Andrius Kazlauskas

Personal Information
Title Professor
Expertise Retinopathy
Institution Roche
Data Summary
Grants/SubContracts 1
Progress Reports 1
Publications 0
Protocols 0
Committees 2


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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