Dynamic regulation of the mitochondrial network by mitofusins (MFNs) modulates energy production, cell survival, and many intracellular signaling events including calcium handling. However, the relative importance of specific mitochondrial functions and their dependence on MFNs vary greatly among cell types. Osteoclasts have many mitochondria, and increased mitochondrial biogenesis and oxidative phosphorylation enhance bone resorption, but little is known about the mitochondrial network or MFNs in osteoclasts. Because expression of each MFN isoform increases with osteoclastogenesis, we conditionally deleted both MFN1 and -2 (dcKO) in murine osteoclast precursors, finding that this increased bone mass in young female mice, and abolished osteoclast precursor differentiation into mature osteoclasts, in vitro. Defective osteoclastogenesis was reversed by overexpression of MFN2 but not MFN1; therefore we generated mice lacking only MFN2 in osteoclasts. MFN2-deficient female mice had increased bone mass at 1 year and resistance to RANKL-induced osteolysis at 8 weeks. To explore whether MFN-mediated tethering or mitophagy is important for osteoclastogenesis, we overexpressed MFN2 variants defective in either function in MFN1/2 dcKO precursors and found that although mitophagy was dispensable for differentiation, tethering was required. Since the master osteoclastogenic transcriptional regulator nuclear factor of activated T cells 1 (NFATC1) is calcium-regulated, we assessed calcium release from the endoplasmic reticulum (ER) and store-operated calcium entry and found that the latter was blunted in dcKO cells. Restored osteoclast differentiation by expression of intact MFN2 or the mitophagy-defective variant was associated with normalization of store-operated calcium entry and Nfatc1 levels, indicating that MFN2 controls mitochondria-ER tethering in osteoclasts.
Conjunctival fibrosis remains the major impediment to the success of glaucoma filtration surgery. Anti-metabolites remain the gold standard for mitigating post-surgical fibrosis, but they are associated with high complication rates and surgical failure rates. Establishing a more targeted approach to attenuate conjunctival fibrosis may revolutionize the surgical approach to glaucoma. A new strategy is needed to prevent progressive tissue remodeling and formation of a fibrotic scar, subsequently increasing surgical success and reducing the prevalence of glaucoma-related vision loss. Advancements in our understanding of molecular signaling and biomechanical cues in the conjunctival tissue architecture are broadening the horizon for new therapies and biomaterials for the mitigation of fibrosis. This review aims to highlight the strategies and current state of promising future approaches for targeting fibrosis in glaucoma filtration surgery.
Bone infections, also known as infectious osteomyelitis, are accompanied by significant inflammation, osteolysis, and necrosis. Osteoclasts (OCs) are the bone-resorbing cells that work in concert with osteoblasts and osteocytes to properly maintain skeletal health and are well known to respond to inflammation by increasing their resorptive activity. OCs have typically been viewed merely as effectors of pathologic bone resorption, but recent evidence suggests they may play an active role in the progression of infections through direct effects on pathogens and via the immune system. This review discusses the host- and pathogen-derived factors involved in the in generation of OCs during infection, the crosstalk between OCs and immune cells, and the role of OC lineage cells in the growth and survival of pathogens, and highlights unanswered questions in the field.
27 June 2019 in Journal of Bone and Mineral Research
Strabismus surgery follow-up is used to identify postoperative complications and assess surgical outcomes. Traditionally, follow-ups at our center required in-person postoperative week 1 (POW1) visits. Common obstacles to completing clinic visits include work conflicts and transportation challenges. The purpose of this study was to investigate the safety, cost-effectiveness, and potential for improving healthcare access of phone call follow-ups instead of in-person follow-ups at POW1. We retrospectively reviewed data from 370 consecutive strabismus surgery patients between mid-2018 and 2021. Successful POW1 follow-up was defined as an attended in-person visit or completion of a standardized phone questionnaire. Of 188 scheduled in-person POW1 visits, 179 were successful. Of the 182 scheduled phone POW1 follow-ups, 175 were successful (95.2 vs 96.2% successes [P = 0.66]). Of 148 POW1 in-person visits with another follow-up within 6 months, 9 complications were identified. Of 150 POW1 phone follow-ups with another follow-up within 6 months, 7 complications were identified. There were no missed complications noted at postoperative month 3. No complications resulted in vision loss. The phone follow-up group traveled an average distance of 70.0 miles; the in-person group, 45.9 miles. Overall, 44.1% of patients had to travel >50 miles for their postoperative visits. In our study cohort, POW1 phone call follow-ups after strabismus surgery maintained patient engagement and had equivalent rates of complication detection to in-person follow-up. Implementing phone calls for early follow-up has the potential to improve healthcare accessibility for patients who travel long distances.
Introduction Despite the rise of micro-invasive glaucoma surgery (MIGS), glaucoma drainage device implantation continues to be a mainstay among glaucoma surgical treatment options. Anterior chamber tube placement, while effective in reducing intraocular pressure (IOP), poses corneal endothelial risks. Ciliary sulcus tube placement shows promise in reduced corneal endothelial cell loss, but proper sulcus placement can be challenging. Our study describes the initial safety and effectiveness results using a novel sulcus tube internal needle guidewire (STING) technique for glaucoma drainage device insertion into the ciliary sulcus. Methods We retrospectively reviewed the charts of all consecutive patients who underwent the STING technique using the Ahmed ClearPath, Ahmed Glaucoma Valve, or Baerveldt glaucoma implant with at least 6 months of follow-up. Demographic characteristics, type of glaucoma, previous medical and surgical treatment, pre- and postoperative IOP, pre- and postoperative medications, complications, and success rates were recorded. Results Out of nine eyes, seven resulted in qualified success (77.8%). Preoperative mean IOP was 23.8 ± 6.3 mmHg, and postoperative IOP decreased significantly to 14.9 ± 3.7 mmHg (p = 0.008). The average number of preoperative medications per patient was 4.4 ± 0.7, while the average number of postoperative medications per patient was reduced significantly to 3.6 ± 1.0 (p = 0.039). Conclusion The STING technique is a novel method for placing a glaucoma drainage device into the ciliary sulcus, leading to IOP lowering with minimal complications. The STING technique is designed to improve surgical ease and increase anatomical precision of sulcus tube placement. Video available for this article.