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In Vivo Effect of RSH-12, a Novel Selective MMP-9 Inhibitor Peptide, in the Treatment of Experimentally Induced Dry Eye Model.
Curr Eye Res. 2020 Jun 21 [Online ahead of print]CE

Abstract

PURPOSE

To investigate the efficacy of RSH-12, a novel selective matrix metalloproteinase 9 (MMP-9) inhibitor peptide in rabbit models of dry eye syndrome (DES).

METHODS

In vitro toxicity of RSH-12 on cultured human corneal fibroblasts was investigated with MTT. Ocular toxicity of RSH-12 was investigated by clinical examinations, histology, and TUNEL assay. Experimental model of dry eye was induced by 1.0% atropine sulfate administration followed after 15 min by treatment with PBS, RSH-12, and Restasis in individual groups, three times a day for 7 days. In addition to performing Schirmer's test for evaluating basic tear secretion and tear break-up time test for investigating tear stability, the occurrence of superficial punctate keratopathy was also investigated in the study groups.

RESULTS

MTT assay demonstrated that RSH-12 was not toxic to human corneal fibroblasts in different concentrations. During the administration of atropine, TBUT values and tear volume were decreased in vehicle group while these indices improved significantly in groups treated with RSH-12 in a promising manner. RSH-12 increased the mean value of tear volume from 4.85 to 10.75 mm (P = .0001) and mean of TBUT values from 20.3 s to 34.5 s (P = .0001) compared with the vehicle. In contrast to the presence of severe superficial punctate keratopathy in the controls, no significant dotted staining was observed in the RSH-12 and Restasis groups.

CONCLUSIONS

These outcomes propose that RSH-12 has a therapeutic effect in the rabbit model of dry eye and might be a potential treatment for severe DES.

Authors+Show Affiliations

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University , Tehran, Iran.Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University , Tehran, Iran.Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran.Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran.Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University , Tehran, Iran.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32567381

Citation

Shoari, Alireza, et al. "In Vivo Effect of RSH-12, a Novel Selective MMP-9 Inhibitor Peptide, in the Treatment of Experimentally Induced Dry Eye Model." Current Eye Research, 2020, pp. 1-7.
Shoari A, Rasaee MJ, Rezaei Kanavi M, et al. In Vivo Effect of RSH-12, a Novel Selective MMP-9 Inhibitor Peptide, in the Treatment of Experimentally Induced Dry Eye Model. Curr Eye Res. 2020.
Shoari, A., Rasaee, M. J., Rezaei Kanavi, M., Afsar Aski, S., & Tooyserkani, R. (2020). In Vivo Effect of RSH-12, a Novel Selective MMP-9 Inhibitor Peptide, in the Treatment of Experimentally Induced Dry Eye Model. Current Eye Research, 1-7. https://doi.org/10.1080/02713683.2020.1782943
Shoari A, et al. In Vivo Effect of RSH-12, a Novel Selective MMP-9 Inhibitor Peptide, in the Treatment of Experimentally Induced Dry Eye Model. Curr Eye Res. 2020 Jun 21;1-7. PubMed PMID: 32567381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Vivo Effect of RSH-12, a Novel Selective MMP-9 Inhibitor Peptide, in the Treatment of Experimentally Induced Dry Eye Model. AU - Shoari,Alireza, AU - Rasaee,Mohammad Javad, AU - Rezaei Kanavi,Mozhgan, AU - Afsar Aski,Sasha, AU - Tooyserkani,Raheleh, Y1 - 2020/06/21/ PY - 2020/6/23/entrez KW - Matrix metalloproteinase 9 KW - RSH-12 KW - Schirmer’s test KW - dry eye syndrome KW - rabbits SP - 1 EP - 7 JF - Current eye research JO - Curr. Eye Res. N2 - PURPOSE: To investigate the efficacy of RSH-12, a novel selective matrix metalloproteinase 9 (MMP-9) inhibitor peptide in rabbit models of dry eye syndrome (DES). METHODS: In vitro toxicity of RSH-12 on cultured human corneal fibroblasts was investigated with MTT. Ocular toxicity of RSH-12 was investigated by clinical examinations, histology, and TUNEL assay. Experimental model of dry eye was induced by 1.0% atropine sulfate administration followed after 15 min by treatment with PBS, RSH-12, and Restasis in individual groups, three times a day for 7 days. In addition to performing Schirmer's test for evaluating basic tear secretion and tear break-up time test for investigating tear stability, the occurrence of superficial punctate keratopathy was also investigated in the study groups. RESULTS: MTT assay demonstrated that RSH-12 was not toxic to human corneal fibroblasts in different concentrations. During the administration of atropine, TBUT values and tear volume were decreased in vehicle group while these indices improved significantly in groups treated with RSH-12 in a promising manner. RSH-12 increased the mean value of tear volume from 4.85 to 10.75 mm (P = .0001) and mean of TBUT values from 20.3 s to 34.5 s (P = .0001) compared with the vehicle. In contrast to the presence of severe superficial punctate keratopathy in the controls, no significant dotted staining was observed in the RSH-12 and Restasis groups. CONCLUSIONS: These outcomes propose that RSH-12 has a therapeutic effect in the rabbit model of dry eye and might be a potential treatment for severe DES. SN - 1460-2202 UR - https://www.unboundmedicine.com/medline/citation/32567381/In_Vivo_Effect_of_RSH-12,_a_Novel_Selective_MMP-9_Inhibitor_Peptide,_in_the_Treatment_of_Experimentally_Induced_Dry_Eye_Model L2 - http://www.tandfonline.com/doi/full/10.1080/02713683.2020.1782943 DB - PRIME DP - Unbound Medicine ER -
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