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Andrius Kazlauskas
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Title
Professor
Expertise
Retinopathy
Institution
Roche
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Developing approaches to protect from proliferative diabetic retinopathy
The goal of this proposal is to interrogate human samples (vitreous) to advance our understanding of the pathogenesis of diabetic retinopathy (DR). Vitreous is a depot of angiomodulators that govern the angiogenic status of retina vessels. We discovered that vitreous promotes regression of retinal neovessels, and the LPA (lysophosphatidic acid) was an essential element of this activity. This regression activity wanes as patients develop PDR, the stage of DR in which pathological neovessels accumulate in vitreous, even though the level of LPA persists. The goal of this proposal is to elucidate how PDR vitreous induces unresponsiveness to LPA, and to develop approaches to overcome it. We recently reported that diabetes (DM) activates the RSE (ROS, SFK, Erk) pathway in retinal endothelial cells and thereby antagonizes a signaling enzyme that is required for LPA-mediated regression. This proposal’s working hypothesis is built upon these previous findings and posits that PDR vitreous induces unresponsiveness to LPA by engaging the RSE pathway. The following 3 specific aims will test this hypothesis. 1. Determine whether PDR vitreous activates the RSE pathway. 2. Investigate whether pharmacologically targeting members of the RSE pathway overcomes PDR vitreous-induced non-responsiveness to LPA. 3. Same as Aim 2, except use a molecular approach.
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Developing approaches to protect from proliferative diabetic retinopathy (Kazlauskas, Andrius)
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Steering Committee
The DiaComp Steering Committee is the governing body of the consortium. The principle function of this committee is to guide the scientific direction of the consortium. This is accomplished by creating various subcommittees necessary to advance the scientific goals and providing guidance to the broader complications research community. Policies for the consortium are developed through consultation with the
External Evaluation Committee
Retinopathy
The DiaComp Retinopathy Committee has the principal function of furthering the mission of the consortium with regard to diabetic eye disease.
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Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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