Findings from a recent study published in Proceedings of the National Academy of Sciences show that cigarette smoke causes epigenetic changes in retinal pigment epithelial (RPE) cells in mice, producing a pattern of cellular degeneration that closely resembles what happens with normal aging.

The results point to a specific mechanism by which smoking may set the stage for age-related macular degeneration (AMD).

Give me some background first.

Some context: AMD is a leading cause of irreversible vision loss among people over 50 worldwide. Smokers face up to four times the risk of developing the disease compared to nonsmokers.

But here’s the gap: While the link between smoking and AMD risk is well established, the biological mechanism has remained unclear.

• The conventional assumption: That smoking drives damage primarily through oxidative stress, with free radicals directly injuring retinal tissue.

And with this new research?

This study tested a different angle: whether smoking also causes epigenetic changes to RPE cells that alter which genes get turned on or off, without changing the DNA sequence itself.

Now, talk about the study.

A team at Johns Hopkins’ Wilmer Eye Institute used single nuclear ATAC sequencing (snATAC-seq) and single nuclear RNA sequencing (snRNA-seq) to examine how RPE cells respond to cigarette smoke exposure at the epigenetic level.

The approach: snATAC-seq measures chromatin accessibility, meaning how physically open or closed a cell’s DNA packaging is. When chromatin is accessible, genes can be read and expressed. When it’s closed off, those genes go silent.

• Paired with snRNA-seq, the researchers could track both the structural changes and the resulting shifts in gene expression at single-cell resolution.

Who was included in the study?

Investigators injected cigarette smoke condensate (CSC) intravitreally into 3-month-old and 12-month-old mice, corresponding roughly to young adulthood and late middle age in humans.

• RPE/choroid tissue was collected at 3, 6, and 10 days post-injection.

A separate cohort of mice was exposed to cigarette smoke daily for 4 months to assess chronic exposure effects.

Human tissue was also examined: RPE cells from 4 donors were analyzed. Two had no AMD and did not smoke, one had no AMD but did smoke, and one had early AMD.

Read more: Does smoking age your eyes?

Source: eyes on glance

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