Local synthesis of hepcidin in the anterior segment of the eye: A novel observation with physiological and pathological implications

TGFβ2-Hepcidin Feed-Forward Loop in the Trabecular Meshwork Implicates Iron in Glaucomatous Pathology

“…Local expression of hepcidin and Fpn in the TM reinforce similar observations in a recent report, 15 and suggest stringent regulation of iron at this site by its autocrine and paracrine activity. 11,12,48,49 However, upregulation of hepcidin by TGF-β2 through Smad4, a potent transcriptional activator of hepcidin, 10 is likely to increase intracellular iron and the potential for iron-catalyzed ROS.…”

“…Protein lysates were fractionated by SDS-PAGE and analyzed by Western blotting as described. 15,16,33,37 Proteins of interest were visualized by probing with specific antibodies (antibody list in Supplementary Table S2). RT-PCR was carried out as described earlier 15 (primer list in Supplementary Table S3).…”

“…13 In the eye, hepcidin is synthesized locally in the neuroretina and ciliary epithelium, suggesting local regulation of iron transport to the neuroretina and the AH respectively. [14][15][16] Expression of hepcidin in the corneal endothelium, lens epithelium, and TM indicate additional regulation of iron exchange between these structures and the AH. 15 Although helpful in maintaining stringent regulation of iron, hepcidin is upregulated by inflammatory cytokines as well, [17][18][19] and is likely to create a poten-tially toxic microenvironment by increasing intracellular iron and iron-catalyzed reactive oxygen species (ROS).…”

“… 14 – 16 Expression of hepcidin in the corneal endothelium, lens epithelium, and TM indicate additional regulation of iron exchange between these structures and the AH. 15 Although helpful in maintaining stringent regulation of iron, hepcidin is upregulated by inflammatory cytokines as well, 17 – 19 and is likely to create a potentially toxic microenvironment by increasing intracellular iron and iron-catalyzed reactive oxygen species (ROS). 20 In this respect, it is notable that TM cells respond to mechanical stress by upregulating TGF-β1 and IL-6, 21 cytokines known to upregulate hepcidin, 17 , 22 , 23 and the limited but noticeable protection of retinal ganglion cells by iron chelators suggests a prominent role of iron in the pathogenesis of POAG.…”

Retinal Degeneration and Alzheimer’s Disease: An Evolving Link

“…In the brain, hepcidin is expressed in the cortex, hippocampus, cerebellum, thalamus, and medulla oblongata [ 108 , 109 , 110 ]. In the eye, the synthesis and expression of hepcidin is noted in several cell types in the retina and the anterior segment [ 111 , 112 , 113 ].…”