Effects of antiproteolytic agents on corneal epithelial viability and matrix metalloproteinase‐2 and metalloproteinase‐9 activity in alkali‐burned corneas of rats

Piso, Dunia Yisela Trujillo; Ribeiro, Alexandre Pinto; Silva, Miguel Ladino; Guimãraes, Patricia Jordão; Morales, Adriana; Martins, Bianca da Costa; Padua, Iván Ricardo Martínez; Renzo, Roberta; Andrade, Alexandre Lima de; Uscátegui, R. A. Ramírez; Laus, José Luiz

doi:10.1111/vop.12032

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…The model of iatrogenic induction of ulcers with filter paper was based on the experiments of [21] and [22]. Standardization of disk size and thickness and permanence on the corneal surface [23] minimized differences in depth, ensuring uniformity of the ulcers.…”

Section: Discussionmentioning

confidence: 99%

Use of Copaifera multijuga for acute corneal repair after chemical injury: A clinical, histopathological and toxicogenetic study

Dias

Jorge

Pereira

et al. 2017

Biomedicine & Pharmacotherapy

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Copaiba oil is widely used in medicine, but there are no reports regarding its application in ophthalmology. Therefore, the objective of this study was to evaluate the clinical, histopathological and toxicogenetic effects of eye drops containing 0.1 and 0.5% of Copaifera multijuga Hayne oil on superficial corneal ulcers induced with alkali in the left eye of rats. For histological analysis, the percent reduction in ulcers and thickness of the corneal epithelium and stroma were evaluated 48 and 72 h after ulcer induction. Additionally, neovascularization and polymorphonuclear infiltration were classified in the stroma. The bone marrow micronucleus test was used for toxicogenetic assessment. None of the animals exhibited clinical signs of immediate ocular discomfort after instillation and the eye drops were harmless to the ocular surface. There was a significant difference in percent ulcer reduction and corneal stroma thickness between animals treated with the C. multijuga eye drops and untreated animals with corneal injury and the negative control, respectively, suggesting a healing effect of the oleoresin. Analysis of the thickness of the corneal epithelium at the two time points showed that the eye drops formulated did not significantly reduce the damage caused by alkali. The same was observed for the treatments with the reference drugs. No difference in stromal neovascularization or inflammatory infiltration was observed between the treated groups. The toxicogenetic results revealed the absence of cytotoxicity and genotoxicity of the treatments. In conclusion, the C. multijuga eye drops did not cause damage to the ocular surface under the present experimental conditions and corneal epithelization was similar to the conventional treatments. These results indicate that eye drops containing C. multijuga oleoresin are a promising option for the treatment of superficial keratitis.

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Section: Discussionmentioning

confidence: 99%

Use of Copaifera multijuga for acute corneal repair after chemical injury: A clinical, histopathological and toxicogenetic study

Dias

Jorge

Pereira

et al. 2017

Biomedicine & Pharmacotherapy

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“…In addition, the investment required for pellet production is high. Alkaline cauterization remains the most widely used method for the induction of corneal angiogenesis, but its effectiveness may vary according to the protocol that is employed 6,7 . The lack of reproducibility represents a common problem, among studies involving models of angiogenesis induced by alkaline cauterization 10 .…”

Section: ■ Discussionmentioning

confidence: 99%

“…Many studies have focused on the elucidation of the mechanistic basis of angiogenesis, as well as on the development of drugs capable of blocking the progression of angiogenesis-dependent diseases, especially cancer 2,3,6 . Therefore, angiogenesis models are being utilized for in vitro applications, and in preclinical trials.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Due to its transparency and anatomical location, it facilitates the monitorization of vascular responses, and allows their quantification using biomicroscopy. Different protocols have been proposed for the experimental induction of angiogenesis in the cornea [6][7][8][9] . Twenty-four male rats (Rattus norvegicus, Wistar lineage), aged between 3 and 4 months, from the vivarium of the General Administration, UNESP, were used in this study.…”

