Abstract
Purpose :
Our study examines the hypothesis that smoking significantly alters the expression of genes involved in intracellular calcium signaling during the development and progression of age-related macular degeneration (AMD).
Methods :
We utilized a subset of the Eye Genotype Expression (EyeGEx) database, which includes transcriptional profiles from 453 postmortem retinal samples and covers over 13,662 protein-coding and 1,462 non-coding genes. Advanced statistical methods, such as multivariate analysis and correlation techniques, were employed to analyze changes in gene transcription in relation to cigarette smoking while controlling for other critical factors like hypertension and age.
Results :
Smoking is associated with notable changes in the expression of specific genes that control intracellular calcium signaling suggesting a potential new mechanism by which smoking might exacerbate AMD progression, considering the established roles of these genes in the function of nerve cells and disease pathogenesis. We observed expression changes in hypertensive patients, and based on age indicating the critical importance of these biological variables in AMD. Moreover, significant correlations were identified between the severity of AMD, as gauged by the Minnesota Grading System, and changes in gene expression related to neuronal calcium signaling. These genetic factors influencing the severity of AMD reveal the complex interaction between genetic elements and environmental factors.
Conclusions :
Our research highlights the significant impact of smoking on the expression of genes that control intracellular calcium signaling related to AMD. This discovery sheds light on new genetic factors potentially involved in AMD, demonstrating the need to account for altered gene expression in response to environmental factors like smoking in studying and treating the condition. Our findings contribute to the knowledge on mechanisms underlying AMD development and open new avenues for creating personalized treatments that consider unique genetic and environmental characteristics in different patient groups.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.