Tantri Lestari, Nobuyo Yawata, Gabriel Gonzalez, Hiroko Miyadera, Daisuke Motooka, Yuko Imamura, Hiroya Oki, Yasuo Mori, Mariko Shirane, Seik-Soon Khor, Yosuke Omae, Mihoko Shimada, Ayu Dyah Windy, Satoko Nakano, Hiroki Tsutsui, Shiori Kuramoto, Chihiro Fukui, Riku Nakamura, Satoshi Yamana, Toshikatsu Kaburaki, Hisashi Mashimo, Hiroshi Takase, Ryoji Yanai, Eiichi Hasegawa, Kensuke Shibata, Makoto Yawata, Katsushi Tokunaga, Nobuyuki Ohguro and Koh-Hei Sonoda : Molecular Variations in Glycoprotein B of Asian Human Cytomegalovirus: Potential Impact on Virus Entry and Immune Evasion in Ocular Diseases., Journal of Medical Virology, 98, 1, 2026.
(要約)
Human cytomegalovirus (HCMV)-associated ocular diseases have gained increasing attention due to a recent rise in cases diagnosed in Asia. A glycoprotein encoded by the virus UL55 gene, glycoprotein B (gB), is essential for viral entry and a primary target for naturally-produced antibodies and vaccine development. gB is classified into five genotypes (gB1-gB5) based on polymorphisms surrounding the furin cleavage site. This study analyzed the UL55 gene in 62 blood and ocular specimens of Japanese patients with CMV viremia and CMV-associated ocular diseases. Distinct gB genotype distributions were found between sample types (p = 0.008): gB2 was the most prevalent genotype in blood samples (41%, 11/27), while gB3 (43%, 15/35) and gB1 (37%, 13/35) predominated in ocular fluids. Viral loads were significantly higher in gB1 and gB3-positive samples compared with gB2 (p = 0.016). A shared gB1/gB3-specific peptide (aa 190-204; SRVIAGTVFVAYHRD), distinct from that of gB2, exhibited reduced HLA class II binding. In addition, a K518R substitution was identified in 80% of gB1 and gB3 variants in our cohort and other Asian-derived GenBank entries, but only 3% of European origin strains. This substitution was significantly enriched in ocular fluids from patients with CMV ocular infection (71%, 17/24), compared with blood from patients with CMV viremia (32%, 8/25) (p = 0.01). The predicted structural modeling infers that this substitution is located in the core of gB Domain III, and potentially increase the local molecular stability in this region. Evolutionary analyses indicated positive selective pressure at this site, implying the biological significance. These findings infer that genetic variations enriched in ocular fluids and Asian-derived HCMV strains, may contribute to ocular pathogenesis through influencing on viral entry and reduced immune recognition.
Hirotaka Kondo, Mariko Egawa, Ryoji Yanai and Yoshinori Mitamura : Bilateral Cytomegalovirus Retinitis With Co-infection of Epstein-Barr Virus and Varicella-Zoster Virus: A Rare Case., Curēus, 17, 12, 2025.
(要約)
Cytomegalovirus retinitis (CMVR) is a form of infectious uveitis, a disease characterized by inflammation of the uvea, the middle layer of the eye. It is caused by the cytomegalovirus (CMV). Although CMVR generally involves a single virus, rare cases have been reported in which multiple viral DNAs have been detected in intraocular fluid using polymerase chain reaction (PCR) testing. The present case report documents a rare case of bilateral infectious uveitis with simultaneous detection of CMV and Epstein-Barr virus (EBV) in the right eye and CMV and varicella-zoster virus (VZV) in the left eye. A 75-year-old female patient with a history of long-term immunosuppressive therapy for rheumatoid arthritis presented with bilateral mild iritis and worsening retinal inflammation in the left eye. Fundus examination revealed granular exudates and retinal vascular occlusion in both eyes, with circumferential retinal lesions in the left eye. Qualitative PCR testing of the aqueous humor identified CMV and EBV in the right eye and CMV and VZV in the left eye. The patient was treated with intravenous acyclovir and ganciclovir, followed by intravitreal ganciclovir injections. Despite stabilization of the right eye, the left eye showed rapid lesion progression and developed a rhegmatogenous retinal detachment requiring surgical intervention. At the final follow-up, the corrected decimal visual acuity was 0.7 in the right eye and 0.02 in the left eye.Co-infection with multiple herpes viruses in viral retinitis is extremely rare. Immunosuppression may predispose individuals to such infections. PCR testing of intraocular fluid has been instrumental in diagnosis and guiding treatment. However, comprehensive evaluation is required to determine the pathogenicity of the viruses detected. This case highlights the importance of PCR testing for accurate diagnosis of atypical infectious uveitis. Although rare, concurrent infections with multiple herpesviruses may occur, and coinfection with VZV in particular could be associated with a poorer prognosis.
Ryoji Yanai, Hei Sho Uchi, Yukiko Kondo, Youichiro Fujitsu, Katsuyoshi Suzuki, Keiko Yoshimura, Naoki Kumagai, Mariko Egawa and Yoshinori Mitamura : The epidemiology of uveitis: comparison of its causes and visual outcomes between three-tiered medical facilities in Ube city, Scientific Reports, 15, 1, 8998, 2025.
