Comparison of Transcriptomic Analysis of the Conjunctiva in Glaucoma-Treated Eyes with Dry Eyes and Healthy Controls

Ocular surface disease (OSD) associated with topical glaucoma drugs is a common issue impacting treatment adherence. We aimed to identify conjunctival transcriptomic changes in glaucoma and dry eye patients, comparing them to healthy controls. Bulbar conjunctival specimens were collected via impression cytology from 33 patients treated for glaucoma, 9 patients with dry eye, and 14 healthy controls. RNA extraction and bulk RNA sequencing were performed, followed by bioinformatics analysis to detect gene dysregulation. Ingenuity pathways analysis (IPA) identified pathways and biological processes associated with these transcriptomic changes. Sequencing analysis revealed 200 modified genes in glaucoma patients compared to healthy individuals, 233 differentially expressed genes in dry eye patients versus controls, and 650 genes in treated versus dry eye samples. In glaucoma patients, 79% of altered pathways were related to host defense, while dry eye patients showed a 39% involvement of host response, 15% in cellular proliferation and integrity, and 16% of mitochondrial dysfunction. These findings were validated through qRT-PCR. Glaucoma patients showed an intensified conjunctival immune response as a potential cause of OSD, whereas in dry eye patients, in addition to the immune response, other mechanisms such as mitochondrial dysfunction or reduced cellular proliferation were observed

Technological advances in ocular trabecular meshwork in vitro models for glaucoma research

Glaucoma is the leading cause of irreversible blindness worldwide and ischaracterized by the progressive degeneration of the optic nerve. Intraocularpressure (IOP), which is considered to be the main risk factor for glaucomadevelopment, builds up in response to the resistance (resistance to what?) providedby the trabecular meshwork (TM) to aqueous humor (AH) outflow. Although theTMand its relationship to AH outflow have remained at the forefront of scientificinterest, researchers remain uncertain regarding which mechanisms drive thedeterioration of the TM. Current tissue‐engineering fabrication techniques havecome up with promising approaches to successfully recreate the TM. Nonetheless,more accurate models are needed to understand the factors that make glaucomaarise. In this review, we provide a chronological evaluation of the technologicalmilestones that have taken place in the field of glaucoma research, and we conduct acomprehensive comparison of available TM fabrication technologies. Additionally,we also discuss AH perfusion platforms, since they are essential for the validation ofthese scaffolds, as well as pressure–outflow relationship studies and the discovery ofnew IOP‐reduction therapies

Loss of the matrix metalloproteinase-10 causes premature features of aging in satellite cells

Aged muscles accumulate satellite cells with a striking decline response to damage. Although intrinsic defects in satellite cells themselves are the major contributors to aging-associated stem cell dysfunction, increasing evidence suggests that changes in the muscle-stem cell local microenvironment also contribute to aging. Here, we demonstrate that loss of the matrix metalloproteinase-10 (MMP-10) in young mice alters the composition of the muscle extracellular matrix (ECM), and specifically disrupts the extracellular matrix of the satellite cell niche. This situation causes premature features of aging in the satellite cells, contributing to their functional decline and a predisposition to enter senescence under proliferative pressure. Similarly, reduction of MMP-10 levels in young satellite cells from wild type animals induces a senescence response, while addition of the protease delays this program. Significantly, the effect of MMP-10 on satellite cell aging can be extended to another context of muscle wasting, muscular dystrophy. Systemic treatment of mdx dystrophic mice with MMP-10 prevents the muscle deterioration phenotype and reduces cellular damage in the satellite cells, which are normally under replicative pressure. Most importantly, MMP-10 conserves its protective effect in the satellite cell-derived myoblasts isolated from a Duchenne muscular dystrophy patient by decreasing the accumulation of damaged DNA. Hence, MMP-10 provides a previously unrecognized therapeutic opportunity to delay satellite cell aging and overcome satellite cell dysfunction in dystrophic muscles

SEAwise Report on improved predictive models of growth, production and stock quality.

