Fibronectin has multifunctional roles in posterior capsular opacification (PCO).

Fibrotic posterior capsular opacification (PCO), one of the major complications of cataract surgery, occurs when lens epithelial cells (LCs) left behind post cataract surgery (PCS) undergo epithelial to mesenchymal transition, migrate into the optical axis and produce opaque scar tissue. LCs left behind PCS robustly produce fibronectin, although its roles in fibrotic PCO are not known. In order to determine the function of fibronectin in PCO pathogenesis, we created mice lacking the fibronectin gene (FN conditional knock out -FNcKO) from the lens. While animals from this line have normal lenses, upon lens fiber cell removal which models cataract surgery, FNcKO LCs exhibit a greatly attenuated fibrotic response from 3 days PCS onward as assessed by a reduction in surgery-induced cell proliferation, and fibrotic extracellular matrix (ECM) production and deposition. This is correlated with less upregulation of Transforming Growth Factor ß (TGFß) and integrin signaling in FNcKO LCs PCS concomitant with sustained Bone Morphogenetic Protein (BMP) signaling and elevation of the epithelial cell marker E cadherin. Although the initial fibrotic response of FNcKO LCs was qualitatively normal at 48 h PCS as measured by the upregulation of fibrotic marker protein αSMA, RNA sequencing revealed that the fibrotic response was already quantitatively attenuated at this time, as measured by the upregulation of mRNAs encoding molecules that control, and are controlled by, TGFß signaling, including many known markers of fibrosis. Most notably, gremlin-1, a known regulator of TGFß superfamily signaling, was upregulated sharply in WT LCs PCS, while this response was attenuated in FNcKO LCs. As exogenous administration of either active TGFß1 or gremlin-1 to FNcKO lens capsular bags rescued the attenuated fibrotic response of fibronectin null LCs PCS including the loss of SMAD2/3 phosphorylation, this suggests that fibronectin plays multifunctional roles in fibrotic PCO development.

Performance and longevity of a novel intraosseous device in a goat (Capra hircus) model.

We performed 2 studies to assess the function and longevity of a novel intraosseous catheter device. For study 1, 9 goats were assigned to 3 groups (intraosseous catheter in the proximal humerus, intraosseous catheter in the proximal tibia, or standard jugular catheter). Devices in the tibia remained in place for less time than did those in the humerus, and no goats exhibited radiographic evidence of resulting damage or structural change in surrounding bone. Positive bacterial cultures were found in all 9 goats at various time points. In study 2, 18 goats were assigned to 2 groups (intraosseous catheter in the wing of the ilium or proximal humerus). Samples for serial aerobic and anaerobic blood cultures and CBC were collected while devices remained in use. Clinical monitoring and removal criteria were identical those for study 1. Catheters in the ilium remained in place for less than 24 h on average, and those in the humerus remained in place for an average of 2.5 d. Several goats with proximal humeral catheters demonstrated moderate lameness after removal, and radiographic evidence of periosteal bone growth was noted in another goat. Bloodwork indicated mild elevations of WBC counts from baseline in some cases. Bacterial growth was found in samples from 4 of 18 goats at various time points. Our study indicated that intraosseous catheters may remain safely in place for more than 24 h, but animals should be monitored closely for negative side effects for several days after removal.