The role of tryptase and anti-type II collagen antibodies in the pathogenesis of idiopathic epiretinal membranes

Abstract

Tsunehiko Ikeda,1 Kimitoshi Nakamura,2 Hidehiro Oku,1 Seita Morishita,1 Masanori Fukumoto,1 Hiroyuki Suzuki,1 Teruyo Kida,1 Taeko Horie,1 Tetsuya Sugiyama,3 Shinji Takai4 1Department of Ophthalmology, Osaka Medical College, Takatsuki City, Osaka, Japan; 2Nakamura Eye Clinic, Nagano, Japan; 3Nakano Eye Clinic, Kyoto, Japan; 4Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan Purpose: To investigate the pathogenesis of idiopathic epiretinal membrane (ERM) from a biochemical perspective, the relationships between ERM and tryptase activity, a serine protease, and the levels of anti-type II collagen (anti-IIC) antibodies in the serum.Patients and methods: Vitreous samples for measurement of tryptase activity were obtained from 54 eyes of 54 patients who underwent a vitrectomy for vitreoretinal disease, ie, 14 eyes of 14 patients with idiopathic macular hole, 14 eyes of 14 patients with proliferative diabetic retinopathy (PDR), 13 eyes of 13 patients with ERM, and 13 eyes of 13 patients with rhegmatogenous retinal detachment (RRD). Tryptase activity was measured by spectrophotometry. Anti-IIC antibodies were measured in the serum obtained from 17 patients with ERM, eight patients who underwent cataract surgery, 12 patients with PDR, and nine patients with RRD. In these 46 patients, the anti-IIC antibodies were measured using a Human/Monkey Anti-Type I and Type II Collagen IgG Assay Kit.Results: Vitreal tryptase activity (mean ± standard deviation [SD]) in macular hole, PDR, ERM, and RRD was 0.0146±0.0053, 0.0018±0.0018, 0.0166±0.0046, and 0.0117±0.0029 mU/mg protein, respectively. Vitreal tryptase activity was significantly higher in macular hole and ERM than in PDR and RRD (P<0.05, Fisher’s protected least significant difference). The serum levels of anti-IIC immunoglobulin G (IgG) antibody (mean ± SD) in ERM, cataract surgery, PDR, and RRD were 58.222±30.986, 34.890±18.165, 55.760±26.008, and 35.453±12.769 units/mL, respectively. The serum levels of anti-IIC IgG antibody were significantly higher in ERM and PDR than in cataract surgery and RRD (P<0.05, Fisher’s protected least significant difference, two-sided).Conclusion: In the pathogenesis of ERM, increased vitreal tryptase activity may be involved in tissue fibrosis, and elevated serum anti-IIC antibodies may lead to an immune response at the vitreoretinal interface, thus resulting in membrane formation. Keywords: idiopathic epiretinal membranes, tryptase, anti-type II collagen antibodies, vitrectomy, mast cells