Research Projects

Retinopathy is a sight-threatening complication of diabetes, often initiated too late after significant neurodegeneration has occurred in retinal tissue. The researchers aim to identify the core molecular mechanisms governing neuritogenesis in adult retinal neurons and explore how these pathways are affected by hyperglycemia in vitro and diabetes in vivo. They hypothesize that a transmembrane protein called Caspr1 negatively regulates neuritogenesis in adult retinal neurons, and will test the hypothesis that Caspr1 is transcriptionally regulated by glucose-sensitive transcription factors. They will also investigate downstream signaling through actin-modulating proteins such as phosphorylated VASP and small GTPases. The researchers will use a retinal neuronal cell line (661W), retinal explants cultured in varied glycemic conditions with Caspr1 knocked out, and an in vivo mouse model of diabetic retinopathy to study neuritogenesis in primary neurons isolated from adult retina. They will also use post-mortem human retinal tissue to validate their findings. The researchers propose to conduct studies using mature, post-mitotic neurons isolated from adult retina, in contrast to traditional studies using embryonic tissue or neurons isolated from young pups. This will help identify core molecular pathways governing neuritogenesis in adult retinal neurons under altered metabolic conditions, which is the first step towards developing reliable biomarkers and enabling preventative treatment targeting early retinal pathology in diabetes.