Dataset Information

Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.

ABSTRACT:

Purpose

Previously, we found norepinephrine (NE) could affect the corneal epithelial integrity, herein we investigated the feasibility and safety of NE serving as a chemical enhancer to promote corneal penetration of riboflavin during transepithelial corneal crosslinking (CXL).

Methods

The dosage of NE that could promote riboflavin diffusion through the healthy epithelial barrier without inducing epithelial damage in C57BL/6 mice was determined. The safety of NE treatment was confirmed by morphological and histological examinations of the whole cornea. The efficacy of NE in promoting riboflavin penetration was verified by slit lamp and scanning electron microscope (SEM), and corneal biomechanical measurement after CXL. To better fit the clinical scenario, increased NE dosage and shortened riboflavin infiltration time were further evaluated.

Results

The lowest dosage of NE (1 mg/mL) that facilitated transepithelial riboflavin permeation was 2 µL. No visible corneal structure alteration was observed after NE treatment. SEM indicated dissociation of intercellular junctions among corneal epithelial cells. Homogenous distribution of riboflavin throughout corneal stroma was observed. NE-treated corneas reached comparable biomechanical properties after CXL, including stress-relaxation curve and elastic modulus, with corneas treated with the commercially available transepithelial drug Peschke TE. To better fit the clinical scenario, increasing NE up to 5.5 µL helped riboflavin infiltrate the corneal stroma within 30 minutes. After CXL with 9 mW/cm2 ultraviolet-A (UVA) for 2.5 minutes, the cornea showed significantly enhanced corneal biomechanical properties with undisturbed corneal endothelium.

Conclusions

NE serves as an effective enhancer in increasing riboflavin diffusion with limited impairment on corneal epithelium and has great potential for clinical application.

Translation relevance

NE serves as an effective enhancer for riboflavin penetration and clinical transepithelial CXL.

SUBMITTER: Liu G

PROVIDER: S-EPMC9932548 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.

Liu Guoying G Li Tan T Qi Benxiang B Gong Ganyu G Guo Tengyou T Zhou Qingjun Q Jhanji Vishal V Zhang Bi Ning BN Du Xianli X

Translational vision science & technology 20230201 2

<h4>Purpose</h4>Previously, we found norepinephrine (NE) could affect the corneal epithelial integrity, herein we investigated the feasibility and safety of NE serving as a chemical enhancer to promote corneal penetration of riboflavin during transepithelial corneal crosslinking (CXL).<h4>Methods</h4>The dosage of NE that could promote riboflavin diffusion through the healthy epithelial barrier without inducing epithelial damage in C57BL/6 mice was determined. The safety of NE treatment was conf ...[more]

PMID: 36786745

Similar Datasets

Project description:Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution. At UVA doses higher than a threshold level of 0.54 J/cm2, resistance to enzymatic digestion increased relative to that in non-irradiated corneas. Based on the theoretical threshold CXL dose, a CXL regimen was established in which the UVA tissue irradiance was 9 mW/cm2, which was delivered at doses of either 2.16, 2.7 or 3.24 J/cm2. Their dose dependent effects were evaluated on ocular surface morphological integrity, keratocyte apoptotic frequency, tissue thickness and endothelial cell layer density. Doses of 2.16 and 2.7 J/cm2 transiently decreased normal corneal transparency and increased thickness. These effects were fully reversed after 14 days. In contrast, 3.24 J/cm2 had more irreversible side effects. Three days after treatment, apoptotic frequency in the CXL-2.16 group was lower than that at higher doses. Endothelial cell losses remained evident only in the CXL-3.24 group at 42 days posttreatment. Stromal fiber thickening was evident in all the CXL-treated groups. We determined both the threshold UVA dose using the high-intensity CXL procedure and identified an effective dose range that provides optimal CXL with minimal transient side effects in the rat cornea. These results may help to provide insight into how to improve the CXL outcome in patients afflicted with a severe corneal thinning disease.

Dataset Information

Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.

Purpose

Methods

Results

Conclusions

Translation relevance

Publications

Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.

Similar Datasets

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