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.

Highlights

  • Idiopathic epiretinal membrane (ERM) and idiopathic macular hole (MH) are known to cause metamorphopsia and reduced visual acuity, and occur mainly in middle-aged and older adults

  • It has been proposed that the causes of ERM include a mechanism of vitreous traction on the macula that initiates cell proliferation or extracellular matrix accumulation on the posterior wall of the posterior precortical vitreous pocket (PPVP) [2], an anatomical structure previously termed ’bursa premacularis’ (BPM) by Worst in 1977 [3], and that vitreomacular traction is generally accepted as a cause of MH [4]

  • Nuclear staining with hematoxylin and eosin (H&E) revealed an abundance of nuclei in the BPM region, yet few in the surrounding area (Fig 4A and 4B)

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Summary

Introduction

Idiopathic epiretinal membrane (ERM) and idiopathic macular hole (MH) are known to cause metamorphopsia and reduced visual acuity, and occur mainly in middle-aged and older adults. It has been proposed that the causes of ERM include a mechanism of vitreous traction on the macula that initiates cell proliferation or extracellular matrix accumulation on the posterior wall of the posterior precortical vitreous pocket (PPVP) [2], an anatomical structure previously termed ’bursa premacularis’ (BPM) by Worst in 1977 [3], and that vitreomacular traction is generally accepted as a cause of MH [4]. It has been considered that the PPVP and the BPM are arguably the same space. Besides the thin membrane remaining on the retina after artificial posterior vitreous detachment has been regarded as the posterior wall of PPVP. Fine and Spaide, as well as Sato et al, reportedly observed a similar phenomena [6, 7].Recently, several studies have investigated the morphology of ERM and MH using optical coherence tomography (OCT) [8, 9], few studies have been conducted to investigate biochemical features of these macular diseases

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