scholarly journals Remodeling of the Corneal Epithelial Scaffold for Treatment of Persistent Epithelial Defects in Diabetic Keratopathy

2018 ◽  
Vol 9 (2) ◽  
pp. 333-340
Author(s):  
Manami Ohta ◽  
Yukiko Morita ◽  
Naoyuki Yamada ◽  
Teruo Nishida ◽  
Naoyuki Morishige

Background: To develop a strategy based on surgical removal of a degenerated corneal epithelial scaffold for treatment of persistent epithelial defects (PEDs) in diabetic keratopathy. Case Presentation: Three diabetic patients with PEDs were initially treated with eyedrops containing the fibronectin-based peptide PHSRN (Pro-His-Ser-Arg-Asn) or both the substance P-derived peptide FGLM-NH2 and the insulin-like growth factor-1-derived peptide SSSR. A degenerated Bowman’s layer or calcified lesion thought to be responsible for incomplete healing was surgically removed after confirmation of reactivity to the peptide eyedrops. All three patients achieved complete epithelial wound closure after surgery. Two cases treated by phototherapeutic keratectomy or lamellar keratoplasty did not show PED recurrence during 6 or 36 months of follow-up, respectively. One case treated by mechanical removal of a degenerated Bowman’s layer manifested recurrence after 1 month, but resurfacing of the defect was again achieved after repeat surgery. Conclusion: We propose a new strategy for treatment of diabetic PEDs based on surgical remodeling of the corneal epithelial scaffold for patients who respond to peptide eyedrops but fail to achieve wound closure.

Author(s):  
Kamonnaree Chotinantakul ◽  
Chavaboon Dechsukhum ◽  
Duangnapa Dejjuy ◽  
Wilairat Leeanansaksiri

AbstractDiabetes can impair wound closure, which can give rise to major clinical problems. Most treatments for wound repair in diabetes remain ineffective. This study aimed to investigate the influence on wound closure of treatments using expanded human cord blood CD34+ cells (CB-CD34+ cells), freshly isolated CB-CD34+ cells and a cytokine cocktail. The test subjects were mice with streptozotocin-induced diabetes. Wounds treated with fresh CB-CD34+ cells showed more rapid repair than mice given the PBS control. Injection of expanded CB-CD34+ cells improved wound closure significantly, whereas the injection of the cytokine cocktail alone did not improve wound repair. The results also demonstrated a significant decrease in epithelial gaps and advanced re-epithelialization over the wound bed area after treatment with either expanded CB-CD34+ cells or freshly isolated cells compared with the control. In addition, treatments with both CB-CD34+ cells and the cytokine cocktail were shown to promote recruitment of CD31+-endothelial cells in the wounds. Both the CB-CD34+ cell population and the cytokine treatments also enhanced the recruitment of CD68-positive cells in the early stages (day 3) of treatment compared with PBS control, although the degree of this enhancement was found to decline in the later stages (day 9). These results demonstrated that expanded CB-CD34+ cells or freshly isolated CB-CD34+ cells could accelerate wound repair by increasing the recruitment of macrophages and capillaries and the reepithelialization over the wound bed area. Our data suggest an effective role in wound closure for both ex vivo expanded CB-CD34+ cells and freshly isolated cells, and these may serve as therapeutic options for wound treatment for diabetic patients. Wound closure acceleration by expanded CB-CD34+ cells also breaks the insufficient quantity obstacle of stem cells per unit of cord blood and other stem cell sources, which indicates a broader potential for autologous transplantation.


2020 ◽  
Author(s):  
Jake D. Callaghan ◽  
Nicholas A. Stella ◽  
Kara M. Lehner ◽  
Benjamin R. Treat ◽  
Kimberly M. Brothers ◽  
...  

ABSTRACTTunable control of gene expression is an invaluable tool for biological experiments. In this study, we describe a new xylose-inducible promoter system and evaluate it in both Pseudomonas aeruginosa and P. fluorescens. The Pxut promoter derived from the P. flurorescens xut operon was incorporated into a broad host-range pBBR1-based plasmid and compared to the Escherichia coli-derived PBAD promoter using gfp as a reporter. GFP-fluorescence from the Pxut promoter was inducible in both Pseudomonas species, but not in E. coli, which may facilitate cloning of toxic genes using E. coli to generate plasmids. The Pxut promoter was expressed at a lower inducer concentration than PBAD in P. fluorescens and higher gfp levels were achieved using Pxut. Flow cytometry analysis indicated that Pxut was more leaky than PBAD in the tested Pseudomonas species, but was expressed in a higher proportion of cells when induced. D-xylose did not support growth of P. aeruginosa or P. fluorescens as a sole carbon source and is less expensive than many other commonly used inducers which could facilitate large scale applications. The efficacy of this system aided in demonstrating a role for the P. aeruginosa type II secretion system gene from xcpQ in bacterial inhibition of corneal epithelial cell wound closure. This study introduces a new inducible promoter system for gene expression for use in Pseudomonas species.ImportancePseudomonas species are enormously important in human infections, biotechnology, and as a model system for interrogating basic science questions. In this study we have developed a xylose-inducible promoter system and evaluated it in P. aeruginosa and P. fluorescens and found it to be suitable for the strong induction of gene expression. Furthermore, we have demonstrated its efficacy in controlled gene expression to show that a type 2 secretion system protein from P. aeruginosa, XcpQ, is important for host-pathogen interactions in a corneal wound closure model.


