Collagen Mimetic Peptides Promote Repair of MMP-1-Damaged Collagen in the Rodent Sclera and Optic Nerve Head

Author:

Bou Ghanem Ghazi O.1ORCID,Koktysh Dmitry2,Baratta Robert O.3ORCID,Del Buono Brian J.3,Schlumpf Eric3ORCID,Wareham Lauren K.1ORCID,Calkins David J.1ORCID

Affiliation:

1. Vanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA

2. Vanderbilt Institute of Nanoscale Science and Engineering, Vanderbilt University, Nashville, TN 37212, USA

3. Stuart Therapeutics, Inc., Stuart, FL 34994, USA

Abstract

The structural and biomechanical properties of collagen-rich ocular tissues, such as the sclera, are integral to ocular function. The degradation of collagen in such tissues is associated with debilitating ophthalmic diseases such as glaucoma and myopia, which often lead to visual impairment. Collagen mimetic peptides (CMPs) have emerged as an effective treatment to repair damaged collagen in tissues of the optic projection, such as the retina and optic nerve. In this study, we used atomic force microscopy (AFM) to assess the potential of CMPs in restoring tissue stiffness in the optic nerve head (ONH), including the peripapillary sclera (PPS) and the glial lamina. Using rat ONH tissue sections, we induced collagen damage with MMP-1, followed by treatment with CMP-3 or vehicle. MMP-1 significantly reduced the Young’s modulus of both the PPS and the glial lamina, indicating tissue softening. Subsequent CMP-3 treatment partially restored tissue stiffness in both the PPS and the glial lamina. Immunohistochemical analyses revealed reduced collagen fragmentation after MMP-1 digestion in CMP-3-treated tissues compared to vehicle controls. In summary, these results demonstrate the potential of CMPs to restore collagen stiffness and structure in ONH tissues following enzymatic damage. CMPs may offer a promising therapeutic avenue for preserving vision in ocular disorders involving collagen remodeling and degradation.

Funder

Stuart Therapeutics, Inc.

Vanderbilt Institute of Nanoscale Science and Engineering

VINSE pilot grant

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference64 articles.

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4. The epidemics of myopia: Aetiology and prevention;Morgan;Prog. Retin. Eye Res.,2018

5. Myopia;Morgan;Lancet,2012

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