Abstract
Degeneration of macular photoreceptors is a prominent characteristic of age-related macular degeneration (AMD) which leads to devastating and irreversible vision loss in the elderly population. In this exploratory study, the contribution of environmental factors on the progression of AMD pathology by probing the expression of candidate proteins was analyzed. Four hundred and sixty four participants were recruited in the study comprising of AMD (n = 277) and controls (n = 187). Genetics related data was analyzed to demonstrate the activities of daily living (ADL) by using regression analysis and statistical modeling, including contrast estimate, multinomial regression analysis in AMD progression. Regression analysis revealed contribution of smoking, alcohol, and sleeping hours on AMD by altered expression of IER-3, HTRA1, B3GALTL, LIPC and TIMP3 as compared to normal levels. Contrast estimate supports the gender polarization phenomenon in AMD by significant decreased expression of SLC16A8 and LIPC in control population which was found to be unaltered in AMD patients. The smoking, food habits and duration of night sleeping hours also contributed in AMD progression as evident from multinomial regression analysis. Predicted model (prediction estimate = 86.7%) also indicated the crucial role of night sleeping hours along with the decreased expression of TIMP-3, IER3 and SLC16A8. Results revealed an unambiguous role of environmental factors in AMD progression mediated by various regulatory proteins which might result in intermittent AMD phenotypes and possibly influence the outcome of anti-VEGF treatment.
Highlights
Most of the degenerative diseases (e.g. age-related macular degeneration (AMD) and Alzheimer’s disease) have shown complex phenotypes based on both gene-environment interactions which have propensity to alter the cellular functions by gene expression changes [1, 2]
We report that there is an alteration in expressions of HtrA Serine Peptidase 1 (HTRA1), Tissue inhibitor of metalloproteinase-3 (TIMP-3) and Immediate Early Response 3 (IER-3) in sleep deprived individuals or AMD patients with increase in sleep duration, prompting further research [24, 25]
Activities of daily living (ADL) of the participants were analyzed to examine if association existed between AMD and these variables
Summary
Most of the degenerative diseases (e.g. AMD and Alzheimer’s disease) have shown complex phenotypes based on both gene-environment interactions which have propensity to alter the cellular functions by gene expression changes [1, 2]. AMD is characterized by degenerative changes in macular photoreceptors and vision impairment in elderly. It is associated with various environmental factors and 52 independent genetic loci [3]. Most of reported AMD alleles have not been probed for interaction with environmental factors rendering the genetic studies of AMD an incomplete and unimpactful analysis.
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