Matrix regeneration agents improve wound healing in non-stressed human corneal epithelial cells

Robciuc, Alexandra; Arvola, Riku; Jauhiainen, Matti; Holopainen, Juha M.

doi:10.1038/eye.2017.277

Cited by 6 publications

(8 citation statements)

References 18 publications

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“…This is in accordance with the safety data obtained from more than thousands of dogs and cats treated by Clerapliq ® in Europe (TVM) and with the publications on Clerapliq ® [36]. Also, as mentioned in the introduction, the equivalent of Cleraplic ® in humans is called Cacicol ® , which is a medical device that has been successfully used for more than 50,000 patients with no reported local or systemic side effects [37][38][39].…”

Section: Discussionsupporting

confidence: 85%

Case Reports for Topical Treatment of Corneal Ulcers with a New Matrix Therapy Agent or RGTA® in Dogs

Martinez¹,

Chiappini²,

Barritault

2019

Veterinary Sciences

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Superficial corneal ulcers that fail to heal within a normal time period and are refractory to conventional therapy in dogs are common in veterinary practice. Different etiologies can lead to this result, including spontaneous chronic corneal epithelial defects (SCCEDs) and ulcerative keratitis associated with bullous keratopathy. Thus, there is an urgent need to find new therapeutic approaches such as matrix therapy replacement. To determine the efficacy of a new ophthalmic treatment (Clerapliq ® ) for SCCEDs and ulcerative keratitis associated with bullous keratopathy, a total of 11 dogs referred to the clinic because of nonhealing erosive ulcers after a classic primary treatment were enrolled to get this new treatment. Dogs underwent ophthalmic exams and 7 dogs (10 eyes) were diagnosed with superficial ulceration and 4 dogs (5 eyes) with bullous keratopathy due to endothelial dystrophy/degeneration. They received eye drops of Clerapliq ® every 3 days until recovery. The results showed that the corneas with recurrences of the ulcers were resolved predominantly by using Clerapliq ® every 3 days in 83.3% of the cases during a period of treatment ranging between 6 to 35 days. Therefore, this new approach using matrix therapy regenerating technology in treating superficial ulcers and bullous keratopathy in dogs can be successfully considered as an adjunctive therapy.

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Section: Discussionsupporting

confidence: 85%

Case Reports for Topical Treatment of Corneal Ulcers with a New Matrix Therapy Agent or RGTA® in Dogs

Martinez¹,

Chiappini²,

Barritault

2019

Veterinary Sciences

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“…Another pharmaceutical agent, which has recently gained much attention, is a new type of extracellular matrix agent called ReGeneraTingAgent or RGTA (Arvola et al, 2016; Chappelet et al, 2017; Robciuc et al, 2018). This approach consists of engineered polymers designed to protect and replace cellular signaling proteins of the extracellular matrix (ECM), such as heparan sulfate.…”

Section: Corneal Wound Healingmentioning

confidence: 99%

Corneal Repair and Regeneration: Current Concepts and Future Directions

Mobaraki

Abbasi

Vandchali

et al. 2019

Front. Bioeng. Biotechnol.

125

109

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The cornea is a unique tissue and the most powerful focusing element of the eye, known as a window to the eye. Infectious or non-infectious diseases might cause severe visual impairments that need medical intervention to restore patients' vision. The most prominent characteristics of the cornea are its mechanical strength and transparency, which are indeed the most important criteria considerations when reconstructing the injured cornea. Corneal strength comes from about 200 collagen lamellae which criss-cross the cornea in different directions and comprise nearly 90% of the thickness of the cornea. Regarding corneal transparency, the specific characteristics of the cornea include its immune and angiogenic privilege besides its limbus zone. On the other hand, angiogenic privilege involves several active cascades in which anti-angiogenic factors are produced to compensate for the enhanced production of proangiogenic factors after wound healing. Limbus of the cornea forms a border between the corneal and conjunctival epithelium, and its limbal stem cells (LSCs) are essential in maintenance and repair of the adult cornea through its support of corneal epithelial tissue repair and regeneration. As a result, the main factors which threaten the corneal clarity are inflammatory reactions, neovascularization, and limbal deficiency. In fact, the influx of inflammatory cells causes scar formation and destruction of the limbus zone. Current studies about wound healing treatment focus on corneal characteristics such as the immune response, angiogenesis, and cell signaling. In this review, studied topics related to wound healing and new approaches in cornea regeneration, which are mostly related to the criteria mentioned above, will be discussed.

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“…As for in vivo experiments, they are expensive and difficult to conduct because of the inherent variability among animals (Bentley et al, ; Buhren et al, ; Ferrington et al, ; Friedenwald & Buschke, ; Pallikaris, Papatzanaki, Stathi, Frenschock, & Georgiadis, ). Cell monolayers in vitro models are definitively less complex than the native cornea but can be of interest due to their ease and rapidity of use (Ker‐Woon, Abd Ghafar, Hui, Mohd Yusof, & Wan Ngah, ; Lu, Wang, Dai, & Lu, ; Nelson, Silverman, Lima, & Beckman, ; Rieck, Cholidis, & Hartmann, ; Robciuc, Arvola, Jauhiainen, & Holopainen, ). Recent works in the field of tissue engineering have led to the emergence of new three‐dimensional corneal equivalents.…”

Section: Introductionmentioning

confidence: 99%

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Desjardins

Couture

Germain

et al. 2019

J Tissue Eng Regen Med

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Damage to the corneal epithelium triggers important changes in the extracellular matrix (ECM) to which basal human corneal epithelial cells (hCECs) attach. These changes are perceived by integrin receptors that activate different intracellular signalling pathways, ultimately leading to re‐epithelialization of the injured epithelium. In this study, we investigated the impact of pharmacological inhibition of specific signal transduction mediators on corneal wound healing using both monolayers of hCECs and the human tissue‐engineered cornea (hTEC) as an in vitro 3D model. RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The impact of WNK1 inhibition was evaluated on the wounded hTECs as well as on hCECs monolayers using a scratch wound assay. Gene profiling and protein kinase arrays revealed that expression and activity of several mediators from the integrin‐dependent signaling pathways were altered in response to the ECM changes occurring during corneal wound healing. Phosphorylation of the WNK1 kinase turned out to be the most striking activation event going on during this process. The inhibition of WNK1 by WNK463 reduced the rate of corneal wound closure in both the hTEC and hCECs grown in monolayer compared with their respective negative controls. WNK463 also reduced phosphorylation of the WNK1 downstream targets SPAK/OSR1 in wounded hTECs. These in vitro results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and identified WNK1 as a kinase important to ensure proper wound healing of the cornea.

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Matrix regeneration agents improve wound healing in non-stressed human corneal epithelial cells

Cited by 6 publications

References 18 publications

Case Reports for Topical Treatment of Corneal Ulcers with a New Matrix Therapy Agent or RGTA® in Dogs

Case Reports for Topical Treatment of Corneal Ulcers with a New Matrix Therapy Agent or RGTA® in Dogs

Corneal Repair and Regeneration: Current Concepts and Future Directions

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

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