Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD)

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Sep 28

PMID 34572131

Citations 33

Authors

Sonali Nashine

Affiliations

Soon will be listed here.

Abstract

Aging contributes to the risk of development of ocular diseases including, but not limited to, Age-related Macular Degeneration (AMD) that is a leading cause of blindness in the United States as well as worldwide. Retinal aging, that contributes to AMD pathogenesis, is characterized by accumulation of drusen deposits, alteration in the composition of Bruch's membrane and extracellular matrix, vascular inflammation and dysregulation, mitochondrial dysfunction, and accumulation of reactive oxygen species (ROS), and subsequent retinal pigment epithelium (RPE) cell senescence. Since there are limited options available for the prophylaxis and treatment of AMD, new therapeutic interventions are constantly being looked into to identify new therapeutic targets for AMD. This review article discusses the potential candidates for AMD therapy and their known mechanisms of cytoprotection in AMD. These target therapeutic candidates include APE/REF-1, MRZ-99030, Ciliary NeuroTrophic Factor (CNTF), RAP1 GTPase, Celecoxib, and SS-31/Elamipretide.

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References

Sardar Pasha S, Sishtla K, Sulaiman R, Park B, Shetty T, Shah F . Ref-1/APE1 Inhibition with Novel Small Molecules Blocks Ocular Neovascularization. J Pharmacol Exp Ther. 2018; 367(1):108-118. PMC: 7250474. DOI: 10.1124/jpet.118.248088. View

Chen M, Liu B, Gao Q, Zhuo Y, Ge J . Mitochondria-targeted peptide MTP-131 alleviates mitochondrial dysfunction and oxidative damage in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2011; 52(10):7027-37. DOI: 10.1167/iovs.11-7524. View

Schoenberger S, Kim S, Sheng J, Rezaei K, Lalezary M, Cherney E . Increased prostaglandin E2 (PGE2) levels in proliferative diabetic retinopathy, and correlation with VEGF and inflammatory cytokines. Invest Ophthalmol Vis Sci. 2012; 53(9):5906-11. DOI: 10.1167/iovs.12-10410. View

Bosch-Morell F, Villagrasa V, Ortega T, Acero N, Munoz-Mingarro D, Gonzalez-Rosende M . Medicinal plants and natural products as neuroprotective agents in age-related macular degeneration. Neural Regen Res. 2020; 15(12):2207-2216. PMC: 7749482. DOI: 10.4103/1673-5374.284978. View

Li Y, Yan J, De P, Chang H, Yamauchi A, Christopherson 2nd K . Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins. J Immunol. 2007; 179(12):8322-31. PMC: 2722108. DOI: 10.4049/jimmunol.179.12.8322. View

Ayalasomayajula S, Kompella U . Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol. 2005; 511(2-3):191-8. DOI: 10.1016/j.ejphar.2005.02.019. View

Qazi Y, Maddula S, Ambati B . Mediators of ocular angiogenesis. J Genet. 2010; 88(4):495-515. PMC: 3306772. DOI: 10.1007/s12041-009-0068-0. View

Duchniewicz M, Zemojtel T, Kolanczyk M, Grossmann S, Scheele J, Zwartkruis F . Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion. Mol Cell Biol. 2005; 26(2):643-53. PMC: 1346907. DOI: 10.1128/MCB.26.2.643-653.2006. View

Parsons C, Ruitenberg M, Freitag C, Sroka-Saidi K, Russ H, Rammes G . MRZ-99030 - A novel modulator of Aβ aggregation: I - Mechanism of action (MoA) underlying the potential neuroprotective treatment of Alzheimer's disease, glaucoma and age-related macular degeneration (AMD). Neuropharmacology. 2015; 92:158-69. DOI: 10.1016/j.neuropharm.2014.12.038. View

10.

Price L, Hajdo-Milasinovic A, Zhao J, Zwartkruis F, Collard J, Bos J . Rap1 regulates E-cadherin-mediated cell-cell adhesion. J Biol Chem. 2004; 279(34):35127-32. DOI: 10.1074/jbc.M404917200. View

11.

Nashine S, Chwa M, Kazemian M, Thaker K, Lu S, Nesburn A . Differential Expression of Complement Markers in Normal and AMD Transmitochondrial Cybrids. PLoS One. 2016; 11(8):e0159828. PMC: 4972370. DOI: 10.1371/journal.pone.0159828. View

12.

Sparrow J . Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics. Proc Natl Acad Sci U S A. 2016; 113(17):4564-9. PMC: 4855581. DOI: 10.1073/pnas.1600474113. View

13.

Sun Y, Cai N, Liu N . Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells. Cell Physiol Biochem. 2017; 44(4):1640-1650. DOI: 10.1159/000485764. View

14.

Wang H, Fotheringham L, Wittchen E, Hartnett M . Rap1 GTPase Inhibits Tumor Necrosis Factor-α-Induced Choroidal Endothelial Migration via NADPH Oxidase- and NF-κB-Dependent Activation of Rac1. Am J Pathol. 2015; 185(12):3316-25. PMC: 4729241. DOI: 10.1016/j.ajpath.2015.08.017. View

15.

Wu X, Pang Y, Zhang Z, Li X, Wang C, Lei Y . Mitochondria-targeted antioxidant peptide SS-31 mediates neuroprotection in a rat experimental glaucoma model. Acta Biochim Biophys Sin (Shanghai). 2019; 51(4):411-421. DOI: 10.1093/abbs/gmz020. View

16.

Rammes G, Parsons C . The Aβ aggregation modulator MRZ-99030 prevents and even reverses synaptotoxic effects of Aβ on LTP even following serial dilution to a 500:1 stoichiometric excess of Aβ, suggesting a beneficial prion-like seeding mechanism. Neuropharmacology. 2020; 179:108267. DOI: 10.1016/j.neuropharm.2020.108267. View

17.

Ding J, Johnson L, Herrmann R, Farsiu S, Smith S, Groelle M . Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration. Proc Natl Acad Sci U S A. 2011; 108(28):E279-87. PMC: 3136266. DOI: 10.1073/pnas.1100901108. View

18.

Sabate R, Estelrich J . Evidence of the existence of micelles in the fibrillogenesis of beta-amyloid peptide. J Phys Chem B. 2006; 109(21):11027-32. DOI: 10.1021/jp050716m. View

19.

Yan J, Li F, Ingram D, Quilliam L . Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and together with Rap1b controls human endothelial cell functions. Mol Cell Biol. 2008; 28(18):5803-10. PMC: 2546931. DOI: 10.1128/MCB.00393-08. View

20.

Ayalasomayajula S, Kompella U . Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular endothelial growth factor expression and vascular leakage in a streptozotocin-induced diabetic rat model. Eur J Pharmacol. 2002; 458(3):283-9. DOI: 10.1016/s0014-2999(02)02793-0. View