Anti-ANXA1 monoclonal antibody, clone 4B9

Purpose: The purpose of this study was to examine the expression of the antiinflammatory protein Annexin Al (AnxA1) in mice and human retinae during uveitis and to determine whether local administration of human recombinant AnxAl (hrAnxAl) can suppress uveitis in mice. Methods: Retinal sections from mice (healthy normal and uveitis) and postmortem human (no history of eye disease (n = 5) and uveitis (n = 7)) were stained for AnxA1 expression and imaged by immunofluorescence microscopy. AnxA1 cellular expression was determined by colabeling with CD45, glial fibrillary acidic protein (GFAP), and Iba-1 cells, with additional staining of AnxA1 receptors formyl peptide receptor 1 (FPRI) and FPRL1/FPR2. Mice with acute endotoxin-induced uveitis and chronic experimental autoimmune uveitis were treated locally by intravitreal injection with hrAnxA1, and disease was assessed by clinical scoring and quantification of leukocyte infiltrate via flow cytometry. Results: Constitutive expression of AnxAl was observed in both healthy mouse and human retinae, and its expression increased during uveitis compared to healthy controls. AnxAl colocalizes predominantly with CD45(+) cells, GFAP(+) macroglia, and to a lesser extent, Iba-1(+) myeloid cells. We also demonstrate that local treatment with hrAnxA1 attenuates the severity of uveitis in mice. Conclusions: These data indicate that locally expressed AnxA1 is elevated in the retina during intraocular inflammation. We demonstrate that local administration of hrAnxA1 to augment levels results in suppression of uveitis in mice. Translational Relevance: Our data suggest that elevated expression of retinal AnxAl in human uveitis may be immunoregulatory and that local supplementation with hrAnxA1 may provide a potential novel treatment for inflammatory eye diseases such as noninfectious uveitis.

People in the Solomon Islands today are considered to have derived from Asian- and Papuan-related ancestors. Papuan-related ancestors colonized Near Oceania about 47,000 years ago, and Asian-related ancestors were Austronesian (AN)-speaking population, called Lapita, who migrated from Southeast Asia about 3,500 years ago. These two ancestral populations admixed in Near Oceania before the expansion of Lapita people into Remote Oceania. To understand the impact of the admixture on the adaptation of AN-speaking Melanesians in Near Oceania, we performed the genome-wide single nucleotide polymorphism (SNP) analysis of 21 individuals from Munda, the main town of the New Georgia Islands in the western Solomon Islands. Population samples from Munda were genetically similar to other Solomon Island population samples. The analysis of genetic contribution from the two different ancestries to the Munda genome revealed significantly higher proportions of Asian- and Papuan-related ancestries in the region containing the annexin A1 (ANXA1) gene (Asian component > 82.6%) and in the human leukocyte antigen (HLA) class II region (Papuan component > 85.4%), respectively. These regions were suspected to have undergone natural selection since the time of admixture. Our results suggest that admixture had affected adaptation of AN-speaking Melanesians in the Solomon Islands.