Iron is essential for many biological processes, however, too much or too little iron can result in a wide variety of pathological consequences, depending on the organ system, tissue or cell type affected. In order to reduce pathogenesis, iron levels are tightly controlled in throughout the body by regulatory systems that control iron absorption, systemic transport and cellular uptake and storage. Altered iron levels and/or dysregulated homeostasis have been associated with several lung diseases, including chronic obstructive pulmonary disease, lung cancer, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. However, the mechanisms that underpin these associations and whether iron plays a key role in the pathogenesis of lung disease are yet to be fully elucidated. Furthermore, in order to survive and replicate, pathogenic micro-organisms have evolved strategies to source host iron, including freeing iron from cells and proteins that store and transport iron. To counter these microbial strategies, mammals have evolved immune-mediated defence mechanisms that reduce iron availability to pathogens. This interplay between iron, infection and immunity has important ramifications for the pathogenesis and management of human respiratory infections and diseases. An increased understanding of the role that iron plays in the pathogenesis of lung disease and respiratory infections may help inform novel therapeutic strategies. Here we review the clinical and experimental evidence that highlights the potential importance of iron in respiratory diseases and infections.

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson’s disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, ERG), retinal structure (optical coherence tomography, OCT) and retinal dopaminergic cell number (tyrosine hydroxylase immunohistochemistry, IHC) at two time points (21 and 45 days) post MPTP model induction. We also investigate the effect of levodopa (L-DOPA) as a proof-of-principle chronic intervention against MPTP-induced changes in the retina. We show that MPTP decreases dopaminergic amacrine cell number (9%, p < 0.05) and that a component of the ERG that involves these cells, in particular oscillatory potential (OP) peak timing, was significantly delayed at Day 45 (7–13%, p < 0.01). This functional deficit was paralleled by outer plexiform layer (OPL) thinning (p < 0.05). L-DOPA treatment ameliorated oscillatory potential deficits (7–13%, p < 0.001) in MPTP animals. Our data suggest that the MPTP toxin slows the timing of inner retinal feedback circuits related to retinal dopaminergic pathways which mirrors findings from humans with PD. It also indicates that the MPTP model causes structural thinning of the outer retinal layer on OCT imaging that is not ameliorated with L-DOPA treatment. Together, these non-invasive measures serve as effective biomarkers for PD diagnosis as well as for quantifying the effect of therapy.

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As recognised by the National Institutes of Health (NIH) Precision Medicine Initiative (PMI), microarray technology currently provides a rapid, inexpensive means of identifying large numbers of known genomic variants or gene transcripts in experimental and clinical settings. However new generation sequencing techniques are now being introduced in many clinical genetic contexts, particularly where novel mutations are involved. While these methods can be valuable for screening a restricted set of genes for known or novel mutations, implementation of whole genome sequencing in clinical practice continues to present challenges. Even very accurate high-throughput methods with small error rates can generate large numbers of false negative or false positive errors due to the high numbers of simultaneous readings. Additional validation is likely to be required for safe use of any such methods in clinical settings. Custom-designed arrays can offer advantages for screening for common, known mutations and, in this context, may currently be better suited for accredited, quality-controlled clinical genetic screening services, as illustrated by their successful application in several large-scale pre-emptive pharmacogenomics programs now underway. Excessive, inappropriate use of next-generation sequencing may waste scarce research funds and other resources. Microarrays presently remain the technology of choice in applications that require fast, cost-effective genome-wide screening of variants of known importance, particularly for large sample sizes. This commentary considers some of the applications where microarrays continue to offer advantages over next-generation sequencing technologies.