Approaches for corneal endothelium regenerative medicine

Català, Pere; Thuret, Gilles; Skottman, Heli; Mehta, Jodhbir S.; Parekh, Mohit; Dhubhghaill, Sorcha Ní; Collin, Rob W.J.; Nuijts, Rudy M.M.A.; Ferrari, Stefano; LaPointe, Vanessa; Dickman, Mor M.

doi:10.1016/j.preteyeres.2021.100987

Cited by 43 publications

(49 citation statements)

References 233 publications

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“…Nearly 13 million people worldwide are awaiting a corneal transplantation, for which CE impairment represents the main indication [ 2 ]. For decades researchers have been seeking the key to induce CEnCs to proliferate, which is the principal hindrance that still hampers the clinical application of a regenerative strategy to repair CE damages [ 1 ]. However, CEnCs proliferation has not been described to date by expression of specific markers: CEnCs characterization markers commonly used are not tissue specific and not clearly associated to CE intracellular processes [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Differently from the actively proliferating CEnCs, the cells isolated from the tissue, which are in a quiescent stage in vivo [ 1 ], demonstrated very low levels of LAP2α and β. ( Figure 1 d).…”

Section: Discussionmentioning

confidence: 99%

“…Its dysfunction is responsible for corneal swelling and opacification, hence severely impairing correct vision. The state of the art for treating CE damages is corneal transplantation, the most frequent type of transplantation performed worldwide [ 1 ] and for which CE impairment represents the main indication. However, it is a complex surgical procedure, further limited by shortage of donor corneas and a considerable risk of graft detachment or allogenic rejection [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…The state of the art for treating CE damages is corneal transplantation, the most frequent type of transplantation performed worldwide [ 1 ] and for which CE impairment represents the main indication. However, it is a complex surgical procedure, further limited by shortage of donor corneas and a considerable risk of graft detachment or allogenic rejection [ 1 ]. As a result of the long waiting list for corneal transplantation (only 1 in 70 people in need are covered, with 12.7 million people awaiting) [ 2 ], researches are seeking novel more effective treatments based on regenerative medicine.…”

Section: Introductionmentioning

confidence: 99%

“…Beside a morphological characterization, a precise phenotypical and genotypical signature must define HCEnCs in order to develop a solid tissue engineering-based approach. Markers generally used to characterise CEnCs identity include ZO-1, Na + K + ATPase, Collagen8 [ 1 ], SLC4A11 [ 9 ] and, more recently, CD166 that is found specifically in HCEnCs [ 1 ]. In parallel, markers such as alpha-SMA [ 10 ] or CD44 [ 9 ] and CD73 [ 11 ] are deemed detrimental as associated with EnMT in CEnCs, and should be absent.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Fluctuations in Corneal Endothelial LAP2 Expression Levels Correlate with Passage Dependent Declines in Their Cell Proliferative Activity

Maurizi

Merra

Schiroli

et al. 2022

IJMS

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The corneal endothelium is the inner corneal mono-layered epithelium, fundamental for preserving corneal hydration and transparency. However, molecular mechanisms that regulate corneal endothelial cells (CEnCs), in particular regarding their proliferative capacity, have been only partially elucidated. CEnCs are quiescent in vivo and they easily undergo endothelial to mesenchymal transition (EnMT) in vitro. This study aims to analyze CEnCs behavior and expression in vitro, either in sub-confluent growing (S) or confluent (C) CEnCs cultures. Primary rabbit and human CEnCs were cultured and used for RT-PCR, immunofluorescence or western blot analysis. These methods allowed identifying a novel molecular marker, LAP2, that is upregulated in S while downregulated in C human or rabbit CEnCs. Those results were observed for several subsequent passages in culture and this, together with the correlation between ki67 and LAP2 expression, suggested LAP2 as a novel possible indicator for culture ageing. Finally, treatment with FGF and TGFβ in rCEnCs highlighted how LAP2 can vary as the cells regulate their proliferative state. In conclusion, we have identified a novel marker for CEnCs, LAP2, that regulates its expression depending on the cells sub/confluent state and that correlates with CEnCs proliferation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Fluctuations in Corneal Endothelial LAP2 Expression Levels Correlate with Passage Dependent Declines in Their Cell Proliferative Activity

Maurizi

Merra

Schiroli

et al. 2022

IJMS

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Elucidating the Corneal Endothelial Cell Proliferation Capacity through an Interspecies Transcriptome Comparison

Català

Vivensang²,

Beek

et al. 2023

Advanced Biology

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The regenerative capacity of corneal endothelial cells (CECs) differs between species; in bigger mammals, CECs are arrested in a non‐proliferative state. Damage to these cells can compromise their function causing corneal opacity. Corneal transplantation is the current treatment for the recovery of clear eyesight, but the donor tissue demand is higher than the availability and there is a need to develop novel treatments. Interestingly, rabbit CECs retain a high proliferative profile and can repopulate the endothelium. There is a lack of fundamental knowledge to explain these differences. Gaining information on their transcriptomic variances could allow the identification of CEC proliferation drivers. In this study, human, sheep, and rabbit CECs are analyzed at the transcriptomic level. To understand the differences across each species, a pipeline for the analysis of pathways with different activities is generated. The results reveal that 52 pathways have different activity when comparing species with non‐proliferative CECs (human and sheep) to species with proliferative CECs (rabbit). The results show that Notch and TGF‐β pathways have increased activity in species with non‐proliferative CECs, which might be associated with their low proliferation. Overall, this study illustrates transcriptomic pathway‐level differences that can provide leads to develop novel therapies to regenerate the corneal endothelium.

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Nanoneedles Induce Targeted siRNA Silencing of p16 in the Human Corneal Endothelium

et al. 2022

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Nanoneedles can target nucleic acid transfection to primary cells at tissue interfaces with high efficiency and minimal perturbation. The corneal endothelium is an ideal target for nanoneedle‐mediated RNA interference therapy aimed at enhancing its proliferative capacity, necessary for tissue regeneration. This work develops a strategy for siRNA nanoninjection to the human corneal endothelium. Nanoneedles can deliver p16‐targeting siRNA to primary human corneal endothelial cells in vitro without toxicity. The nanoinjection of siRNA induces p16 silencing and increases cell proliferation, as monitored by ki67 expression. Furthermore, siRNA nanoinjection targeting the human corneal endothelium is nontoxic ex vivo, and silences p16 in transfected cells. These data indicate that nanoinjection can support targeted RNA interference therapy for the treatment of endothelial corneal dysfunction.

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Approaches for corneal endothelium regenerative medicine

Cited by 43 publications

References 233 publications

Fluctuations in Corneal Endothelial LAP2 Expression Levels Correlate with Passage Dependent Declines in Their Cell Proliferative Activity

Fluctuations in Corneal Endothelial LAP2 Expression Levels Correlate with Passage Dependent Declines in Their Cell Proliferative Activity

Elucidating the Corneal Endothelial Cell Proliferation Capacity through an Interspecies Transcriptome Comparison

Nanoneedles Induce Targeted siRNA Silencing of p16 in the Human Corneal Endothelium

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