A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery

Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo

Comparison of δ18O analyses on individual planktic foraminifer (Orbulina universa) shells by SIMS and gas-source mass spectrometry

The oxygen isotope (δ18O) compositions of final chamber fragments of individual shells of the planktic foraminifer Orbulina universa were measured in situ via secondary ion mass spectrometry (SIMS) and by traditional gas-source mass spectrometry (GSMS) entailing acid digestion of sampled calcite. The paired SIMS-GSMS analyses were performed on final chamber fragments of fossil shells taken from the top of a sediment core (Holocene) as well as shells grown in laboratory culture. Multiple iterations of SIMS-GSMS analyses were conducted on final chamber fragments treated with a variety of cleaning protocols. The series of paired analyses yielded an average SIMS-GSMS δ18O offset (Δ18OSIMS-GSMS) of −0.9 ± 0.1‰ (±2 SE). The volume of material analyzed in 10-μm SIMS spots is ~105 times smaller than that analyzed by GSMS; hence, the extent to which these Δ18OSIMS-GSMS values represent real differences in analyte vs. instrumental factors remains unclear. Possible contributing factors to the SIMS-GSMS δ18O difference include sample-standard mismatch by SIMS, differences in standardization of SIMS and GSMS, and non-calcite contaminants in samples. Although the two datasets are consistently offset, SIMS values reproduce inter-shell δ18O variability delineated by shell fragment GSMS values. This strong positive covariance proved useful for bringing the two datasets into agreement (i.e. Δ18OSIMS-GSMS = 0), and confirms that SIMS-based foraminifer δ18O values record changes in calcification temperature and/or δ18O of seawater. Whether shells of foraminifer taxa with differing microcrystalline structures, chemical composition, and/or preservation histories register a similar Δ18OSIMS-GSMS value is a subject of ongoing testing