Research Progress and Potential Applications of Spermidine in Ocular Diseases

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Jul 27

PMID 35890394

Authors

Wentao Han

Haoyu Li

Baihua Chen

Affiliations

Soon will be listed here.

Abstract

Spermidine, a natural polyamine, exists in almost all human tissues, exhibiting broad properties like anti-aging, autophagy induction, anti-inflammation, anti-oxidation, cell proliferation activation, and ion channel regulation. Considering that spermidine is already present in human nutrition, recent studies targeting supplementing exogenous sources of this polyamine appear feasible. The protective role of spermidine in various systems has been illuminated in the literature, while recent progress of spermidine administration in ocular diseases remains to be clarified. This study shows the current landscape of studies on spermidine and its potential to become a promising therapeutic agent to treat ocular diseases: glaucoma, optic nerve injury, age-related macular degeneration (AMD), cataracts, dry eye syndrome, and bacterial keratitis. It also has the potential to become a potent biomarker to predict keratoconus (KC), cataracts, uveitis, glaucoma, proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and retinopathy of prematurity (ROP). We also summarize the routes of administration and the effects of spermidine at different doses.

Citing Articles

Bee Pollen as a Source of Biopharmaceuticals for Neurodegeneration and Cancer Research: A Scoping Review and Translational Prospects.

Kacemi R, Campos M Molecules. 2025; 29(24).

PMID: 39769981 PMC: 11677910. DOI: 10.3390/molecules29245893.

Natural Autophagy Activators to Fight Age-Related Diseases.

Mundo Rivera V, Tlacuahuac Juarez J, Murillo Melo N, Leyva Garcia N, Magana J, Cordero Martinez J Cells. 2024; 13(19.

PMID: 39404375 PMC: 11476028. DOI: 10.3390/cells13191611.

A Bis(Acridino)-Crown Ether for Recognizing Oligoamines in Spermine Biosynthesis.

Kisfaludi P, Spatay S, Kreko M, Vezse P, Toth T, Huszthy P Molecules. 2024; 29(18).

PMID: 39339385 PMC: 11433836. DOI: 10.3390/molecules29184390.

Recommendations for nutritional supplements for dry eye disease: current advances.

Cong Y, Zhang Y, Han Y, Wu Y, Wang D, Zhang B Front Pharmacol. 2024; 15:1388787.

PMID: 38873421 PMC: 11169594. DOI: 10.3389/fphar.2024.1388787.

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF.

Jouyban K, Mohammad Jafari R, Charkhpour M, Rezaei H, Seyfinejad B, Manavi M Aesthetic Plast Surg. 2024; 48(17):3500-3509.

PMID: 38755497 DOI: 10.1007/s00266-024-04119-6.

References

Ni Y, Liu Y . New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases. Aging Dis. 2021; 12(8):1948-1963. PMC: 8612618. DOI: 10.14336/AD.2021.0603. View

Wickstrom K, Lundgren B, Torngren L, Ostberg C . Aqueous humor polyamines and alkaline phosphatase activity in endotoxin-induced uveitis: correlations to diverse leukocyte subsets. Ophthalmic Res. 1992; 24(3):175-80. DOI: 10.1159/000267165. View

Lentini A, Tabolacci C, Mattioli P, Provenzano B, Beninati S . Spermidine delays eye lens opacification in vitro by suppressing transglutaminase-catalyzed crystallin cross-linking. Protein J. 2011; 30(2):109-14. DOI: 10.1007/s10930-011-9311-7. View

Pan C, Ke C, Chen Q, Tao Y, Zha X, Zhang Y . Differential metabolic markers associated with primary open-angle glaucoma and cataract in human aqueous humor. BMC Ophthalmol. 2020; 20(1):183. PMC: 7203853. DOI: 10.1186/s12886-020-01452-7. View

Leidal A, Levine B, Debnath J . Autophagy and the cell biology of age-related disease. Nat Cell Biol. 2018; 20(12):1338-1348. DOI: 10.1038/s41556-018-0235-8. View

