Vascular Stress Contributes to Age-Associated Vision Loss
WASHINGTON, October 10, 2018 (Newswire.com) - An article published in Experimental Biology and Medicine (Volume 243, Issue 12, August, 2018 (http://journals.sagepub.com/doi/full/10.1177/1535370218794915) reports that vascular stress exacerbates age-associated vision loss. The study, led by Dr. Rajashekhar Gangaraju, in the Department of Ophthalmology and the Department of Anatomy and Neurobiology at the University of Tennessee Health Science Center in Memphis, TN, USA demonstrates that chronic activation of endothelial cells that line the surface of blood vessels promotes age-dependent losses in visual acuity in an animal model.
Vision loss adversely impacts quality of life. As people age, their risk for eye diseases and vision loss increases. During aging, some cells stop growing and functioning. These "senescent" cells can also have bystander effects on other cells and prevent them from performing their functions. Activation of the endothelial cells lining the small vessels in the eye results in a severe inflammatory response that includes release of the pro-inflammatory cytokine TNFα. TNFα is elevated in several retinal diseases, and Dr. Gangaraju's group has previously shown that TNFα results in premature senescence in endothelial cells. Nonetheless, the role of endothelial cells in age-associated senescence and its bystander effects on other retinal cells are not known.
In the current study, Dr. Gangaraju and colleagues used a novel mouse model that overexpresses TNFα in endothelial cells to assess the contribution of pre-mature senescence to age-induced visual deficits. In this model, 5 and 10-month-old mice exhibit relevant human equivalencies of mature adult (approximately 35-year-old) and middle-aged (approximately 50-year-old) patients. Both age groups exhibited visual deficits, and the loss of visual acuity was age-dependent. Markers of inflammation and endothelial cell activation/senescence also exhibited age-dependent increases. These findings suggest that endothelial cell senescence contributes to loss of vision and provide new insights regarding the pathophysiology of retinal diseases. Dr. Lenin, a co-author of the study, said that "future investigations are needed to delineate the downstream effects of senescence in this model." Dr. Gangaraju added that "a better understanding of endothelial cells in retinal diseases is indispensable for our understanding of the role of the neurovascular unit and may provide novel therapeutic targets to treat retinal disease."
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology & Medicine, said "Gangaraju and colleagues have utilized a mouse model that has constant endothelial activation to demonstrate age-dependent visual defects that correlated with ER stress and premature cell senescence. This study helps to elucidate the relationship between endothelial activation and loss of visual function."
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Source: Experimental Biology and Medicine