Regeneration of the Corneal Endothelium

Okumura, Naoki; Koizumi, Noriko

doi:10.1080/02713683.2019.1700529

Cited by 34 publications

(29 citation statements)

References 94 publications

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“…Considering that demand for donor corneas surpasses the supply, researchers have been trying to uncover the deeper and wider mechanisms of injured CECs so as to provide the base for alternative therapeutic methods to alleviate the injurious process. Adult human CECs cannot proliferate in vivo, and ex vivo culture is passage limitation with EMT risks 2,6 . Moreover, due to their monolayer cellular structural features, adequate corneal endothelial primary cells are not readily available for experiments 1 .…”

Section: Discussionmentioning

confidence: 99%

“…Corneal endothelial cells (CECs) locate at the innermost layer of the cornea, which are essential for corneal transparency due to its barrier and ionic "pump" function 1 . The cell cycle of human CECs (hCECs) is arrested at the G1 phase, and hCECs cannot divide in vivo 2,3 . Under normal conditions, though there is an average loss rate of 0.3-0.6% CECs per year, adjacent cells may cover the wound area by spreading and/or migrating.…”

Section: Introductionmentioning

confidence: 99%

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PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

Zhang

Yan

et al. 2020

Cell Death Dis

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Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits corneal endothelial defects. However, the effects of PAX6 protein involved in corneal endothelial wound process are still unknown. Here, we found the upregulated protein levels of PAX6 in human corneal endothelial monolayer after injury; the expression of PAX6 also increased in murine and rat corneal endothelium injury models. Enforced PAX6 expression could alleviate the damages to CECs via regulating permeability by prompting cellular tight junction. In addition, SUMOylation mainly happened on both K53 and K89 residues of 48-kD PAX6 (the longest and main isoform expressed in cornea), and de-SUMOylation promoted the stability of PAX6 protein in vitro. In CECs of SENP1 +/− mice, increased SUMOylation levels leading to instability and low expression of PAX6, delayed the repair of CECs after injury. Furthermore, overexpression of PAX6 accelerated the rate of corneal endothelial repair of SENP1 +/− mice. Our findings indicate that SENP1mediated de-SUMOylation improving the stability of PAX6, amplifies the protective effects of PAX6 on corneal endothelial injuries, highlighting potentials of PAX6 and/or SUMOylation to be used as a treatment target for corneal endothelial disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

Zhang

Yan

et al. 2020

Cell Death Dis

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“…Cell therapy for treating corneal endothelial decompensation has been investigated by many research groups 7 . Indeed, a clinical trial involving injection of cultured corneal endothelial cells into the anterior chamber of the eye has been initiated in Japan 8 .…”

Section: Background and Summarymentioning

confidence: 99%

Transcriptome dataset of human corneal endothelium based on ribosomal RNA-depleted RNA-Seq data

et al. 2020

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The corneal endothelium maintains corneal transparency; consequently, damage to this endothelium by a number of pathological conditions results in severe vision loss. Publicly available expression databases of human tissues are useful for investigating the pathogenesis of diseases and for developing new therapeutic modalities; however, databases for ocular tissues, and especially the corneal endothelium, are poor. Here, we have generated a transcriptome dataset from the ribosomal RNA-depleted total RNA from the corneal endothelium of eyes from seven Caucasians without ocular diseases. The results of principal component analysis and correlation coefficients (ranged from 0.87 to 0.96) suggested high homogeneity of our RNA-Seq dataset among the samples, as well as sufficient amount and quality. The expression profile of tissue-specific marker genes indicated only limited, if any, contamination by other layers of the cornea, while the Smirnov-Grubbs test confirmed the absence of outlier samples. The dataset presented here should be useful for investigating the function/dysfunction of the cornea, as well as for extended transcriptome analyses integrated with expression data for non-coding RNAs.

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“…Corneal transplantation, such as penetrating keratoplasty (PKP) and corneal endothelial keratoplasty, is an effective way for treating corneal blindness [3,4]. Corneal endothelial dysfunction is the leading indication for endothelial keratoplasty which account for about 39% of all corneal transplantation [5,6].…”

Section: Introductionmentioning

confidence: 99%

Long-term observation and sequencing analysis of SKPs-derived corneal endothelial cell-like cells for treating corneal endothelial dysfunction

Shen

Sun

et al. 2020

Preprint

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Background Corneal endothelial dysfunction is a principal cause of visual deficiency. Corneal transplantation is the most effective treatment for corneal endothelial dysfunction. However, a severe shortage of available donor corneas remains a global challenge. Previously, we acquired corneal endothelial cell-like cells (CEC-like cells) derived from skin-derived precursors (SKPs). CEC-like cells exerted excellent therapeutic effect in rabbit and monkey corneal endothelial dysfunction models. Method: We prolonged the observation in the monkey experiment for 2 years. Further transcriptome sequencing was also carried out on HCEC, CEC-like cells before transplantation and after transplantation. Results We confirmed that the monkey cornea remained transparent and the CEC-like cells could adapt to the microenvironment after transplantation. The gene expression pattern of CEC-like cells was similar to HCEC and changed slightly after transplantation. Conclusions This study presented a brand-new insight into CEC-like cells and further provided a promising prospect of cell-based therapy for corneal endothelial dysfunction. The renewable cell source, novel derivation method and simple treatment strategy may be clinically applied in regenerative medicine in the future.

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Regeneration of the Corneal Endothelium

Cited by 34 publications

References 94 publications

PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

Transcriptome dataset of human corneal endothelium based on ribosomal RNA-depleted RNA-Seq data

Long-term observation and sequencing analysis of SKPs-derived corneal endothelial cell-like cells for treating corneal endothelial dysfunction

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