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Article ; Online: The existence of senescent cells in conjunctival epithelium from elderly individuals.

Tomioka, Yasufumi / Kitazawa, Koji / Numa, Kohsaku / Hughes, Jun-Wei B / Yokoi, Norihiko / Sotozono, Chie

2024 Volume 68, Issue 2, Page(s) 157–165

Abstract: Purpose: The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16: Study design: Clinical and experimental.: Methods: Healthy ... ...

Abstract	Purpose: The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16 Study design: Clinical and experimental. Methods: Healthy conjunctival tissue samples were obtained from middle-aged and elderly subjects. RT-qPCR was performed to assess the expression of senescence markers CDKN2A (p16 Results: Our study involved 19 conjunctival tissue samples (10 elderly and 9 middle-aged), mean age [elderly: 75.8 ± 3.7 years (72-81), middle-aged: 52.7 ± 7 years (38-59)], sex (elderly: 3 men, 7 women; middle-aged: 3 men, 6 women). The expression of p16 Conclusions: Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.
MeSH term(s)	Aged ; Middle Aged ; Male ; Humans ; Female ; Aged, 80 and over ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor p16/analysis ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Ki-67 Antigen ; Aging ; Cellular Senescence ; Epithelium/chemistry ; Epithelium/metabolism
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; Ki-67 Antigen
Language	English
Publishing date	2024-02-05
Publishing country	Japan
Document type	Journal Article
ZDB-ID	82032-5
ISSN	1613-2246 ; 0021-5155
ISSN (online)	1613-2246
ISSN	0021-5155
DOI	10.1007/s10384-023-01047-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A case of lattice corneal dystrophy type 1 with bilateral Mooren's ulcer.

Kayukawa, Kanae / Kitazawa, Koji / Wakimasu, Koichi / Sotozono, Chie / Kinoshita, Shigeru

American journal of ophthalmology case reports

2023 Volume 29, Page(s) 101796

Abstract: Purpose: To report a rare case of lattice corneal dystrophy type 1 (LCD1) with bilateral Mooren's ulcer.: Observations: This case involved a 62-year-old male patient with LCD1 who presented with the primary complaint of experiencing pain and ... ...

Abstract	Purpose: To report a rare case of lattice corneal dystrophy type 1 (LCD1) with bilateral Mooren's ulcer. Observations: This case involved a 62-year-old male patient with LCD1 who presented with the primary complaint of experiencing pain and photophobia in both eyes for 2 months prior to his initial visit. Upon examination, a peripheral corneal ulcer was observed in both eyes covering more than 3 of the 4 quadrants, accompanied with ciliary injection and severe corneal infiltration. He was diagnosed with Mooren's ulcer, and treatment with 0.1% betamethasone and 0.5% levofloxacin eye drops and systemic cyclosporine and betamethasone was initiated. At 1-month post treatment initiation, a remaining ulceration ridge was observed on the corneal surface in his left eye, which was subsequently resected. Complete epithelialization was achieved at 1-month postoperative in the left eye and after 6-months of conservative topical treatment in the right eye. At 8-9 years post onset of Mooren's ulcer, the patient underwent penetrating keratoplasty in both eyes while undergoing treatment with oral cyclosporine administration for severe corneal opacity due to progression of lattice dystrophy. Post treatment, there has been no recurrence of ulcerations, even though more that 10 years has passed since the onset of Mooren's ulcer. Conclusions and importance: To the best of our knowledge, this is the first reported case of LCD1 with bilateral Mooren's ulcer, and in this rare case, the patient was successfully treated with a combination of steroid, cyclosporine, and peripheral superficial keratectomy, and a good visual outcome was achieved after penetrating keratoplasty (PK) under the use of systemic cyclosporine.
Language	English
Publishing date	2023-01-12
Publishing country	United States
Document type	Case Reports
ISSN	2451-9936
ISSN (online)	2451-9936
DOI	10.1016/j.ajoc.2023.101796
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Current Advancements in Corneal Cell-Based Therapy.

Kitazawa, Koji / Sotozono, Chie / Kinoshita, Shigeru

Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)

2022 Volume 11, Issue 4, Page(s) 335–345

Abstract: Corneal epithelial stem cells (CEpSCs) mostly reside at the limbal area and are responsible for tissue homeostasis throughout life. Once complete CEpSC deficiency occurs, regenerative medicine cell-based therapy using CEpSCs or their alternatives can ... ...

