Involvement of premacular mast cells in the pathogenesis of macular diseases

Abstract

We previously reported on the elevated intravitreal activities of tryptase and chymase in association with idiopathic epiretinal membrane (ERM) and idiopathic macular hole (MH). In this present study, we investigated the potential intraocular production of these serine proteases, and measured and compared tryptase and chymase activities in the vitreous body and serum in ERM, MH, proliferative diabetic retinopathy (PDR), and rhegmatogenous retinal detachment (RRD) patients. In addition, nuclear staining with hematoxylin and eosin (H&E) and mast-cell staining with toluidine blue were performed on samples of the vitreous core and bursa premacularis (BPM) of MH. We also performed immunostaining on the above two regions of vitreous samples for MH with anti-tryptase antibody, anti-chymase antibody, anti-podoplanin antibody, anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) antibody, and anti-fibroblast antibody. Moreover, we performed immunostaining with anti-tryptase antibody and anti-chymase antibody on ERMs collected intraoperatively. Tryptase activity in the vitreous body was significantly higher in ERM and MH than in PDR. However, no significant differences were observed in the tryptase activity in the serum among these four diseases. Chymase activity in the vitreous body was significantly higher in MH than in the other three diseases, yet chymase activity in the serum was below detection limit in any of the diseases. Nuclear staining with H&E revealed an abundance of nuclei in the BPM region, but few in the surrounding area. Mast-cell staining with toluidine blue revealed that the BPM showed metachromatic staining. In immunostaining with anti-fibroblasts antibody, anti-tryptase antibody, anti-chymase antibody, anti-podoplanin antibody, and anti-LYVE-1 antibody, the BPM stained more strongly than the vitreous core. Tryptase and chymase-positive cells were also observed in ERM. These findings revealed that the presence of mast cells in the BPM potentially represent the source of these serine proteases. Moreover, the BPM, as a lymphatic tissue, may play an important role in the pathogenesis of macular disease.

Spontaneous disappearance and recurrence of impending macular hole: a case report

“…It should be noted that it is difficult to attribute the improvement in VA and the restoration of the lamella structure of the fovea centralis simply to glial cell proliferation. In previous studies, we speculated the presence of neural stem cell-like cells with regenerative ability in the fovea centralis [15, 16], and reported the possible involvement of serine proteases such as chymase and tryptase in the vitreous body in the development of MH and ERM [17–19]. Since chymase has an apoptotic effect and tryptase induces tissue fibrosis, we theorized that such serine proteases might be involved in the pathogenesis of MH and ERM.…”

Expression of Lymphatic Markers in the Berger’s Space and Bursa Premacularis

“…Although the BPM has been regarded as an empty space, as mentioned above [ 27 ], our recent immunostaining study showed that the BPM might be a parenchymal tissue containing numerous cells expressing lymphatic endothelial cell markers podoplanin and LYVE-1; mast cell markers tryptase and chymase; and ER-TR7, a reticular fibroblast marker antibody [ 9 ]. Podoplanin and LYVE-1 are also implicated in uveal melanoma [ 53 ].…”

“…Our recent study exhibited that the vitrectomy specimens of the thin tissue remaining on the macula after induction of posterior vitreous detachment (PVD) contained numerous cells, including those expressing lymphatic markers, such as podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) [ 9 ]. This thin tissue has generally been considered the remaining vitreous cortex.…”

“…This thin tissue has generally been considered the remaining vitreous cortex. However, our findings indicated the possibility that it was the BPM and that it that might have properties similar to lymph nodes [ 9 ].…”

Involvement of Anoikis in Dissociated Optic Nerve Fiber Layer Appearance

“…We previously reported that the intravitreal activities of chymase and tryptase, which are serine proteases produced by mast cells, were increased in idiopathic MH and idiopathic ERM patients [ 86 ]. Based on the findings of our histological study, we also identified that mast cells residing in the bursa premacularis, a peculiar sac-like structure present in the premacular vitreous, might be the source of these serine proteases [ 87 ]. Mast cells are immune cells of the myeloid lineage that are present in mucosal and connective tissues throughout the body [ 88 ].…”