The SEAwise project works to deliver a fully operational tool that will allow fishers, managers, and policy makers to easily apply Ecosystem Based Fisheries Management (EBFM) in their fisheries and understanding how ecological drivers impact stock productivity through growth, condition and maturity is essential to this proces. In this SEAwise report, we present the predictive models of fish growth, condition and maturity obtained so far in each of the four regional case studies.The biological processes (fish growth, condition and maturity) were studied in terms of body size (weight-at-age, length-at-age), condition factor, otolith increments and size at first maturity. Underlying data were available at different levels, ranging from individual fish, to sampling haul or stock level. Accordingly, the methods employed varied across case studies to adapt to the specific features of the process under study and the available data.The methodology encompassed statistical models (linear models, generalised additive models, mixed models, Bayesian nested hierarchical models, changepoint models), otolith growth increment analyses and mechanistic models (DEB-IBM model coupled to the environment and mizer model). Some of these models were focused on detecting overall trends, including potential changepoints along the time series or identification of the main intrinsic factors. Other models explored the impact of ecological drivers such as temperature, salinity, food availability or density dependence.In the Baltic Sea, two regimes were identified in the weight-at-age time series of herring in the Gulf of Riga (1961-1988 and 1989-2020). During the first period the main driver of the individual annual growth of the fish was the abundance of the copepod L. macrurus macrurus, while the abundance of the adult stages of E. affinis affinis was the dominating explanatory variable affecting herring growth during the second period. Neither SSB nor summer temperature during the main feeding period were significant drivers of the individual growth in the two distinct ecosystem regimes.In the Mediterranean Sea, the analysis of the impact of the environmental variables on biological parameters like size at first maturity, condition factor and growth in South Adriatic Sea and North-West Ionian Sea showed some significant effects in relation to the different species/area. In most of the cases, the environmental driver was bottom temperature, although some relationships with bottom salinity and primary production were also found. The model outcomes suggested that temperatures prevailing in deeper waters were the most significant factor affecting gonad maturity of hakes, while those in the shallow zone had the main impact on the L50 of red mullets. Condition factor of hake and red mullet in the Eastern Ionian Sea were affected not only by temperature, but also by zooplankton abundance.In the North Sea, mediated length-based growth models, linear mixed models and state-space linear mixed models were applied to four gadoids, two flatfishes and one pelagic stock and their performances were assessed in terms of model fit and predictive capability. For the mediated length-based growth model approach, the best model differed across stocks, but density dependent mediation effects were significant for five out of the seven stocks. Regarding the linear mixed models, the two types of models and the different penalisation procedures led to different models across stocks. Among the additional ecological variables, surface temperature was the most frequently included in the final model, closely followed closely by SSB and to a lesser extent by NAO. Detailed otolith increment analysis was used in the development of multidecadal biochronologies of average annual growth of sole in the North Sea and in the Irish Sea. In the North Sea, the best extrinsic model of sole growth included sea bottom temperature, fishing mortality at age, and stock biomass at maturity stage, and their interactions with age and maturity stage, while in the Irish Sea, the best extrinsic model included sea bottom temperature and fishing mortality at maturity stage and its interaction with maturity stage. These results confirmed the expected positive effect of temperature on adult growth. However, in the North Sea, temperature showed unexpected negative effect on juvenile growth, which might be linked to changes in food availability and/or intraspecific competition and need to be further studied. The mizer model (package for size-spectrum ecological modelling) with environmental forcing was used to study whether warming in the North Sea is responsible for the failure of the cod stock. The simulated fish community response when recruitment and carrying capacity depended on surface temperature fitted better with the assessment data than when the environment was fixed. However, the qualitative differences remain, suggesting that temperature effects were not the main cause of the model-assessment disparity.In the Western Waters, the mediated length-based growth models developed for the North Sea case study were applied to 14 stocks in the Celtic Sea. The best model differed across stocks, but again SSB mediation was significant for most of the stocks. From visual inspection of the plots, however, it was noted that the raw data from certain stock objects showed a reduced growth compared to the model fits, requiring further analyses. The analysis on biological measurements of individuals collected at fish markets, observers at sea or during scientific cruises allowed to study temporal variations in body size and condition factor of benthic, pelagic and demersal species in the Celtic Sea and the Bay of Biscay. The linear models indicated a significant negative monotonic relationship of sizes at all ages for anchovy and pilchard, but variations in size at age were less clear and significant for benthic and demersal species. In contrast, the results of the body condition indices showed a moderate but significant decrease for all the studied 19 species over time. The in-depth analysis for anchovy in the Bay of Biscay based on research surveys confirmed the decline in the length and weight of anchovy in the Bay of Biscay and pointed to a decline in body condition toward slender body shapes. Detected associations between temperature and size became more apparent for adult age classes than for juveniles, whereas the association between anchovy size and the biomass of spawners was more important for juvenile than for adult age classes. Associations between anchovy size and chlorophyll-a concentration were in general weak. Finally, the DEB-IBM model coupled to the environment that is under development for the two main seabass stocks of the North East Atlantic will provide further insights on how growth, condition and maturation can affect the future dynamics and productivity of these stocks.Read more about the project at www.seawiseproject.org</p