Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jun 23;12(13):1708.
doi: 10.3390/cells12131708.

Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment

Adnan H Khan  1   2 , Itay Chowers  3   4 , Andrew J Lotery  1   2
Affiliations
Review

Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment

Adnan H Khan et al. Cells. .

Abstract

Landmark genetic studies have revealed the effect of complement biology and its regulation on the pathogenesis of age-related macular degeneration (AMD). Limited phase 3 clinical trial data showing a benefit of complement inhibition in AMD raises the prospect of more complex mediators at play. Substantial evidence supports the role of para-inflammation in maintaining homeostasis in the retina and choroid. With increasing age, a decline in immune system regulation, known as immunosenescence, has been shown to alter the equilibrium maintained by para-inflammation. The altered equilibrium results in chronic, sterile inflammation with aging, termed 'inflammaging', including in the retina and choroid. The chronic inflammatory state in AMD is complex, with contributions from cells of the innate and adaptive branches of the immune system, sometimes with overlapping features, and the interaction of their secretory products with retinal cells such as microglia and retinal pigment epithelium (RPE), extracellular matrix and choroidal vascular endothelial cells. In this review, the chronic inflammatory state in AMD will be explored by immune cell type, with a discussion of factors that will need to be overcome in the development of curative therapies.

Keywords: age-related macular degeneration; immunosenescence; inflammaging; macular degeneration; senolytics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wong W.L., Su X., Li X., Cheung C.M., Klein R., Cheng C.Y., Wong T.Y. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis. Lancet Glob. Health. 2014;2:e106–e116. doi: 10.1016/S2214-109X(13)70145-1. - DOI - PubMed
    1. Khandhadia S., Cherry J., Lotery A.J. Age-related macular degeneration. Adv. Exp. Med. Biol. 2012;724:15–36. doi: 10.1007/978-1-4614-0653-2_2. - DOI - PubMed
    1. Mitchell P., Liew G., Gopinath B., Wong T.Y. Age-related macular degeneration. Lancet. 2018;392:1147–1159. doi: 10.1016/S0140-6736(18)31550-2. - DOI - PubMed
    1. Keenan T.D., Vitale S., Agron E., Domalpally A., Antoszyk A.N., Elman M.J., Clemons T.E., Chew E.Y., Age-Related Eye Disease Study 2 Research G. Visual Acuity Outcomes after Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report Number 19. Ophthalmol. Retina. 2020;4:3–12. doi: 10.1016/j.oret.2019.06.001. - DOI - PMC - PubMed
    1. Ezzat M.K., Hann C.R., Vuk-Pavlovic S., Pulido J.S. Immune cells in the human choroid. Br. J. Ophthalmol. 2008;92:976–980. doi: 10.1136/bjo.2007.129742. - DOI - PubMed

Publication types