Biochim Biophys Acta Mol Basis Dis
October 2023
The alternative oxidase, AOX, provides a by-pass of the cytochrome segment of the mitochondrial respiratory chain when the chain is unavailable. AOX is absent from mammals, but AOX from Ciona intestinalis is benign when expressed in mice. Although non-protonmotive, so does not contribute directly to ATP production, it has been shown to modify and in some cases rescue phenotypes of respiratory-chain disease models.
View Article and Find Full Text PDFPurpose: The aims of this study were to determine national-level trends in early regraft rates and examine patient-level and surgeon-level characteristics associated with early regrafts.
Methods: This was a retrospective, cohort study. We identified beneficiaries aged 65 years or older in the 2011 to 2020 Medicare carrier claims data set who underwent Endothelial keratoplasty (EK) and subsequently underwent an early regraft.
The fundamental body functions that determine maximal O uptake (V̇o) have not been studied in Aqp5 mice (aquaporin 5, AQP5). We measured V̇o to globally assess these functions and then investigated why it was found altered in Aqp5 mice. V̇o was measured by the Helox technique, which elicits maximal metabolic rate by intense cold exposure of the animals.
View Article and Find Full Text PDFCurrent concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice.
View Article and Find Full Text PDFMitochondrial disorders are clinically and genetically diverse, with isolated complex III (CIII) deficiency being relatively rare. Here, we describe two affected cousins, presenting with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycaemia and encephalopathy. Genetic investigations in both cases identified a homozygous deletion of exons 2 and 3 of UQCRH, which encodes a structural complex III (CIII) subunit.
View Article and Find Full Text PDFInfluenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are among the best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses in offspring. We establish a two-hit mouse model to study the effect of maternal influenza A virus infection (first hit) on vulnerability of offspring to heterologous infections (second hit) in later life.
View Article and Find Full Text PDFPurpose: The purpose of this study was to report trends in the prevalence of early graft failure after endothelial keratoplasty in the United States.
Methods: Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) graft volumes were collected from records maintained by 6 major eye banks in the United States from January 1, 2013, to December 31, 2018. The prevalence and presumed cause of early graft failures (defined as a graft with persistent edema or regrafted within 8 weeks after keratoplasty) each year were sourced from surgeon-reported adverse events.
Improving reproducibility and replicability in preclinical research is a widely discussed and pertinent topic, especially regarding ethical responsibility in animal research. INFRAFRONTIER, the European Research Infrastructure for the generation, phenotyping, archiving, and distribution of model mammalian genomes, is addressing this issue by developing internal quality principles for its different service areas, that provides a quality framework for its operational activities. This article introduces the INFRAFRONTIER Quality Principles in Systemic Phenotyping of genetically altered mouse models.
View Article and Find Full Text PDFPurpose: To ascertain whether death-to-preservation time (DPT) is associated with donor endothelial cell density (ECD), primary graft failure (PGF), and infection.
Methods: Donor corneas aged older than 10 years with ECD 2000 to 4500 cells/mm2 were procured between 2011 and 2018 by a single eye bank. Donor corneas were analyzed retrospectively for the main outcome measures of PGF, infection, and ECD.
Purpose: To describe the intraoperative and early postoperative complications using preloaded Descemet membrane endothelial keratoplasty (DMEK) grafts with intraocular injection of the graft in Optisol-GS and omission of trypan blue restaining.
Methods: This is a retrospective case series of 132 consecutive eyes with Fuchs endothelial dystrophy or endothelial failure who underwent DMEK using preloaded donor tissue prepared as previously described. The graft was not restained with trypan blue by the surgeon, and Optisol-GS was injected with the graft into the eye instead of being rinsed from the injector.
Using standardized guidelines in preclinical research has received increased interest in light of recent concerns about transparency in data reporting and apparent variation in data quality, as evidenced by irreproducibility of results. Although the costs associated with supporting quality through a quality management system are often obvious line items in laboratory budgets, the treatment of the costs associated with quality failure is often overlooked and difficult to quantify. Thus, general estimations of quality costs can be misleading and inaccurate, effectively undervaluing costs recovered by reducing quality defects.
