Wilmer Eye Institute at Johns Hopkins Medicine researchers identified molecular mechanisms by which smoking accelerates eye aging, offering new insight into how smoking contributes to age-related macular degeneration (AMD). The National Institutes of Health-funded study was published Jan. 16 in Proceedings of the National Academy of Sciences.
Here, we share the key findings and insights from James T. Handa, MD, chief of the Retina Division and the Robert Bond Welch, MD, professor of ophthalmology, Johns Hopkins University School of Medicine, from an interview with Insight Media.
Key Findings
The study examined retinal pigmented epithelial (RPE) cells from young and aged mice exposed to cigarette smoke condensate. RPE cells are essential for maintaining the health of photoreceptors required for vision. In young mice, smoke exposure increased aging-related gene activity and led to the formation of abnormal, dedifferentiated RPE clusters resembling those seen in aged, smoke-exposed mice.
Activation of certain aging genes appeared to protect young RPE cells from smoke-related stress, allowing those abnormal clusters to survive. In aged mice, however, continued smoke exposure led to RPE cell death.
“A key difference with smoke exposed young cells is that some genes that protect against aging were induced and protected against cell death while old cells were unable to provide a compensatory production of these protective genes, and thus, died from smoke stress,” says Dr. Handa, the study’s principal investigator. These genes are involved with mitochondria, proteostasis, and autophagy.
AMD and Patient Care
Molecular profiles from smoke-exposed RPE cells closely resembled those observed in human patients who smoke or have AMD. This suggests shared biological pathways across smoking exposure, aging, and disease.
Dr. Handa says the findings provide a new mechanistic explanation for how smoking contributes to the development of AMD. “This information strengthens that providers should emphasize to their patients the importance of smoking cessation,” he says. “This is especially true for young smokers who should stop before they lose their ability to compensate for the damage that smoking causes.”
Future Research
Researchers plan to further investigate how smoking- and age-related molecular changes contribute to AMD pathogenesis.
Dr. Handa says he wants to expand this type of work in a larger cohort of human donor eyes with spectrum of AMD disease stages. “By determining which genes (and functionally related clusters of genes) are abnormally produced, we can determine if they are interconnected or not,” he shares. “This understanding will determine if multiple drugs are needed to effectively treat AMD or if a single drug can neutralize multiple, interconnected disease-causing genes, and importantly, at what disease stage so treatment can be tailored for the specific AMD stage.”