榛村 真智子

The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.

PURPOSE. To characterize corneal epithelial cells separated from limbus in vivo by transplantation of a stainless steel ring with or without creating a defect inside the ring. METHODS. A stainless steel ring (diameter, 8 mm; width, 300 mu m; depth, 250 mu m) was transplanted into rabbit corneal stroma using 10-0 nylon interrupted suture after cutting to a 250 mu m depth by corneal vacuum trephine (diameter, 8.0 mm). Epithelial cells were removed inside the ring, and re-epithelization was evaluated after 1 week. Hematoxylin staining and immunostaining against p63, Ki67, and cytokeratin 3 were performed for phenotypic analysis of corneal epithelia. A corneal epithelial defect was centrally created inside the ring (4, 5, and 6 mm diameter) after transplantation. When re-epithelization was achieved, a central epithelial defect was continuously created until cells were exhausted within the ring. The number of created defects was also analyzed to assess the potential of re-epithelialization. RESULTS. Ring-transplanted corneal stroma showed few signs of inflammation, and when epithelium was totally removed from inside the ring, complete epithelial defects were persistent for >= 1 month. Corneal sensation was significantly decreased in corneas with the ring (P < 0.05). Immunostaining demonstrated similar expression patterns for p63, Ki67, and cytokeratin3 as the controls. When rings were transplanted into the intact cornea, inside epithelia prevented epithelial defects in vivo for >= 6 months. CONCLUSIONS. Transient-amplifying cells might maintain homeostasis for >= 1 month when separated from their limbus in vivo. This model will be useful for future stem cell research or wound healing models. (Invest Ophthalmol Vis Sci. 2011;52:8132-8137) DOI:10.1167/iovs.11-7984

Purpose: To estimate the incidence of and investigate possible risk factors for postkeratoplasty atopic sclerokeratitis in keratoconus patients undergoing keratoplasty. Design: Retrospective, noncomparative, interventional case series. Participants: Two hundred forty-seven eyes with keratoconus. Methods: We reviewed the medical records of all keratoplasty cases of keratoconus between May 2000 and December 2005 at Tokyo Dental College Ichikawa General Hospital. The incidence and clinical details of cases consistent with postkeratoplasty atopic sclerokeratitis were recorded. Main Outcome Measures: Cases with acute sclerokeratitis during the early postoperative period were retrospectively evaluated. Results: A total of 247 keratoconus eyes were followed at our clinic after keratoplasty (mean follow-up, 18.5 +/- 13.0 months). Thirty-five eyes of 29 patients (14.2%) had a history of atopic dermatitis, of which 6 eyes of 5 patients (2.4%) developed post keratoplasty atopic sclerokeratitis. Mean age of postkeratoplasty atopic sclerokeratitis patients was 29 years (range, 23-39). The mean period between keratoplasty and onset of postkeratoplasty atopic sclerokeratitis was 26 days (range, 11-41). Loosening of running sutures and wound leakage were observed in 3 eyes; persistent epithelial defects in 3 eyes; and graft melting in 2 eyes, 1 of which was perforated. Preoperative atopic blepharitis and corneal neovascularization were identified as risk factors for postkeratoplasty atopic sclerokeratitis. Conclusions: Postkeratoplasty atopic sclerokeratitis is a potentially severe complication in atopic patients undergoing keratoplasty. Systemic immunosuppression may be considered in patients with active blepharitis and corneal neovascularization.

Objective: To report the incidence of dacryoadenitis as a symptom associated with Acanthamoeba keratitis. Methods: We investigated all cases of Acanthamoeba keratitis ( 20 patients and 21 eyes) diagnosed and treated at Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Japan, between May 1, 1994, and November 30, 2005. We recorded the incidence of dacryoadenitis diagnosed using clinical signs of lacrimal gland swelling and pain on pressure, computed tomography, magnetic resonance imaging, and histopathologic analysis. Results: Eight eyes ( 38%) of 8 patients had dacryoadenitis simultaneously with Acanthamoeba keratitis. Dacryoadenitis was diagnosed using histopathologic analysis and computed tomography in 1 patient, histopathologic analysis and magnetic resonance imaging in 1, magnetic resonance imaging in 2, and clinical signs alone in 4. Histopathologic examination in 2 patients revealed moderate infiltration of lymphocytes and plasma cells in the lacrimal gland compatible with dacryoadenitis. No Acanthamoeba organisms were found in the lacrimal gland. The standard protocol for Acanthamoeba keratitis was performed without particular treatment of dacryoadenitis in all patients. Lacrimal gland swelling improved after a mean of 10 weeks ( range, 4- 17 weeks) in conjunction with symptoms of keratitis; however, 1 patient ( patient 1) required levator muscle surgery and blepharoplasty for residual ptosis. Conclusion: Dacryoadenitis is a clinical finding associated with Acanthamoeba keratitis.

Nevus of the bulbar conjunctiva is a benign pigmented lesion of the ocular surface. Unless a biopsy is required for ruling out malignant melanoma, a nevus is usually excised for cosmetic reasons only. However, with large lesions involving two or more quadrants of the bulbar conjunctiva, a total resection can be difficult. In this report, we present a case of a huge nevus treated by surgical excision and amniotic membrane transplantation for reconstruction of the bulbar conjunctiva. A 54-year-old Japanese man was referred to our clinic with suspected malignant tumor of the bulbar conjunctiva in his right eye. A large and diffuse pigmented tumor with numerous small cysts was present mainly on the upper bulbar conjunctiva. Resection of the conjunctival tumor and amniotic membrane transplantation for reconstruction of the bulbar conjunctiva were performed. The histopathological diagnosis was conjunctival nevus. Epithelialization of the bulbar conjunctiva over the amniotic membrane sheet was completed 4 weeks after resection. At 44-month follow-up, there was no recurrence or any postoperative complication. Surgical resection combined with reconstruction by amniotic membrane transplantation is effective for the treatment of large conjunctival nevus.