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Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models.
Int J Mol Sci. 2022 Mar 08; 23(6)IJ

Abstract

Vision loss through the degeneration of retinal ganglion cell (RGC) axons occurs in both chronic and acute conditions that target the optic nerve. These include glaucoma, in which sensitivity to intraocular pressure (IOP) causes early RGC axonal dysfunction, and optic nerve trauma, which causes rapid axon degeneration from the site of injury. In each case, degeneration is irreversible, necessitating new therapeutics that protect, repair, and regenerate RGC axons. Recently, we demonstrated the reparative capacity of using collagen mimetic peptides (CMPs) to heal fragmented collagen in the neuronal extracellular milieu. This was an important step in the development of neuronal-based therapies since neurodegeneration involves matrix metalloproteinase (MMP)-mediated remodeling of the collagen-rich environment in which neurons and their axons exist. We found that intraocular delivery of a CMP comprising single-strand fractions of triple helix human type I collagen prevented early RGC axon dysfunction in an inducible glaucoma model. Additionally, CMPs also promoted neurite outgrowth from dorsal root ganglia, challenged in vitro by partial digestion of collagen. Here, we compared the ability of a CMP sequence to protect RGC axons in both inducible glaucoma and optic nerve crush. A three-week +40% elevation in IOP caused a 67% degradation in anterograde transport to the superior colliculus, the primary retinal projection target in rodents. We found that a single intravitreal injection of CMP during the period of IOP elevation significantly reduced this degradation. The same CMP delivered shortly after optic nerve crush promoted significant axonal recovery during the two-week period following injury. Together, these findings support a novel protective and reparative role for the use of CMPs in both chronic and acute conditions affecting the survival of RGC axons in the optic projection to the brain.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, AA7103 MCN/VUIIS, 1161 21st Ave. S., Nashville, TN 37232, USA.Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, AA7103 MCN/VUIIS, 1161 21st Ave. S., Nashville, TN 37232, USA.Stuart Therapeutics, Inc., 411 SE Osceola St., Suite 203, Stuart, FL 34994, USA.Stuart Therapeutics, Inc., 411 SE Osceola St., Suite 203, Stuart, FL 34994, USA.Stuart Therapeutics, Inc., 411 SE Osceola St., Suite 203, Stuart, FL 34994, USA.Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, AA7103 MCN/VUIIS, 1161 21st Ave. S., Nashville, TN 37232, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35328332

Citation

Ribeiro, Marcio, et al. "Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models." International Journal of Molecular Sciences, vol. 23, no. 6, 2022.
Ribeiro M, McGrady NR, Baratta RO, et al. Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models. Int J Mol Sci. 2022;23(6).
Ribeiro, M., McGrady, N. R., Baratta, R. O., Del Buono, B. J., Schlumpf, E., & Calkins, D. J. (2022). Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models. International Journal of Molecular Sciences, 23(6). https://doi.org/10.3390/ijms23062911
Ribeiro M, et al. Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models. Int J Mol Sci. 2022 Mar 8;23(6) PubMed PMID: 35328332.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intraocular Delivery of a Collagen Mimetic Peptide Repairs Retinal Ganglion Cell Axons in Chronic and Acute Injury Models. AU - Ribeiro,Marcio, AU - McGrady,Nolan R, AU - Baratta,Robert O, AU - Del Buono,Brian J, AU - Schlumpf,Eric, AU - Calkins,David J, Y1 - 2022/03/08/ PY - 2022/01/28/received PY - 2022/03/01/revised PY - 2022/03/02/accepted PY - 2022/3/25/entrez PY - 2022/3/26/pubmed PY - 2022/4/9/medline KW - collagen mimetic peptides KW - collagen reparative KW - extracellular matrix KW - glaucoma KW - neuroprotection KW - optic nerve crush KW - optic neuropathy JF - International journal of molecular sciences JO - Int J Mol Sci VL - 23 IS - 6 N2 - Vision loss through the degeneration of retinal ganglion cell (RGC) axons occurs in both chronic and acute conditions that target the optic nerve. These include glaucoma, in which sensitivity to intraocular pressure (IOP) causes early RGC axonal dysfunction, and optic nerve trauma, which causes rapid axon degeneration from the site of injury. In each case, degeneration is irreversible, necessitating new therapeutics that protect, repair, and regenerate RGC axons. Recently, we demonstrated the reparative capacity of using collagen mimetic peptides (CMPs) to heal fragmented collagen in the neuronal extracellular milieu. This was an important step in the development of neuronal-based therapies since neurodegeneration involves matrix metalloproteinase (MMP)-mediated remodeling of the collagen-rich environment in which neurons and their axons exist. We found that intraocular delivery of a CMP comprising single-strand fractions of triple helix human type I collagen prevented early RGC axon dysfunction in an inducible glaucoma model. Additionally, CMPs also promoted neurite outgrowth from dorsal root ganglia, challenged in vitro by partial digestion of collagen. Here, we compared the ability of a CMP sequence to protect RGC axons in both inducible glaucoma and optic nerve crush. A three-week +40% elevation in IOP caused a 67% degradation in anterograde transport to the superior colliculus, the primary retinal projection target in rodents. We found that a single intravitreal injection of CMP during the period of IOP elevation significantly reduced this degradation. The same CMP delivered shortly after optic nerve crush promoted significant axonal recovery during the two-week period following injury. Together, these findings support a novel protective and reparative role for the use of CMPs in both chronic and acute conditions affecting the survival of RGC axons in the optic projection to the brain. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/35328332/Intraocular_Delivery_of_a_Collagen_Mimetic_Peptide_Repairs_Retinal_Ganglion_Cell_Axons_in_Chronic_and_Acute_Injury_Models_ DB - PRIME DP - Unbound Medicine ER -