Bushra Zaman
The Role of Clusterin in Ischemic Retinopathies
Abstract
Retinal ischemia is a hallmark of potentially blinding eye diseases such as diabetic retinopathy and central retinal artery occlusion (CRAO). Available treatments do not halt disease progression. Using unbiased proteomic analysis, we have recently identified the glycoprotein clusterin (CLU) to be downregulated in aqueous humor (AH) from CRAO patients. Preliminary data showed that CLU administration is neuroprotective in a mouse model of retinal ischemia. Our lab has recently found a protective role of macrophages lacking the enzyme histone deacetylase 3 (HDAC3) in retinal ischemic injury via enhanced clearance of dead cells. RNA-sequencing showed CLU upregulation in macrophages lacking HDAC3. Here, we will investigate the cross-talk between CLU and HDAC3 in retinal neurovascular protection and the role of the CLU receptor, TREM2, in retinal ischemia. This proposal will involve extensive training on in vivo, in vitro, and ex vivo techniques related to ischemic retinopathy.
This fellowship serves as a reminder to myself that scientists can accomplish remarkable things with the right support. As such, I am incredibly grateful to the PhRMA Foundation for supporting my research! I am excited to see how my project translates from the bench to the bedside in the future.