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

被引:5
作者
Bou Ghanem, Ghazi O. [1 ]
Koktysh, Dmitry [2 ]
Baratta, Robert O. [3 ]
Del Buono, Brian J. [3 ]
Schlumpf, Eric [3 ]
Wareham, Lauren K. [1 ]
Calkins, David J. [1 ]
机构
[1] Vanderbilt Univ, Med Ctr, Vanderbilt Eye Inst, Dept Ophthalmol & Visual Sci, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Vanderbilt Inst Nanoscale Sci & Engn, Nashville, TN 37212 USA
[3] Stuart Therapeut Inc, Stuart, FL 34994 USA
关键词
tissue biomechanics; extracellular matrix; extracellular matrix remodeling; collagen; collagen mimetic peptides; ATOMIC-FORCE MICROSCOPY; INTRAOCULAR-PRESSURE ELEVATION; EXTRACELLULAR-MATRIX; DEPRIVATION MYOPIA; GLOBAL PREVALENCE; LENS ELASTICITY; GLAUCOMA; RAT; EXPRESSION; STIFFNESS;
D O I
10.3390/ijms242317031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:12
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