Efficacy of Modified Amnion-Assisted Conjunctival Epithelial Redirection (ACER) for Partial Limbal Stem Cell Deficiency

Background and objectives: the aim of this study was to analyze the efficacy of a modified “amnion-assisted conjunctival epithelial redirection (ACER)” technique for the treatment of partial limbal stem cell deficiency (LSCD). Materials and methods: the medical records of three patients with partial LSCD who underwent corneal surface reconstruction with modified ACER following superficial keratectomy were retrospectively studied. Briefly, in this technique, an inner amniotic membrane (AM) layer was applied on the corneal surface to promote corneal re-epithelialization. The outer AM layer was applied as a barrier to prevent the invasion of conjunctival epithelial cells into the cornea before the corneal surface was completely covered by corneal epithelial cells derived from the remaining intact limbal stem cells. Results: in all three cases, the outer AM layer successfully kept the conjunctival epithelium away from the corneal surface and prevented an admixture of conjunctival epithelial cells with corneal epithelial cells. In all three patients, the cornea was completely re-epithelized with epithelial cells derived from the remaining healthy limbal stem cells, and a clear visual axis was maintained without recurrence for a mean follow-up period of 37.3 ± 8.6 months. Conclusions: the preliminary results suggest that modified ACER appears to be a viable option for patients with partial LSCD.

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Clinical Outcomes of Modified Simple Limbal Epithelial Transplantation for Limbal Stem Cell Deficiency in Chinese Population: A Retrospective Case Series

10.21203/rs.3.rs-313221/v1 ◽

2021 ◽

Author(s):

Yinghui Wang ◽

Xiaodan Hu ◽

Ke Yang ◽

Yang Zhang ◽

Shijing Deng ◽

...

Keyword(s):

Stem Cell ◽

Epithelial Cells ◽

Clinical Outcomes ◽

Case Series ◽

Limbal Stem Cell Deficiency ◽

Successful Outcome ◽

Limbal Stem Cells ◽

Corneal Epithelial Cells ◽

Corneal Epithelial ◽

Limbal Stem Cell

Abstract Objective To report clinical outcomes of a novel surgical technique, namely simple limbal epithelial transplantation (SLET), for the treatment of limbal stem cell deficiency (LSCD). Methods 13 patients (13 eyes) with LSCD who underwent autologous (10 eyes) or allogeneic (3 eyes) modified SLET between 2018 and 2021 were enrolled in this study. Grades of symblepharon, corneal conjunctivalisation, vascularisation, opacification, and visual acuity (VA) were evaluated preoperatively and postoperatively. In 2 cases, in vivo confocal microscopy (IVCM) and impression cytology (IC) were performed to assess the proliferation and degeneration of limbal tissue. Results At a postoperative follow-up of 6.5 ± 5.3 (range, 2–20) months, 10 (10/13, 76.92%) eyes maintained a successful outcome. The grades of symblepharon, corneal conjunctivalisation, vascularisation, and opacification were significantly improved after SLET (P < 0.05). Two-line improvement in VA was found in 6 (6/10, 60%) eyes of the successful cases. Recurrence of LSCD occurred in 3 (3/13, 23.08%) eyes and conjunctival cyst occurred in 1 patient. After SLET, morphology and structure of corneal epithelial cells and epithelial transition around the limbal tissue fragments were detected by IVCM and IC. Conclusions Our findings suggest that the SLET is a safe and effective technique for the treatment of LSCD. The corneal stroma and hAM can provide protection and nutrition for the limbal stem cells (LSCs) without negatively influencing clinical outcomes. IVCM and IC after SLET can evaluate the effectiveness of surgery and the transition of LSCs and corneal epithelial cells.

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Clinical outcomes of modified simple limbal epithelial transplantation for limbal stem cell deficiency in Chinese population: a retrospective case series

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02345-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yinghui Wang ◽

Xiaodan Hu ◽

Ke Yang ◽

Yang Zhang ◽

Shijing Deng ◽

...

