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Julia Adeloef; The role of PA28αβ in cataract. Invest. Ophthalmol. Vis. Sci. 2016;57(12):736.
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© ARVO (1962-2015); The Authors (2016-present)
Cataract is the main cause of blindness globally today and the disease is characterized by lens opacification due to protein aggregates. Oxidative stress is a known trigger for protein aggregation in many different proteinopathies such as cataract, Alzheimer’s and Parkinson’s disease. Proteasome activator PA28αβ is expressed under immunological and oxidative stress conditions. Previous research shows that PA28αβ is involved in MHC class I antigen presentation. This function is excessive in the immune privileged lens tissue which interestingly accentuates a probability of alternative functions of PA28αβ. Recently published data show the potentially protective role for PA28αβ against oxidative stress and in this study, the presence and expression of PA28αβ in native human lens epithelial cells are investigated. The aim of the study is to understand the function of PA28αβ, if it can protect lens cells against oxidative stress and if PA28αβ potentially acts protectively against cataract.
Western Blot was performed on cultured human lens epithelial cells (HLECs) from cataract patients for detection of PA28α and Pa28β presence in lenses. HLECs were also investigated under oxidative stress by one hour exposure to 100 or 1000 µM H2O2. Expression of PA28α and Pa28β are investigated by Western Blot at different times after exposure.Transgenic PA28α OE C57BL/6 mice injected with low dose streptozotocin develop diabetes induced cataract. Intact lenses and mice lens epithelial cells from these mice are investigated in relation to disease incidence, levels of oxidative stress and protein damage.
Western blots verify the existence of PA28α and PA28β in HLECs. Transgenic mice has been confirmed to have an overexpression of PA28α in lens epithelial cells. Ongoing experiments analyze the PA28α and PA28β expression in HLECs under oxidative stress conditions and the expression in lenses of induced cataract mice.
Existence of PA28αβ in lens epithelial cells indicates importance of proteasome regulation and unknown function for PA28αβ. Further investigations will augment the understanding for additional roles of PA28αβ, particularly under oxidative stress, and if induction of PA28αβ may serve effectively in preventing and/or treating cataract.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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