Rapid Assessment of Avoidable Blindness in India

BACKGROUND: Rapid assessment of avoidable blindness provides valid estimates in a short period of time to assess the magnitude and causes of avoidable blindness. The study determined magnitude and causes of avoidable blindness in India in 2007 among the 50+ population. METHODS AND FINDINGS: Sixteen randomly selected districts where blindness surveys were undertaken 7 to 10 years earlier were identified for a follow up survey. Stratified cluster sampling was used and 25 clusters (20 rural and 5 urban) were randomly picked in each district.. After a random start, 100 individuals aged 50+ were enumerated and examined sequentially in each cluster. All those with presenting vision = 50 years were enumerated, and 94.7% examined. Based on presenting vision,, 4.4% (95% Confidence Interval[CI]: 4.1,4.8) were severely visually impaired (vision<6/60 to 3/60 in the better eye) and 3.6% (95% CI: 3.3,3.9) were blind (vision<3/60 in the better eye). Prevalence of low vision (<6/18 to 6/60 in the better eye) was 16.8% (95% CI: 16.0,17.5). Prevalence of blindness and severe visual impairment (<6/60 in the better eye) was higher among rural residents (8.2%; 95% CI: 7.9,8.6) compared to urban (7.1%; 95% CI: 5.0, 9.2), among females (9.2%; 95% CI: 8.6,9.8) compared to males (6.5%; 95% CI: 6.0,7.1) and people above 70 years (20.6%; 95% CI: 19.1,22.0) compared to people aged 50-54 years (1.3%; 95% CI: 1.1,1.6). Of all blindness, 88.2% was avoidable. of which 81.9% was due to cataract and 7.1% to uncorrected refractive errors/uncorrected aphakia. CONCLUSIONS: Cataract and refractive errors are major causes of blindness and low vision and control strategies should prioritize them. Most blindness and low vision burden is avoidable

The PtdIns 3-Kinase/Akt Pathway Regulates Macrophage-Mediated ADCC against B Cell Lymphoma

Macrophages are important effectors in the clearance of antibody-coated tumor cells. However, the signaling pathways that regulate macrophage-induced ADCC are poorly defined. To understand the regulation of macrophage-mediated ADCC, we used human B cell lymphoma coated with Rituximab as the tumor target and murine macrophages primed with IFNγ as the effectors. Our data demonstrate that the PtdIns 3-kinase/Akt pathway is activated during macrophage-induced ADCC and that the inhibition of PtdIns 3-kinase results in the inhibition of macrophage-mediated cytotoxicity. Interestingly, downstream of PtdIns 3-kinase, expression of constitutively active Akt (Myr-Akt) in macrophages significantly enhanced their ability to mediate ADCC. Further analysis revealed that in this model, macrophage-mediated ADCC is dependent upon the release of nitric oxide (NO). However, the PtdIns 3-kinase/Akt pathway does not appear to regulate NO production. An examination of the role of the PtdIns 3-kinase/Akt pathway in regulating conjugate formation indicated that macrophages treated with an inhibitor of PtdIns 3-kinase fail to polarize the cytoskeleton at the synapse and show a significant reduction in the number of conjugates formed with tumor targets. Further, inhibition of PtdIns 3-kinase also reduced macrophage spreading on Rituximab-coated surfaces. On the other hand, Myr-Akt expressing macrophages displayed a significantly greater ability to form conjugates with tumor cells. Taken together, these findings illustrate that the PtdIns 3-kinase/Akt pathway plays a critical role in macrophage ADCC through its influence on conjugate formation between macrophages and antibody-coated tumor cells

Suppression by Apoptotic Cells Defines Tumor Necrosis Factor-Mediated Induction of Glomerular Mesangial Cell Apoptosis by Activated Macrophages

Activated macrophages (Mφ) isolated from inflamed glomeruli or generated by interferon-γ and lipopolysaccharide treatment in vitro induce glomerular mesangial cell apoptosis by hitherto incompletely understood mechanisms. In this report we demonstrate that nitric oxide-independent killing of co-cultured mesangial cells by interferon-γ/lipopolysaccharide-activated Mφ is suppressed by binding/ingestion of apoptotic cells and is mediated by tumor necrosis factor (TNF). Thus, soluble TNF receptor-1 significantly inhibited induction of mesangial cell apoptosis by 1) rodent Mφ in the presence of nitric oxide synthase inhibitors or 2) human Mφ, both situations in which nitric oxide release was minimal. Furthermore, murine TNF knockout Mφ were completely unable to induce mesangial cell apoptosis in the presence of nitric oxide synthase inhibitors. We conclude that TNF-restricted Mφ-directed apoptosis of glomerular mesangial cells can be down-regulated by Mφ binding/ingestion of apoptotic cells, suggesting a new mechanism for negative feedback regulation of Mφ controls on resident cell number at inflamed sites