Keyword(s):

Stem Cell ◽

Epithelial Cells ◽

Clinical Outcomes ◽

Case Series ◽

Limbal Stem Cell Deficiency ◽

Successful Outcome ◽

Limbal Stem Cells ◽

Corneal Epithelial Cells ◽

Corneal Epithelial ◽

Limbal Stem Cell

Abstract Objective To report the clinical outcomes of a novel surgical technique, namely simple limbal epithelial transplantation (SLET), for the treatment of limbal stem cell deficiency (LSCD). Methods Thirteen patients (13 eyes) with LSCD who underwent autologous (10 eyes) or allogeneic (3 eyes) modified SLET between 2018 and 2021 were enrolled in this study. Grades of symblepharon, corneal conjunctivalization, vascularization, opacification, and visual acuity (VA) were evaluated preoperatively and postoperatively. In 2 cases, in vivo confocal microscopy (IVCM) and impression cytology (IC) were performed to assess the proliferation and degeneration of limbal tissue. Results At a postoperative follow-up of 6.5±5.3 (range, 2–20) months, 10 (10/13, 76.92%) eyes maintained a successful outcome. The grades of symblepharon, corneal conjunctivalization, vascularization, and opacification were significantly improved after SLET (P<0.05). Two-line improvement in VA was found in 6 (6/10, 60%) eyes of the successful cases. Recurrence of LSCD occurred in 3 (3/13, 23.08%) eyes, and conjunctival cyst occurred in 1 patient. After SLET, the morphology and structure of corneal epithelial cells and epithelial transition around the limbal tissue fragments were detected by IVCM and IC. Conclusions Our findings suggest that the SLET is a safe and effective technique for the treatment of LSCD. The corneal stroma and hAM can provide protection and nutrition for the limbal stem cells (LSCs) without negatively influencing the clinical outcomes. IVCM and IC after SLET can evaluate the effectiveness of surgery and the transition of LSCs and corneal epithelial cells.

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Stem Cell-Like Characteristics of Corneal Epithelial Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.998-999.312 ◽

2014 ◽

Vol 998-999 ◽

pp. 312-315

Author(s):

Fan Wang ◽

Bo Ren ◽

Yi Ning Yan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Epithelial Cells ◽

Corneal Epithelium ◽

Cell Activity ◽

Stem Cell Marker ◽

Corneal Tissue ◽

Limbal Stem Cells ◽

Corneal Epithelial Cells ◽

Corneal Epithelial

Purpose: The adult corneal epithelium is maintained by a population of limbal stem cells (LSCs), transmembrane protein prominin, regarded as stem cell marker was investigated on mouse corneal tissue, to study weather contains CD133-expressing cells and their distribution. Methods: Enucleated mouse eyes were embedded in OCT and cryosections were performed for mmunohistochemical studies using the avidin-biotin-peroxidase complex (ABC) procedure. Meanwhile, dissected mouse corneas were analyzed by westernblot. Results: In the adult mouse, 13A4 immunoreactivity was detected at the apical side of superficial corneal epithelium, including the limbus region, but not by stroma and endothelium. 115 KDa protein was approved in corneal tissue by Westernblot. Conclusions: The stem cell activity does not occur along the limbus but presumably presented by small portion of corneal epithelial cells which may hold a similar properties of stem cells.

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Plasma Polymer-Coated Contact Lenses for the Culture and Transfer of Corneal Epithelial Cells in the Treatment of Limbal Stem Cell Deficiency

Tissue Engineering Part A ◽

10.1089/ten.tea.2013.0089 ◽

2014 ◽

pp. 140123085146001 ◽

Cited By ~ 4

Author(s):

Karl David Brown ◽

Suet Low ◽

Indumathi Mariappan ◽

Keren Maree Abberton ◽

Robert Short ◽

...

Keyword(s):

Stem Cell ◽

Epithelial Cells ◽

Contact Lenses ◽

Limbal Stem Cell Deficiency ◽

Plasma Polymer ◽

Corneal Epithelial Cells ◽

Corneal Epithelial ◽

Limbal Stem Cell

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Proteasome and Autophagy Pathway in Corneal Epithelial Cells with Limbal Stem Cell Deficiency

International Journal of Ophthalmology and Clinical Research ◽

10.23937/2378-346x/1410112 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Bardag-Gorce Fawzia ◽

Lorenzo Michael Di ◽

Niihara Robert ◽

Sunada Sarah ◽

Laporte Amanda ◽

...

Keyword(s):

Stem Cell ◽

Epithelial Cells ◽

Limbal Stem Cell Deficiency ◽

Corneal Epithelial Cells ◽

Corneal Epithelial ◽

Autophagy Pathway ◽

Limbal Stem Cell

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Corneal epithelial changes following reconstruction by transplantation of limbal stem cells in goats with total limbal stem cell deficiency

Cell Research ◽

10.1038/cr.2008.162 ◽

2008 ◽

Vol 18 (S1) ◽

pp. S72-S72

Author(s):

Shengli Mi ◽

Zhongying Dou ◽

Qingmei Zhao ◽

Xueyi Yang ◽

Lei Qu ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Limbal Stem Cell Deficiency ◽

Limbal Stem Cells ◽

Corneal Epithelial ◽

Limbal Stem Cell

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Cornea and Lens Problems in Aniridia