Abstract	Corneal epithelial stem cells (CEpSCs) mostly reside at the limbal area and are responsible for tissue homeostasis throughout life. Once complete CEpSC deficiency occurs, regenerative medicine cell-based therapy using CEpSCs or their alternatives can provide successful clinical outcomes. Due to an improved understanding of CEpSCs and mucosal epithelial stem cells, major advancements have been made over the past few decades in in vivo and ex vivo cell-based ocular surface reconstruction therapies for the treatment of severe ocular surface diseases. New therapeutic concepts and clinical strategies are emerging for the treatment of corneal endothelial dysfunction. For example, unlike corneal epithelial cells, in vivo corneal endothelial cells (CECs) stop proliferating and are arrested in the G1 phase of the cell cycle due to cell-to-cell contact inhibition and exposure to a high concentration of transforming growth factor-beta in the aqueous humor. Thus, the production of CECs with good functionality in culture has consistently been difficult. To solve this problem, Rho-associated protein kinase inhibition has taken center stage, as it not only makes the production of human CECs in culture closely mimic the functional characteristics of in vivo healthy CECs possible but also helps sustain those biological properties. Thus, cultured human CEC injection therapy is now moving to the forefront for the treatment of corneal endothelial failure. Herein, we summarize key historical discoveries in corneal cell-based regenerative medicine and illustrate the concept of corneal cell therapy for the treatment of refractory corneal epithelial and endothelial diseases.
MeSH term(s)	Cell- and Tissue-Based Therapy ; Cells, Cultured ; Cornea ; Corneal Diseases/therapy ; Endothelial Cells ; Endothelium, Corneal ; Humans ; Stem Cells/metabolism
Language	English
Publishing date	2022-08-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2756329-7
ISSN	2162-0989 ; 2162-0989
ISSN (online)	2162-0989
ISSN	2162-0989
DOI	10.1097/APO.0000000000000530
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Article: Current Evidence for

Aoki, Takanori / Kitazawa, Koji / Deguchi, Hideto / Sotozono, Chie

Microorganisms

2021 Volume 9, Issue 2

Abstract: ... ...

Abstract	Corynebacterium
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9020254
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Article ; Online: Donor Corneal Endothelial Cell Maturity and Its Impact on Graft Survival in Glaucoma Patients Undergoing Corneal Transplantation.

Kitazawa, Koji / Toda, Munetoyo / Ueno, Morio / Wakimasu, Koichi / Tomioka, Yasufumi / Uehara, Asako / Sotozono, Chie / Kinoshita, Shigeru

American journal of ophthalmology

2024 Volume 262, Page(s) 1–9

Abstract: Purpose: To examine corneal graft survival via corneal endothelial cell density (ECD) and corneal endothelial cell loss (ECL) at 5 years post-transplantation in the eyes of patients with and without a history of undergoing glaucoma surgery according to ... ...

Abstract	Purpose: To examine corneal graft survival via corneal endothelial cell density (ECD) and corneal endothelial cell loss (ECL) at 5 years post-transplantation in the eyes of patients with and without a history of undergoing glaucoma surgery according to the maturity of the donor corneal endothelial cells. Design: Prospective cohort study. Methods: This prospective cohort study included 17 patients with glaucoma and 51 patients without glaucoma who underwent Descemet's stripping automated endothelial keratoplasty or penetrating keratoplasty at the Baptist Eye Institute, Kyoto, Japan, between October 2014 and October 2016. Human corneal endothelial cells were cultured from residual peripheral donor cornea tissue, and the maturity of the cells was evaluated by cell surface markers (ie, CD166 Results: At 36 months postoperatively, the mean ECD and ECL in the glaucoma-bleb eyes were 1197 ± 352 cells/mm Conclusions: The findings in this prospective cohort study revealed that the use of donor corneal grafts containing mature-differentiated corneal endothelial cells could maintain the survival of the transplanted graft for a long-term period, even in patients with a history of undergoing glaucoma surgery.
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80030-2
ISSN	1879-1891 ; 0002-9394
ISSN (online)	1879-1891
ISSN	0002-9394
DOI	10.1016/j.ajo.2024.01.033
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Article ; Online: Twelve-year outcome of Rho-associated protein kinase inhibitor eye drop treatment for Fuchs endothelial corneal dystrophy: A case study.