Section: ■ Introductionmentioning

confidence: 99%

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Corneal angiogenesis based on different protocols of alkaline cauterization in murine models

et al. 2017

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Purpose: To establish and compare protocols of alkaline cauterization for inducing corneal angiogenesis in murine models. Methods: Twenty-four adult Wistar rats were distributed into four groups (G1, G2, G3, and G4). The right eye cornea from each rat was cauterized using filter paper (3 mm), soaked in a solution of silver and potassium nitrates (3:1). Cauterization times were 10 (G1 and G4), or 20 seconds (G2 and G3). Cauterized corneas were washed with Ringer's lactate solution. The filter paper was either removed before washing (G1 and G2), or kept on the corneas (G3 and G4). Corneas were photographed at multiple time points (2, 4, 6, 8, 11, 13, and 15 days after the procedure), and neovascularization parameters were assayed. Results: Neovascularization was observed in 66% of G1 corneas, and 100% of G2, G3, and G4 corneas. On day 15, G1 corneas showed smaller vascularized areas (12.63 ± 12.59%) compared to those in the G3 (41.95 ± 17.32%) and G4 (33 ± 11.74%) (P < 0.05) groups. Conclusions: The silver and potassium nitrate solution effectively induced corneal angiogenesis. The G2, G3, and G4 protocols showed excellent reproducibility, and induced vascularization in 100% of corneas.

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“…It is known that the activity of MMP-2 and MMP-9 can be regulated by TIMPs and other TIMP-like molecules, which contain similar sequences with the N-terminal sequence of the TIMPs. EDTA could interfere with the stability of MMPs and decreased the expression of MMP-2 and MMP-9 in alkali-burned rat corneas (Piso et al, 2014). Hence, we wish to provide a new approach to treating CNV by using specific inhibitors or agents to reduce the activity of MMP-2 and MMP-9 in the cornea.…”

Section: Some Other Drugsmentioning

confidence: 99%

Regulation of matrix metalloproteinases 2 and 9 in corneal neovascularization

Zhang

Wang

et al. 2020

Chem Biol Drug Des

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Corneal neovascularization (CNV), a pathological process of angiogenesis, can lead to serious consequences in the cornea. CNV is generally proved to associate with inflammation in the cornea closely, which is mainly elicited by the disruption of equilibrium between angiogenic and antiangiogenic factors. Angiogenic factors including vascular endothelial growth factors (VEGFs), basic fibroblast growth factors (bFGFs), and matrix metalloproteinases (MMPs) are vital factors in the formation of CNV. Especially VEGFs are convinced to be the core angiogenic factors in CNV, and MMPs are proved to exert dual effects on the process. Strikingly, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) are determined to play key roles in the formation of CNV, while the mechanism is still vague. In this review, the latest researches are reviewed to discuss the role of MMP-2 and MMP-9 in CNV, respectively, and some inhibitors of them are presented. We hope to provide a new direction of drug research for CNV. K E Y W O R D Scorneal neovascularization, matrix metalloproteinase 2, matrix metalloproteinase 9, vascular endothelial growth factor 486 | ZHANG et Al.How to cite this article: Zhang J, Wang S, He Y, Yao B, Zhang Y. Regulation of matrix metalloproteinases 2 and 9 in corneal neovascularization. Chem Biol Drug Des. 2020;95:485-492. https ://doi.

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Effects of antiproteolytic agents on corneal epithelial viability and matrix metalloproteinase‐2 and metalloproteinase‐9 activity in alkali‐burned corneas of rats

Cited by 11 publications

References 42 publications

Use of Copaifera multijuga for acute corneal repair after chemical injury: A clinical, histopathological and toxicogenetic study

Use of Copaifera multijuga for acute corneal repair after chemical injury: A clinical, histopathological and toxicogenetic study

Corneal angiogenesis based on different protocols of alkaline cauterization in murine models

Regulation of matrix metalloproteinases 2 and 9 in corneal neovascularization

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