A role for mast cells in geographic atrophy
FASEB JOURNAL
Authors: Ogura, Shuntaro; Baldeosingh, Rajkumar; Bhutto, Imran A.; Kambhampati, Siva P.; Scott McLeod, Donald; Edwards, Malia M.; Rais, Rana; Schubert, William; Lutty, Gerard A.
Abstract
Mast cells (MCs) are the initial responders of innate immunity and their degranulation contribute to various etiologies. While the abundance of MCs in the choroid implies their fundamental importance in the eye, little is known about the significance of MCs and their degranulation in choroid. The cause of geographic atrophy (GA), a progressive dry form of age-related macular degeneration is elusive and there is currently no therapy for this blinding disorder. Here we demonstrate in both human GA and a rat model for GA, that MC degranulation and MC-derived tryptase are central to disease progression. Retinal pigment epithelium degeneration followed by retinal and choroidal thinning, characteristic phenotypes of GA, were driven by continuous choroidal MC stimulation and activation in a slow release fashion in the rat. Genetic manipulation of MCs, pharmacological intervention targeting MC degranulation with ketotifen fumarate or inhibition of MC-derived tryptase with APC 366 prevented all of GA-like phenotypes following MC degranulation in the rat model. Our results demonstrate the fundamental role of choroidal MC involvement in GA disease etiology, and will provide new opportunities for understanding GA pathology and identifying novel therapies targeting MCs.
In vitro testing for allergic and immunologic diseases
ALLERGY AND ASTHMA PROCEEDINGS
Authors: Ochfeld, Elisa N.; Makhija, Melanie
Abstract
In vitro tests are used to assist in the diagnosis of both allergic and immunologic diseases. Unfortunately, there is no single test that is pathognomonic for most allergic diseases. The most commonly ordered in vitro test by allergists is allergen specific IgE (slgE), which is used to help diagnose IgE mediated hypersensitivity to foods, aeroallergens and venoms. Multiple assays exist, although none of these assays have been adopted as the industry standard. Epicutaneous skin test is also a fundamental test in the diagnosis of IgE mediated hypersensitivity. In addition, total IgE, basophil activation test (BAT), and serum tryptase may also be useful in elucidating allergic diseases. Immunologists rely on laboratory testing to diagnose primary immunodeficiency diseases. These tests include serum quantitative immunoglobulins, lymphocyte immunophenotyping by flow cytometry and immune cell functional testing. Furthermore, genetic testing is invaluable in the diagnosis of many primary Immunodeficiencies.