Smoking after 50 can damage vision, study finds

A new study from Johns Hopkins Medicine sheds light on how smoking damages the eye at a molecular level, potentially accelerating the development of age-related macular degeneration (AMD), the leading cause of vision loss among adults 50 and older worldwide.

While researchers have long known that smokers face roughly four times the risk of developing AMD compared with non-smokers, the biological mechanisms behind that heightened risk have remained poorly understood. The new findings suggest cigarette smoke alters how key retinal cells function — not by changing their DNA sequence, but by modifying how genes are turned on and off.

The research, supported by the National Institutes of Health and published in the Proceedings of the National Academy of Sciences, focused on retinal pigmented epithelial (RPE) cells. These cells play a critical role in maintaining photoreceptors — the light-sensing cells that enable vision.

‘Accelerate aging’

“Smoking is often assumed to accelerate aging by releasing tissue-damaging molecules called free radicals,” said Dr. James T. Handa, principal investigator and chief of the retina division at the Wilmer Eye Institute. 

“Our study shows that smoking also causes epigenetic changes to RPE cells that have widespread effects on the eye and its ability to respond to environmental stress.”

To examine those changes, researchers compared RPE cells from young adult and late middle-aged mice — equivalent to 3-month-old and 12-month-old animals — following both short-term and prolonged exposure to cigarette smoke. Some mice received injections of cigarette smoke condensate and were studied days later, while others were exposed to daily smoke for four months.

Using advanced genetic sequencing techniques known as single-nucleus ATAC sequencing and single-nucleus RNA sequencing, the team analyzed how smoke exposure altered chromatin accessibility — a measure of how easily cells can access DNA to activate specific genes. 

Changes in chromatin structure can dramatically influence whether cells can adapt, function, and survive under stress.

Dysfunctional RPE cells

The results were significant. In both young and older mice, acute smoke exposure led to clusters of dysfunctional RPE cells. These cells showed reduced expression of genes essential to normal RPE function, along with decreased chromatin accessibility. They also showed lower activity in genes known as “hallmarks of aging” genes, which help regulate processes such as genomic stability, telomere maintenance, and mitochondrial function.

Many of these cellular changes mirror those observed in people with AMD, the researchers said.

However, the study also revealed age-related differences in how cells responded to smoke exposure. In young mice, a distinct subset of aging-related genes linked to mitochondrial function, protein stability, autophagy, inflammation, and metabolism became activated in dysfunctional cells. This response was absent in older mice.

“We saw the expression of aging genes linked to mitochondrial function, proteostasis, autophagy, inflammation, and metabolism increased only in the young, dysfunctional CSC-treated RPE cells,” Handa said.

Younger smokers are less affected

Using a technique known as TUNEL labeling to identify dying cells, researchers found that activation of these aging-related genes appeared to protect younger smoke-exposed cells. In contrast, older cells that failed to activate those genes were more likely to die.

To explore how the findings translate to humans, the team conducted additional experiments using donated RPE cells from two non-smokers without AMD, one smoker without AMD, and one person with early-stage AMD. They identified 1,698 genes with altered expression patterns shared between dysfunctional mouse and human RPE cells, suggesting common biological pathways may contribute to AMD development.

The researchers say the findings underscore how environmental stressors like cigarette smoke can interfere with the eye’s ability to maintain healthy gene expression patterns.