cell apoptosis. Significant increase in nuclear bud formation was observed. These findings may encourage other researchers in future studies investigating cellular responses to MF exposure and contribute relevant data for comparison.

Isolated posterior capsule rupture after blunt eye injury.

Isolated posterior capsule rupture of the crystalline lens after blunt eye injury is a rare complication and demands a special surgical management strategy in order to achieve a good visual outcome.

Anterior Capsule Opening Contraction and Late Intraocular Lens Dislocation after Cataract Surgery in Patients with Weak or Partially Absent Zonular Support.

BACKGROUND AND OBJECTIVES: To evaluate anterior capsule opening (ACO) contraction and late intraocular lens (IOL) dislocation after cataract surgery in patients with weak or partially absent zonular support and assess methods of reducing these complications. MATERIALS AND METHODS: For this prospective study, we enlisted cataract surgery patients in our hospital with preoperative diagnoses of weak zonules. All patients received phacoemulsification surgery with implantation of a hydrophobic acrylic IOL and capsular tension ring (CTR). ACO reductions were measured for six months after enrolment. Data on late IOL dislocations were collected five years after enrolment of the last patient. RESULTS: Fifty-three patients were enrolled from 2011 to 2015. Over the six-month active follow-up period, ACO area reduction was 23% in patients receiving CTRs of 11 mm diameter and 8% for patients with CTRs of 12 mm, with an overall mean of 15% reduction. Five years after the last patient was enrolled, seven patients (13%) had experienced late IOL-CTR-capsular bag dislocation. For these patients, the mean ACO reduction in the first six months of follow-up was 33%, including for those who had received neodymium-doped yttrium aluminum garnet (Nd: YAG) anterior capsulotomies. CONCLUSION: Use of hydrophobic acrylic lenses and CTR reduces ACO contraction, with rates comparable to those after cataract surgery without ocular comorbidity. Our patients experienced a relatively high rate of late IOL-CTR-capsular bag dislocation. However, dislocated complexes were easily repositioned and few patients required IOL exchange. Frequent visits are warranted to promptly detect late complications of cataract surgery in patients with weak zonular support.

Long-Term Outcome of Cataract Surgery in Eyes with Pseudoexfoliation Syndrome Associated with Weak Zonules: A Case Report.

A cataract surgery in both eyes was scheduled for an 81-year-old female patient. However, ophthalmic examination revealed marked iridodonesis, phacodonesis and pseudoexfoliative material on the surface of the lens in both eyes indicating weak zonules caused by pseudoexfoliation syndrome, which was more pronounced in the left eye. Cataract surgery was performed initially in the left eye by phacoemulsification. Additionally, iris hooks and capsular tension ring (CTR) were used to stabilize the capsular bag, and the haptic of the intraocular lens (IOL) was sutured to the iris at the end of the surgery. The same procedure except haptic suturing was performed in the right eye after 6 months. The left eye remained stable, whereas the right eye developed considerable anterior capsular contraction 2 months postoperatively. Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy was performed to treat the condition. Moreover, 3 years after the initial surgery, late IOL-CTR-capsular-bag complex dislocation developed in the right eye, and reposition surgery was performed. Three days after IOL-CTR-capsular-bag complex reposition surgery, endophthalmitis developed; the eye responded well to 1 mg intravitreal vancomycin treatment. IOL in the right eye remained stable 3 years postoperatively.

Factors influencing myopic shift in children after intraocular lens implantation.

INTRODUCTION: Intraocular lenses have always been a controversial topic in pediatric cataract surgery. In the early 1990s in the post-Soviet states of Eastern Europe, intraocular lenses promised an easier full-time correction and amblyopia treatment. Since 1991, ophthalmologists in Latvia have been implanting intraocular lenses in infants. Amount of the postoperative myopic shift and its influencing factors, analyzed in this article, are important indicators of congenital cataract treatment. MATERIALS AND METHODS: A retrospective chart review off 85 children (137 eyes) who underwent foldable posterior chamber intraocular lens implantation at the Clinical University Hospital in Riga, Latvia, from 1 January 2006 until 31 December 2016, was performed. Depending on the age at surgery, patients were divided into six groups: 1-6, 7-12, 13-24, 25-48, 49-84, and 85-216 months. RESULTS: The largest and more variable myopic shift was found in a group of diffuse/total and nuclear cataract with surgery before the age of 6 months. There was a statistically significant correlation between the acquired best-corrected visual acuity and the amount of myopic shift (rs = 0.33; p < 0.001). Comparing the amount of myopic shift in two groups of different intraocular lens implantation target refraction tactics, we did not find statistically significant differences. Comparing the amount of myopic shift and implanted intraocular lens power, a negative, statistically significant correlation was found. CONCLUSION: The earlier the cataract extraction surgery and intraocular lens implantation is performed, the larger the myopic shift. The morphological type of cataract, best-corrected visual acuity, secondary glaucoma, and intraocular lens power influence the amount of myopic shift.

Anterior capsulorhexis opening reduction after cataract surgery with subluxated lenses.

BACKGROUND AND OBJECTIVE: This study sought to evaluate anterior capsulorhexis opening (ACO) reductions after surgery for a subluxated lens. Significant reduction of an ACO supports direct zonular involvement (capsular factors excluded by use of capsular tension rings [CTRs] and modern intraocular lens [IOLs]), and these findings question the long-term efficacy of subluxated lens surgery by means of cataract surgery. A small ACO due to lens mobility, non-enlargement of the ACO, and no lens epithelial cell washing due to an additional risk of further zonular damage were left as additional features to evaluate the possible outcomes of this simplified but still complicated surgery. MATERIALS AND METHODS: Data from 30 patients were used in the final analysis of this prospective study. Phacoemulsifications of subluxated lenses were performed in all patients, and iris/capsule hooks and CTRs or Cionni rings were used as stabilisers of the lens. Photography of the anterior parts (performed at 1 day, 1 week, 1 month, 3 months and 6 months after surgery) was used to evaluate the anterior capsulorhexis openings. RESULTS: Small initial anterior capsulorhexis openings (13.54mm2) were achieved, and the area reduction at 6 months was 16.70% (mean area at month 6: 11.28mm2, P<0.001). The reduction of the ACO area in the pseudoexfoliation (PEX) syndrome patients was 20% relative to the initial size (13.49mm2 vs. 10.92mm2, P<0.001). Two patients exhibited marked ACO reductions, and both were referred for anterior laser capsulotomy treatment. CONCLUSIONS: A weak or partially absent zonule does not markedly affect the reduction of the anterior capsule opening if appropriate surgical techniques, support materials and IOLs are used, even in the presence of a small initial capsulorhexis opening area. Therefore, a cataract surgery approach on the subluxated lens should be used. Ocular comorbidities, particularly PEX syndrome, play more significant roles in ACO reduction, and appropriate ACO size reducing inhibitors (e.g., anterior laser capsulotomy) or other types of surgery should be used.