Lee G . The Balance of Th17 versus Treg Cells in Autoimmunity. Int J Mol Sci. 2018; 19(3). PMC: 5877591. DOI: 10.3390/ijms19030730. View

Zukerman R, Harris A, Verticchio Vercellin A, Siesky B, Pasquale L, Ciulla T . Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations. Genes (Basel). 2021; 12(1). PMC: 7823611. DOI: 10.3390/genes12010055. View

Jamerson E, Elhusseiny A, ElSheikh R, Eleiwa T, El Sayed Y . Role of Matrix Metalloproteinase 9 in Ocular Surface Disorders. Eye Contact Lens. 2020; 46 Suppl 2:S57-S63. DOI: 10.1097/ICL.0000000000000668. View

Kenney M, Nesburn A, Burgeson R, Butkowski R, Ljubimov A . Abnormalities of the extracellular matrix in keratoconus corneas. Cornea. 1997; 16(3):345-51. View

10.

Liu R, Li X, Ma H, Yang Q, Shang Q, Song L . Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy. Free Radic Biol Med. 2020; 161:339-350. DOI: 10.1016/j.freeradbiomed.2020.10.029. View

11.

Valentino T, Lukasiewicz P, Romano C . Immunocytochemical localization of polyamines in the tiger salamander retina. Brain Res. 1996; 713(1-2):278-85. DOI: 10.1016/0006-8993(95)01558-2. View

12.

Nicoletti R, Venza I, Ceci G, Visalli M, Teti D, Reibaldi A . Vitreous polyamines spermidine, putrescine, and spermine in human proliferative disorders of the retina. Br J Ophthalmol. 2003; 87(8):1038-42. PMC: 1771802. DOI: 10.1136/bjo.87.8.1038. View

13.

Mischiati C, Feriotto G, Tabolacci C, Domenici F, Melino S, Borromeo I . Polyamine Oxidase Is Involved in Spermidine Reduction of Transglutaminase Type 2-Catalyzed H-Crystallins Polymerization in Calcium-Induced Experimental Cataract. Int J Mol Sci. 2020; 21(15). PMC: 7432200. DOI: 10.3390/ijms21155427. View

14.

Moron B, Spalinger M, Kasper S, Atrott K, Frey-Wagner I, Fried M . Activation of protein tyrosine phosphatase non-receptor type 2 by spermidine exerts anti-inflammatory effects in human THP-1 monocytes and in a mouse model of acute colitis. PLoS One. 2013; 8(9):e73703. PMC: 3767590. DOI: 10.1371/journal.pone.0073703. View

15.

Ramot Y, Tiede S, Biro T, Abu Bakar M, Sugawara K, Philpott M . Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions. PLoS One. 2011; 6(7):e22564. PMC: 3144892. DOI: 10.1371/journal.pone.0022564. View

16.

Duncan G, Wormstone I . Calcium cell signalling and cataract: role of the endoplasmic reticulum. Eye (Lond). 2000; 13 ( Pt 3b):480-3. DOI: 10.1038/eye.1999.125. View

17.

Messerer J, Wrede C, Schipke J, Brandenberger C, Abdellatif M, Eisenberg T . Spermidine supplementation influences mitochondrial number and morphology in the heart of aged mice. J Anat. 2021; 242(1):91-101. PMC: 9773166. DOI: 10.1111/joa.13618. View

18.

Yang Q, Zheng C, Cao J, Cao G, Shou P, Lin L . Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages. Cell Death Differ. 2016; 23(11):1850-1861. PMC: 5071574. DOI: 10.1038/cdd.2016.71. View

19.

Wickstrom K . Polyamine and histopathological changes after unilateral endotoxin-induced uveitis and its contralateral effects. Acta Ophthalmol (Copenh). 1992; 70(4):506-14. DOI: 10.1111/j.1755-3768.1992.tb02121.x. View

20.

Wang Y, Devereux W, Woster P, Stewart T, Hacker A, Casero Jr R . Cloning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure. Cancer Res. 2001; 61(14):5370-3. View