Food Research ◽  
2021 ◽  
Vol 5 (4) ◽  
pp. 394-403
Author(s):  
T.M. Ting ◽  
J.H. King ◽  
K.L. Ho ◽  
H.L.N. Lau

Diabetic patients often experience problems with their immune system activation and result in delayed wound healing. Slow and incomplete wound healing increases the risk of complications caused by infected wounds. Metformin has been used as a standard drug for diabetes treatment and it accelerates wound healing. However, intake of metformin may cause gastrointestinal symptoms including diarrhoea, nausea and abdominal discomfort. Therefore, a safe alternative to metforminis is required. While many research programs focus on alpha-tocopherol, in this paper the potency of tocotrienols in wound and diabetes management was investigated. Tocotrienol rich fraction (TRF) was tested for its ability to stabilize blood glucose, reduce lipid peroxidation, promote platelet-derived growth factorBB and wound closure. In this study, the rodent model was used to investigate the effects of TRP in wound healing proficiency. The results showed that TRF was comparable to metformin in stabilizing blood glucose, promoting PDGF-BB in the blood during the initial wound healing stage and produced clean wound closure. Interestingly, the findings of this study showed TRF had higher potency than metformin in reducing lipid peroxidation that could delay wound healing. Hence, TRF could be a good alternative to metformin in wound and diabetes management


2021 ◽  
Vol 8 (1) ◽  
pp. 1-9
Author(s):  
Alfonso L Sabater ◽  

Autologous blood eye drops have become an interesting, well-known, and widely used therapeutic option for many ocular surface diseases since their introduction into the ophthalmologic field forty-six years ago. The foundation for their use in the treatment of pathologies such as severe keratoconjunctivitis sicca, persistent epithelial defects, ocular chemical burns, recurrent epithelial erosions, Stevens-Johnson syndrome, ocular graft versus host disease, and, lately, in many other ocular surface conditions, relies on the fact that they contain proteins, vitamins, cytokines, and growth factors that participate in the signaling pathways of corneal epithelial healing in similar amounts to those found in normal, healthy tear films


2021 ◽  
pp. 112067212110590
Author(s):  
Cristina Monterosso ◽  
Marco Antonini ◽  
Antonio Di Zazzo ◽  
Daniele Gaudenzi ◽  
Luigi Caretti ◽  
...  

Purpose To evaluate postoperative safety of femtosecond laser deep anterior lamellar keratoplasty performed with an innovative anvil profile in keratoconus patients. Methods This is a single-center, retrospective cohort study. We reviewed medical records of 89 keratoconus patients that underwent femtosecond laser deep anterior lamellar keratoplasty surgery (46 eyes) and manual deep anterior lamellar keratoplasty (47 eyes). Inclusion criteria required: age > 18 years old, best-corrected visual acuity < 0.3 LogMAR, continuous suture of the graft, postoperative immunomodulant regimen with dexamethasone 0.1% for 6 months and at least 12 months follow-up. Previous eye surgery, hydrops, and other ocular disease were excluded. The main outcome measures were postoperative events: rejections, persistent epithelial defects, and graft failures. Results During the follow-up (20 ± 6 months) graft rejection was diagnosed in 0 of femtosecond laser deep anterior lamellar keratoplasty versus 6 (17%) of manual deep anterior lamellar keratoplasty [ p 0.027], persistent epithelial defect in 0 of femtosecond laser deep anterior lamellar keratoplasty versus in 4 (11%) of manual deep anterior lamellar keratoplasty [ p 0.048] and graft failure occurred in 4 (11%) of manual deep anterior lamellar keratoplasty. The best-corrected visual acuity, after removal of sutures, was better in the femtosecond laser deep anterior lamellar keratoplasty group 0.09 ± 0.08 LogMAR versus 0.16 ± 0.13 LogMAR in manual deep anterior lamellar keratoplasty [ p 0.035] group although refractive spherical equivalent and cylinder, topographic average keratometry and cylinder were similar. Conclusions Anvil-shaped femtosecond laser deep anterior lamellar keratoplasty in keratoconus surgery increases safety and readiness of recovery, decreasing the incidence of corneal rejection, epithelial defects, graft failures, and producing better best-corrected visual acuity after removal of sutures.


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