Ryan Bloch L&S Biological Sciences
Investigating PiT2-Mediated Phosphate Homeostasis in Cataractogenesis
Cataracts, the leading cause of blindness, result from clouding of the eye lens. While cataract etiology is well known, complete molecular mechanisms remain unclear. One key mechanism involves age-related loss of gap junction function. Studies in connexin knockout models have shown this loss elevates calcium levels in lens cells. This causes overactivation of calcium-dependent proteases, resulting in aberrant cleavage of structural proteins that then aggregate and cloud the lens. Less studied are the calcium salt deposits observed in these models, resembling those in soft tissue calcification driven by phosphate dysregulation. Slc20a2 encodes the sodium-phosphate cotransporter PiT2, mutations of which cause brain calcification. The Gong Lab recently characterized cataracts in Slc20a2KO mice. We hypothesize PiT2 is necessary for transport of phosphate into lens cells and that altered phosphate homeostasis causes calcium salt precipitation and cataract formation. My project uses in vitro methods to localize PiT2 in lens cells and investigate how changes in extracellular phosphate affect calcium homeostasis, offering insights into a novel, understudied pathway in cataractogenesis.
Message To Sponsor
Thank you so much for sponsoring my SURF project! At such a tumultuous time for science funding, I am especially grateful that undergraduate students can still pursue research thanks to the generosity of private donors. I am excited to explore how phosphate transport by PiT2 influences calcium dynamics in the lens—a question that could uncover a novel mechanism behind cataract formation. I will use this opportunity to build technical skills and deepen my understanding of scientific research.