View Article and Find Full Text PDFPurpose: To examine barriers and facilitators to adoption of Descemet membrane endothelial keratoplasty (DMEK) for treatment of endothelial dysfunction.
Methods: Anonymous electronic surveys were emailed to surgeons ordering corneal transplant tissue in the past 18 months from 2 eye banks in the United States (US).
Results: Of 365 surgeons emailed, 118 (32%) completed the survey.
Purpose: To identify donor and recipient factors, including eye bank tissue observations, predictive of operative complications in the Cornea Preservation Time Study.
Methods: One thousand three hundred thirty study eyes undergoing Descemet stripping automated endothelial keratoplasty for Fuchs dystrophy or pseudophakic/aphakic corneal edema were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (N = 675) or 8 to 14 days (N = 655). Donor factors included demographics, prelamellar corneal and postlamellar lenticule dissection thickness, central endothelial cell density, and tissue processing time.
Purpose: To examine the association of donor, recipient, and operative factors on graft dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS) as well as the effects of graft dislocation and elevated IOP on graft success and endothelial cell density (ECD) 3 years postoperatively.
Design: Cohort study within a multi-center, double-masked, randomized clinical trial.
Methods: 1090 individuals (1330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (6% of eyes).
Purpose: Previous work has suggested that Descemet membrane (DM) folds arise in response to corneal swelling. However, their origin has not been closely explored. In this study, we used optical coherence tomography to evaluate whether DM folds arise secondary to folds in the middle stroma.
View Article and Find Full Text PDFPurpose: To examine postoperative reports of infection rates for eye bank-prepared and non-eye bank-prepared corneas from January 1, 2006 to December 31, 2017, from a single eye bank.
Method: A retrospective review of reported fungal and bacterial infections with corneal transplant surgeries using corneas distributed by our eye bank was conducted. The reported number of infections for corneas that underwent eye bank preparation (pre-cut and pre-stripped corneas) and for those distributed without eye bank preparation was quantified.
Purpose: To compare tissue evaluation times and specular image quality before and after the implementation of rapid tissue warming at a single eye bank.
Methods: This retrospective study compares the evaluation of 494 donor corneas. All corneas were stored in Optisol-GS.
Purpose: Evaluation of cumulative Descemet membrane endothelial keratoplasty endothelial cell loss (ECL) from preparation through injection using 2 different glass injectors.
Methods: Eighteen Descemet membrane endothelial keratoplasty grafts with "S" stamps were prepared by eye bank technicians. Nine grafts were assigned to injection with a modified glass Jones tube injector with a 2.
Irradiated corneal tissues have been used for a variety of ophthalmic procedures including glaucoma drainage device covers and lamellar grafts. The maintenance of corneal clarity is important, as light obstructions resulting from processing or long-term storage of irradiated corneas may negatively affect vision and postoperative cosmesis. It has been reported that corneal tissues can be preserved in human serum albumin (HSA), however, the clarity of corneas after long-term storage in HSA has not been well described.
View Article and Find Full Text PDFPurpose: To examine the stability of postmortem glycated hemoglobin (HbA1c) measurement and its relationship to premortem glycemia.
Methods: Postmortem blood samples were obtained from 32 donors (8 known diabetic) and shipped on ice to a central laboratory to examine the stability of HbA1c measurements during the first 9 postmortem days. Thirty-nine other suspected diabetic donors underwent comparison of premortem and postmortem HbA1c measurements.
Purpose: To determine whether warming donor corneas to near-physiological temperatures can safely shorten warming times while providing high-quality specular images during tissue evaluation.
Methods: Mated corneas were warmed at room temperature (RT) or at 35°C for 4 hours upon removal from cold storage. Specular images and endothelial cell densities were acquired and rated every hour.