Generic placeholder image

Current Aging Science


ISSN (Print): 1874-6098
ISSN (Online): 1874-6128


The Implication of Alu cDNA in the Pathogenesis of ARMD

Author(s): Ali Nouraeinejad*

Volume 16, Issue 3, 2023

Published on: 21 June, 2023

Page: [168 - 169] Pages: 2

DOI: 10.2174/1874609816666230530095410


Age-related macular degeneration (ARMD or AMD) is a progressive, sight-threatening disease. The pathogenesis of ARMD is complex, involving many factors, such as metabolic, functional, genetic, and environmental factors. Recently, long interspersed nuclear element-1 (L1)– mediated reverse transcription (RT) of Alu RNA into cytoplasmic Alu complementary DNA (cDNA) has been associated with retinal pigment epithelium (RPE) destruction. These findings provide a strong input for a new direction in the management of ARMD, as certain human immunodeficiency virus (HIV) drugs, such as nucleoside reverse transcriptase inhibitors (NRTIs), were found to suppress inflammation and protect cells of the retina.

Keywords: Age-related macular degeneration, Alu complementary DNA, inflammasome activation, retinal pigment epithelium, nucleoside reverse transcriptase inhibitors, HIV.

Fukuda S, Varshney A, Fowler BJ, et al. Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration. Proc Natl Acad Sci 2021; 118(6): e2022751118.
[] [PMID: 33526699]
Fukuda S, Narendran S, Varshney A, et al. Alu complementary DNA is enriched in atrophic macular degeneration and triggers retinal pigmented epithelium toxicity via cytosolic innate immunity. Sci Adv 2021; 7(40): eabj3658.
[] [PMID: 34586848]
Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy. Pharmacol Rep 2006; 58(3): 353-63.
[PMID: 16845209]
Heinrich MJ, Purcell CA, Pruijssers AJ, et al. Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis. J Autoimmun 2019; 100: 40-51.
[] [PMID: 30826177]
Ambati J, Magagnoli J, Leung H, et al. Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development. Nat Commun 2020; 11(1): 4737.
Narendran S, Pereira F, Yerramothu P, et al. Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-β induced retinal pigmented epithelium degeneration. Signal Transduct Target Ther 2021; 6(1): 149.
[] [PMID: 33850097]
Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J. Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest 2006; 116(2): 378-85.
[] [PMID: 16453022]
Isas JM, Luibl V, Johnson LV, et al. Soluble and mature amyloid fibrils in drusen deposits. Invest Ophthalmol Vis Sci 2010; 51(3): 1304-10.
[] [PMID: 19892876]
Ohno-Matsui K. Parallel findings in age-related macular degeneration and Alzheimer’s disease. Prog Retin Eye Res 2011; 30(4): 217-38.
[] [PMID: 21440663]
Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron 2012; 75(1): 26-39.
[] [PMID: 22794258]
Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat Immunol 2008; 9(8): 857-65.
[] [PMID: 18604209]
Nakanishi A, Kaneko N, Takeda H, et al. Amyloid β directly interacts with NLRP3 to initiate inflammasome activation: Identification of an intrinsic NLRP3 ligand in a cell-free system. Inflamm Regen 2018; 38(1): 27.
[] [PMID: 30459926]
Fekete C, Vastagh C, Dénes Á, et al. Chronic amyloid β oligomer infusion evokes sustained inflammation and microglial changes in the rat hippocampus via NLRP3. Neuroscience 2019; 405: 35-46.
[] [PMID: 29522854]
Tarallo V, Hirano Y, Gelfand BD, et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 2012; 149(4): 847-59.
[] [PMID: 22541070]
Tseng WA, Thein T, Kinnunen K, et al. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: Implications for age-related macular degeneration. Invest Ophthalmol Vis Sci 2013; 54(1): 110-20.
[] [PMID: 23221073]
Kerur N, Fukuda S, Banerjee D, et al. cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. Nat Med 2018; 24(1): 50-61.
[] [PMID: 29176737]
Kaarniranta K, Tokarz P, Koskela A, Paterno J, Blasiak J. Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration. Cell Biol Toxicol 2017; 33(2): 113-28.
[] [PMID: 27900566]
Zhang ZY, Bao XL, Cong YY, Fan B, Li GY. Autophagy in age-related macular degeneration: A regulatory mechanism of oxidative stress. Oxid Med Cell Longev 2020; 2020: 1-13.
[] [PMID: 32831993]
Hyttinen JMT, Blasiak J, Felszeghy S, Kaarniranta K. MicroRNAs in the regulation of autophagy and their possible use in age-related macular degeneration therapy. Ageing Res Rev 2021; 67: 101260.
[] [PMID: 33516915]

© 2023 Bentham Science Publishers | Privacy Policy