Johns Hopkins University researchers have found new evidence that smoking and eye ageing are directly linked at a cellular level, revealing a far more complex picture than science has previously described. The findings appear in the Proceedings of the National Academy of Sciences. They could reshape how clinicians understand AMD, one of the world’s leading causes of blindness in older adults.

Age-related macular degeneration (AMD) is the leading cause of visual impairment in people aged 50 and over worldwide. Smokers are four times more likely to develop AMD than non-smokers. Yet the precise biological reasons have remained unclear. Until now.

How Smoking and Eye Ageing Connect Beyond Free Radicals

For years, scientists assumed cigarette smoke accelerated ageing mainly by releasing tissue-damaging molecules called free radicals. The new research tells a considerably more detailed story.

“Smoking is often assumed to accelerate ageing by releasing tissue-damaging molecules called free radicals,” said James T. Handa, principal investigator and chief of the retina division at the Wilmer Eye Institute at Johns Hopkins University. His team found that smoking also triggers epigenetic changes in the cells that protect the retina. Those changes carry far-reaching consequences for how cells function and cope with stress.

Epigenetic changes shift gene expression without altering a cell’s DNA sequence. Researchers found that cigarette smoke exposure reduced chromatin accessibility in retinal pigmented epithelial (RPE) cells. Chromatin controls which genes a cell can access and activate. Think of it as a gatekeeper for the cell’s entire operating manual.

When chromatin becomes less accessible, the cell loses much of its ability to adapt and survive.

What the Experiments Revealed About Cigarette Smoke and Macular Degeneration

Researchers compared RPE cells in mice at two life stages: one matching young adulthood in humans, one matching late middle age. Some mice received injections of cigarette smoke condensate over short periods. Others inhaled cigarette smoke daily for four months.

In both young and aged mice, short-term exposure produced clusters of dysfunctional RPE cells. These cells expressed fewer genes critical to normal function. They also struggled to regulate ageing-linked processes such as genomic instability, chromosomal deterioration, and mitochondrial disruption.

One finding stood out. A distinct subset of ageing-related genes switched on only in younger mice after smoke exposure, not in older ones. This pattern held across both short-term and long-term experiments. It suggests cigarette smoke and macular degeneration risk may vary depending on when in life exposure begins.

The team then examined RPE cells from four human donors: two without AMD who had never smoked, one without AMD who smoked, and one with early-stage AMD. Across human and mouse cells combined, 1,698 genes shifted in expression in a shared pattern. This strengthens the argument that these molecular changes are directly relevant to AMD in people.

Why This Research Matters

AMD affects an estimated 196 million people globally, a figure projected to reach 288 million by 2040. With populations ageing faster than ever, understanding what accelerates this disease carries real urgency.

“Knowing environmental stress can interfere with the eye’s ability to produce the genes needed to stay healthy, we now want to narrow down which changes are temporary and which are permanent,” Handa said. His team plans to investigate how sustained cigarette smoke exposure drives late-stage AMD progression.

The National Institutes of Health, the Research to Prevent Blindness Stein Innovation Award, and a BrightFocus Foundation macular degeneration research grant supported the study.

What this research makes plain is that smoking does not simply add stress to the eyes. It reprogrammes how eye cells age at a molecular level. For anyone thinking seriously about their long-term vision, that is a fact worth sitting with.

Source: futurity