Author Correction: Improving Stem Cell Delivery to the Trabecular Meshwork Using Magnetic Nanoparticles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Improving Stem Cell Delivery to the Trabecular Meshwork Using Magnetic Nanoparticles.

Glaucoma is a major cause of blindness and is frequently associated with elevated intraocular pressure. The trabecular meshwork (TM), the tissue that primarily regulates intraocular pressure, is known to have reduced cellularity in glaucoma. Thus, stem cells, if properly delivered to the TM, may offer a novel therapeutic option for intraocular pressure control in glaucoma patients. For this purpose, targeted delivery of stem cells to the TM is desired. Here, we used magnetic nanoparticles (Prussian blue nanocubes [PBNCs]) to label mesenchymal stem cells and to magnetically steer them to the TM following injection into the eye's anterior chamber. PBNC-labeled stem cells showed increased delivery to the TM vs. unlabeled cells after only 15-minute exposure to a magnetic field. Further, PBNC-labeled mesenchymal stem cells could be delivered to the entire circumference of the TM, which was not possible without magnetic steering. PBNCs did not affect mesenchymal stem cell viability or multipotency. We conclude that this labeling approach allows for targeted, relatively high-efficiency delivery of stem cells to the TM in clinically translatable time-scales, which are necessary steps towards regenerative medicine therapies for control of ocular hypertension in glaucoma patients.

Fall-related risk factors and osteoporosis in women with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of osteoporotic fractures. Whilst numerous studies have demonstrated low bone density in RA, few studies have examined the risk of falling, which is another major contributor to the pathogenesis of fractures (particularly hip fractures). OBJECTIVES: The aim of this study was to see if fall risk is increased in women with RA, define high-risk subgroups, and determine what proportion of women have increased risk of hip fracture due to osteoporosis and due to increased fall risk. METHODS: We performed a case-control study of older women with RA (n = 103) compared with women without RA referred for open access bone densitometry (n = 203). We measured bone density using dual-energy X-ray absorptiometry and fall risk factors (visual acuity, ability to perform standups, and heel-toe walking). RESULTS: More women with RA gave a history of a previous fall compared with controls (54 vs 44%), although this was just short of being statistically significant (difference 10%, 95% CI -2 to 22). Women with RA were more likely to have abnormal heel-toe walking and inability to perform standups compared with controls (P<0.001); however, visual acuity was similar between cases and controls. Femoral neck osteoporosis was found in 31% and increased fall risk in 68% of women with RA. Women with RA who underperformed in heel-toe walking and were unable to do standups had significantly higher ESR, Health Assessment Questionnaire score and tender joint count. RA symptoms/signs localized to the knees and ankles were more likely to be associated with the presence of fall risk factors. CONCLUSIONS: Fall-related risk factors predictive of hip fracture are common in women with RA. Fall risk needs to be considered when RA patients are being treated for osteoporosis and further work needs to be done to help reduce the risk of falling and fracture in women with RA.

A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in terminal galactose and N-acetylglucosamine.

Serum IgG from rheumatoid arthritis patients contains a decreased number of oligosaccharide structures ending in galactose and thus there is an increase in N-acetylglucosamine as the terminal sugar, compared with healthy individuals. The relationship between these two sugars varies depending on the disease examined: IgG from patients with rheumatoid arthritis, juvenile onset chronic arthritis and Crohn's disease are at one extreme, and exhibit a reciprocal galactose:N-acetylglucosamine relationship, while Sjögren's syndrome and osteoarthritis IgG are at the other extreme, exhibiting a parallel increase in the expression of both galactose and N-acetylglucosamine. These results may occur as a consequence of more than one glycosylation site which is differentially glycosylated, but more likely by changes in the level of bisecting N-acetylglucosamine.