Tomioka, Yasufumi / Kitazawa, Koji / Fukuoka, Hideki / Ueno, Morio / Koizumi, Noriko / Sotozono, Chie / Kinoshita, Shigeru

American journal of ophthalmology case reports

2023 Volume 30, Page(s) 101839

Abstract: Purpose: To report the safety, efficacy, and long-term outcome in a case of Fuchs endothelial corneal dystrophy (FECD) treated by Rho-associated protein kinase (ROCK)-inhibitor eye drops in combination with removal of degenerated corneal endothelial ... ...

Abstract	Purpose: To report the safety, efficacy, and long-term outcome in a case of Fuchs endothelial corneal dystrophy (FECD) treated by Rho-associated protein kinase (ROCK)-inhibitor eye drops in combination with removal of degenerated corneal endothelial cells (CECs) subsequent to transcorneal freezing. Observations: A 52-year-old Japanese man diagnosed with early-stage FECD developed central corneal edema with decreased visual acuity (VA) in his left eye and was treated by ROCK inhibitor eye drops (Y-27632 10mM) q.i.d. for 1 week starting immediately subsequent to the removal of the damaged CECs via 2-mm-diameter transcorneal freezing in May 18, 2010. Before treatment, the best-corrected VA (BCVA) was 20/20 OD and 20/63 OS, and the central corneal thickness in the left eye was 643 μm and specular microscopy image at the central cornea was not detected due to edema. Corneal transparency recovered, and the BCVA improved to 20/20 within two weeks. At 12 years post treatment, the cornea in left eye remained transparent without corneal edema, and the CEC density at the central cornea was 1294 cells/mm Conclusions and importance: The findings in this case suggest the potential long-term safety and efficacy of the medical therapy by ROCK-inhibitor eye drop for early-stage FECD.
Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Case Reports
ISSN	2451-9936
ISSN (online)	2451-9936
DOI	10.1016/j.ajoc.2023.101839
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Article: Current Evidence for Corynebacterium on the Ocular Surface

Aoki, Takanori / Kitazawa, Koji / Deguchi, Hideto / Sotozono, Chie

Microorganisms. 2021 Jan. 27, v. 9, no. 2

2021

Abstract: Corynebacterium species are commonly found in the conjunctiva of healthy adults and are recognized as non-pathogenic bacteria. In recent years, however, Corynebacterium species have been reported to be potentially pathogenic in various tissues. We ... ...

Abstract	Corynebacterium species are commonly found in the conjunctiva of healthy adults and are recognized as non-pathogenic bacteria. In recent years, however, Corynebacterium species have been reported to be potentially pathogenic in various tissues. We investigated Corynebacterium species on the ocular surface and reviewed various species of Corynebacterium in terms of their antimicrobial susceptibility and the underlying molecular resistance mechanisms. We identified a risk for Corynebacterium-related ocular infections in patients with poor immunity, such as patients with diabetes or long-term users of topical steroids, and in those with corneal epithelial damage due to trauma, contact lens wear, lagophthalmos, and trichiasis. The predominant strain in the conjunctiva was C. macginleyi, and the species associated with keratitis and conjunctivitis were C. macginleyi, C. propinquum, C. mastitidis, C. pseudodiphtheriticum, C. accolens, C. striatum, C. xerosis, and C. bovis. Overall, Corynebacterium species present on the ocular surface were resistant to quinolones, whereas those in the nasal cavity were more susceptible. The prevalence of fluoroquinolone-resistant Corynebacterium has not changed in the past 10 years; however, Corynebacterium species remain susceptible to third-generation cephems. In conclusion, the use of third-generation cephems should be a reasonable and pragmatic approach for treatment of ocular infections caused by Corynebacterium species.
Keywords	antibiotic resistance ; conjunctiva ; conjunctivitis ; cornea ; diabetes ; epithelium ; immunity ; keratitis ; nasal cavity ; quinolones ; risk
Language	English
Dates of publication	2021-0127
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9020254
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Biologic Character of Donor Corneal Endothelial Cells Influences Endothelial Cell Density Post Successful Corneal Transplantation.

Kitazawa, Koji / Toda, Munetoyo / Ueno, Morio / Uehara, Asako / Sotozono, Chie / Kinoshita, Shigeru

Ophthalmology science

2022 Volume 3, Issue 2, Page(s) 100239

Abstract: Purpose: Corneal endothelial cell density (ECD) gradually decreases after corneal transplantation by unknown biologic, biophysical, or immunologic mechanism. Our purpose was to assess the association between donor corneal endothelial cell (CEC) maturity ...