Aniridia and WAGR Syndrome ◽

10.1093/oso/9780195389302.003.0010 ◽

2010 ◽

Author(s):

Edward J. Holland ◽

Mayank Gupta

Keyword(s):

Stem Cells ◽

Epithelial Cells ◽

Corneal Epithelium ◽

Basal Layer ◽

Limbal Stem Cells ◽

Corneal Epithelial Cells ◽

Film Stability ◽

Corneal Epithelial ◽

Corneal Erosion ◽

Peripheral Cornea

The corneal epithelium is a rapidly regenerating, stratified squamous epithelium. Homeostasis of corneal epithelial cells is an important prerequisite, not only for the integrity of the ocular surface, but also for the visual function. The maintenance of a healthy corneal epithelium under both normal and wound-healing conditions is achieved by a population of stem cells located in the basal layer of limbal epithelium. The Limbus represents the transition zone between the peripheral cornea and the bulbar conjunctiva. The stem cells from the limbus generate the transient amplifying cells that migrate, proliferate, and differentiate to replace lost or damaged corneal epithelial cells. In patients with aniridia, there is a primary dysfunction of these limbal stem cells (see Figure 6.1). The cornea is affected clinically in 90 percent of the patients with aniridia. In most cases, the cornea in aniridic patients appears normal and transparent during infancy and childhood. However, during the early teens, the cornea begins to show changes. The early changes are marked by the in-growth of opaque epithelium from the limbal region into the peripheral cornea, which represents conjunctival epithelial cells, goblet cells, and blood vessels in the corneal epithelium. These changes gradually progress toward the central cornea and may cause corneal epithelial erosions and epithelial abnormalities that eventually culminate in opacification of the corneal stroma, which leads to vision loss. With the gradual loss of limbal stem cells, the entire cornea becomes covered with conjunctival cells. Eventually, many patients develop total limbal stem cell deficiency. These abnormalities usually become more pronounced with aging. The corneal abnormalities seen in aniridia are collectively termed “aniridic keratopathy”. Significant corneal opacification may occasionally be the initial manifestation of aniridia. Abnormal tear film stability and meibomian gland dysfunction are also observed in patients with aniridia. This can lead to dry eyes, aggravating corneal erosion and ulceration observed in aniridic patients. Sometimes, aniridia is associated with “Peter’s anomaly,” in which central corneal opacity is present at birth along with defects in the corneal endothelium and Descemet’s membrane.

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Subconjunctival Injection of Transdifferentiated Oral Mucosal Epithelial Cells for Limbal Stem Cell Deficiency in Rats

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155420980071 ◽

2020 ◽

pp. 002215542098007

Author(s):

Yu-Ting Xiao ◽

Hua-Tao Xie ◽

Xin Liu ◽

Chao-Ye Duan ◽

Jing-Yu Qu ◽

...

Keyword(s):

Stem Cell ◽

Epithelial Cells ◽

Pigment Epithelium ◽

Limbal Stem Cell Deficiency ◽

Subconjunctival Injection ◽

Epithelial Defect ◽

Corneal Epithelial ◽

Corneal Epithelial Defect ◽

Limbal Stem Cell

Rat limbal niche cells (LNCs) have been proven to induce transdifferentiation of oral mucosal epithelial cells (OMECs) into corneal epithelial-like cells termed transdifferentiated oral mucosal epithelial cells (T-OMECs). This investigation aimed to evaluate the effect of subconjunctival T-OMEC injections on alkali-induced limbal stem cell deficiency (LSCD) in rats. LNCs were cocultured with OMECs in the Transwell system to obtain T-OMECs, with NIH-3T3 cells serving as a control. Subconjunctival injection of single T-OMEC or OMEC suspension was performed immediately after corneal alkali injury. T-OMECs were prelabeled with the fluorescent dye CM-DiI in vitro and tracked in vivo. Corneal epithelial defect, opacity, and neovascularization were quantitatively analyzed. The degree of corneal epithelial defect (from day 1 onward), opacity (from day 5 onward), and neovascularization (from day 2 onward) was significantly less in the T-OMEC group than in the OMEC group. Cytokeratin 12 (CK12), pigment epithelium–derived factor, and soluble fms-like tyrosine kinase-1 were expressed at a higher rate following T-OMEC injection. Some CM-DiI-labeled cells were found to be coexpressed with CK12, Pax6, and ΔNp63α in the corneal epithelium after subconjunctival injection. Subconjunctival injection of T-OMECs prevents conjunctival invasion and maintains a normal corneal phenotype, which might be a novel strategy in the treatment of LSCD:

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