(要約)
This study aimed to conduct a comparative epidemiological survey of uveitis across various healthcare settings and elucidate the clinical characteristics. We conducted a retrospective cross-sectional study in the Ube-City medical region in Yamaguchi prefecture and recruited 268 patients from a university hospital (151 patients), municipal hospitals (51 patients), and private eye clinics (58 patients). Medical records of patients newly diagnosed with uveitis between January 2018 and December 2019 in the institutes were included, reviewed, and compared. The main outcomes included the number of uveitis causes, treatment methods, and visual acuity. Panuveitis, which is associated with systemic diseases, such as Vogt-Koyanagi-Harada disease and sarcoidosis, was more prominent in university hospital patients. Conversely, anterior uveitis, including traumatic iritis, was prominently detected in general hospitals and private eye clinics. The best-corrected visual acuity improved to 1.0 (logMAR = 0); an improvement of 74%, 61%, and 54% was observed in private eye clinic, general hospital, and university hospital patients, respectively. This study identified differences in uveitis presentation and treatment across diverse clinical settings. The results of this study provide valuable data for differentiating the causes of uveitis at university hospitals, general hospitals, and private eye clinics.
(キーワード)
Community hospitals / Panuveitis / University hospital / Uveitis / Visual impairment
Ryoji Yanai, Sora Mizukami, Akihiko Sakamoto, Kenji Takemoto, Tetsuya Seto, Kazuya Uehara, Kiminori Yukata, Takashi Sakai, Keiko Iwaisako, Norihiko Takeda, Ryoji Yanai and Masataka Asagiri : Cell cycle checkpoint factor p15Ink4b is a novel regulator of osteoclast differentiation., Scientific Reports, 15, 1, 2025.
(要約)
Osteoclasts are specialized cells essential for bone resorption, a crucial process in bone remodeling, and dysregulation of osteoclastogenesis can lead to pathological bone loss such as osteoporosis and rheumatoid arthritis. Therefore, understanding the precise mechanisms governing osteoclast differentiation is crucial for developing effective therapies for skeletal diseases. In osteoclastogenesis, as well as other differentiated cells, it is well understood that cell cycle arrest is essential for terminal differentiation and is tightly regulated by CDK inhibitors such as Cip/Kip family and Ink4 family protein. In this manuscript, we identified p15Ink4b, a member of the Ink4 family, as a novel regulator of osteoclastogenesis by comprehensive single-cell RNA sequence data reanalyzing. Furthermore, histological analysis and in vitro osteoclast differentiation assay revealed that p15Ink4b functionally regulates osteoclastogenesis. Our findings may not only provide insights into the molecular mechanisms of osteoclast differentiation but also underscore the potential of harnessing cell cycle mechanisms to develop novel therapeutic strategies for bone diseases.
Tetsuya Seto, Kiminori Yukata, Shunya Tsuji, Yusuke Takeshima, Takeshi Honda, Akihiko Sakamoto, Kenji Takemoto, Hiroki Sakai, Mayu Matsuo, Yurika Sasaki, Mizuki Kaneda, Mikako Yoshimura, Atsushi Mihara, Kazuya Uehara, Aira Matsugaki, Takayoshi Nakano, Koji Harada, Yoshiro Tahara, Keiko Iwaisako, Ryoji Yanai, Norihiko Takeda, Takashi Sakai and Masataka Asagiri : Methylglyoxal compromises callus mineralization and impairs fracture healing through suppression of osteoblast terminal differentiation., Biochemical and Biophysical Research Communications, 747, 2025.
(要約)
Impaired fracture healing in diabetic patients leads to prolonged morbidity and increased healthcare costs. Methylglyoxal (MG), a reactive metabolite elevated in diabetes, is implicated in various complications, but its direct impact on bone healing remains unclear. Here, using a non-diabetic murine tibial fracture model, we demonstrate that MG directly impairs fracture healing. Micro-computed tomography revealed decreased volumetric bone mineral density in the callus, while callus volume remained unchanged, resulting in a brittle bone structure. This was accompanied by reduced expression of osteocalcin and bone sialoprotein, both critical for mineralization. Biomechanical analysis indicated that MG reduced the mechanical resilience of the fracture site without altering its elastic strength, suggesting that the impairment was not primarily due to the accumulation of advanced glycation end-products in the bone extracellular matrix. In vitro studies confirmed that non-cytotoxic concentrations of MG inhibited osteoblast maturation and mineralization. Transcriptomic analysis identified downregulation of Osterix, a key transcription factor for osteoblast maturation, without altering Runx2 levels, leading to decreased expression of key mineralization-related factors like osteocalcin. These findings align with clinical observations of reduced circulating osteocalcin levels in diabetic patients, suggesting that the detrimental effects of MG on osteoblasts may extend beyond bone metabolism. Our study highlights MG and MG-sensitive pathways as potential therapeutic targets for improving bone repair in individuals with diabetes and other conditions characterized by elevated MG levels.
Ryoji Yanai and Yoshinori Mitamura : The influence of thick-type conventional soft contact lenses YOUSOFT ®, developing for the astigmatism correction on a rabbit corneal epithelium, ARVO2025, Apr. 2025.
2.
Ryoji Yanai, 三﨑 裕子, Mariko Egawa, Masayuki Yamada and Yoshinori Mitamura : Two cases of Tatto-associated granulomatous uveitis, INFLAMMATIO 2024, Nov. 2024.
3.
Ryoji Yanai and Yoshinori Mitamura : The effects of the thick type of YOUSOFT contact lenses for aphakic hyperopia on a rabbit corneal epithelium, ISCLR Symposium, Aug. 2024.
Fumiko Murao, Ryoji Yanai and Yoshinori Mitamura : Retina Structural Changes After Treatment With Faricimab fou DME:J-CREST, 第64回日本網膜硝子体学会総会, Dec. 2025.