Abstract	Purpose: Corneal endothelial cell density (ECD) gradually decreases after corneal transplantation by unknown biologic, biophysical, or immunologic mechanism. Our purpose was to assess the association between donor corneal endothelial cell (CEC) maturity in culture and postoperative endothelial cell loss (ECL) after successful corneal transplantation. Design: Prospective cohort study. Participants: This cohort study was conducted at Baptist Eye Institute, Kyoto, Japan, between October 2014 and October 2016. It included 68 patients with a 36-month follow-up period who had undergone successful Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty. Methods: Human CECs (HCECs) from remaining peripheral donor corneas were cultured and evaluated for maturity by surface markers (CD166 Main outcome measures: Endothelial cell density and ECL at 36 months postoperative. Results: The 68 included patients (mean [standard deviation] age 68.1 [13.6] years, 47.1% women, 52.9% DSAEK). The high, middle, and low-maturity groups included 17, 32, and 19 eyes, respectively. At 36 months postoperative, the mean (standard deviation) ECD significantly decreased to 911 (388) cells/mm Conclusions: The high content of mature-differentiated HCECs expressed in culture by the donor peripheral cornea was coincident with low ECL, suggesting that a high-maturity CEC content predicts long-term graft survival. Understanding the molecular mechanism for maintaining HCEC maturity could elucidate the mechanism of ECL after corneal transplantation and aid in developing effective interventions. Financial disclosures: Proprietary or commercial disclosure may be found after the references.
Language	English
Publishing date	2022-10-28
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-9145
ISSN (online)	2666-9145
DOI	10.1016/j.xops.2022.100239
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Article ; Online: Does senescence play a role in age-related macular degeneration?

Malek, Goldis / Campisi, Judith / Kitazawa, Koji / Webster, Corey / Lakkaraju, Aparna / Skowronska-Krawczyk, Dorota

Experimental eye research

2022 Volume 225, Page(s) 109254

Abstract: Advanced age is the most established risk factor for developing age-related macular degeneration (AMD), one of the leading causes of visual impairment in the elderly, in Western and developed countries. Similarly, after middle age, there is an ... ...

Abstract	Advanced age is the most established risk factor for developing age-related macular degeneration (AMD), one of the leading causes of visual impairment in the elderly, in Western and developed countries. Similarly, after middle age, there is an exponential increase in pathologic molecular and cellular events that can induce senescence, traditionally defined as an irreversible loss of the cells' ability to divide and most recently reported to also occur in select post-mitotic and terminally differentiated cells, such as neurons. Together these facts raise the question as to whether or not cellular senescence, may play a role in the development of AMD. A number of studies have reported the effect of ocular-relevant inducers of senescence using primarily in vitro models of poorly polarized, actively dividing retinal pigment epithelial (RPE) cell lines. However, in interpretating the data, the fidelity of these culture models to the RPE in vivo, must be considered. Fewer studies have explored the presence and/or impact of senescent cells in in vivo models that present with phenotypic features of AMD, leaving this an open field for further investigation. The goal of this review is to discuss current thoughts on the potential role of senescence in AMD development and progression, with consideration of the model systems used and their relevance to human disease.
MeSH term(s)	Middle Aged ; Humans ; Aged ; Retinal Pigment Epithelium/metabolism ; Macular Degeneration/metabolism ; Cellular Senescence
Language	English
Publishing date	2022-09-21
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2022.109254
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Article ; Online: Gene expression signatures of human senescent corneal and conjunctival epithelial cells.

Kitazawa, Koji / Matsumoto, Akifumi / Numa, Kohsaku / Tomioka, Yasufumi / Zhang, Zhixin A / Yamashita, Yohei / Sotozono, Chie / Desprez, Pierre-Yves / Campisi, Judith

Aging

2023 Volume 15, Issue 18, Page(s) 9238–9249

Abstract: Purpose: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells.: Methods: We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression ...

Abstract	Purpose: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. Methods: We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated. Results: X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation. Conclusion: This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.
MeSH term(s)	Humans ; Transcriptome ; Limbus Corneae/pathology ; Cornea/metabolism ; Epithelial Cells/metabolism ; Conjunctiva
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.205113
Database	MEDical Literature Analysis and Retrieval System OnLINE

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