Smoking may speed eye aging and lead to AMD ^{CEFR B2}

A new study published in the Proceedings of the National Academy of Sciences explains how cigarette smoke can accelerate aging in the eye and help cause age-related macular degeneration (AMD). AMD is the leading worldwide cause of visual impairment and blindness among people age 50 and older, and people who smoke are four times more likely to develop AMD than non-smokers.

The researchers used experiments in mice and tests of donated human retinal pigmented epithelial (RPE) cells. They compared RPE cells from 3-month and 12-month mice after both acute and chronic cigarette smoke exposure, noting that those mouse ages roughly correspond to young adulthood and late middle age in humans. The team injected cigarette smoke condensate and sampled cells three, six, and ten days later, and they also examined mice exposed to smoke daily for four months. Using genetic sequencing, they identified dysfunctional RPE clusters and measured chromatin accessibility. Chromatin is the condensed DNA–RNA–protein structure that determines which genes are turned on or off.

Acute exposure produced dysfunctional RPE clusters with lower expression of core RPE function genes, reduced chromatin accessibility, and decreased expression of so-called "hallmarks of aging" genes. These hallmarks include processes such as genomic instability, shortening of chromosome ends (telomeres), and disruption of mitochondria. The molecular changes mirrored characteristics seen in human AMD and a distinct subset of aging genes appeared only in dysfunctional cells of young mice. Similar differences were seen after four months of daily smoke exposure.

In tests of donated human RPE cells—from two people without AMD who did not smoke, one person without AMD who smoked, and one person with early AMD—the team identified 1,698 genes with shared changes between dysfunctional human and mouse RPE cells. The researchers say these shared genes may be relevant to AMD development and progression. Handa said the next steps are to determine which changes are temporary and which are permanent and to study how age and continuous smoke exposure contribute to eye damage and comorbidities in late-stage AMD. The study was supported by the National Institutes of Health, the Research to Prevent Blindness Stein Innovation Award, and a BrightFocus Foundation macular degeneration research grant. Handa is on the scientific advisory boards for Character Biosciences, Cirrus Pharmaceuticals, and Seeing Medicines.