Studying the Eye’s Cellular Mechanisms
The Krizaj lab is interested in "what makes cells alive." The main research model, the retinal photoreceptor, is a complex and highly specialized sensory neuron whose function is to transform light into electrical impulses. This transformation is directly related to our ability to perceive light.
Dr. Krizaj's lab was the first to characterize the identity, function and developmental profile of calcium ATPase (PMCA) transporters that mediate the light response and protect photoreceptors from calcium overload that represents the "death signal" in degenerating photoreceptors. Using calcium imaging techniques, ERG and patch clamp recordings in knockout animals they showed that loss of specific PMCA isoforms compromises transmission of the visual signal from photoreceptors to the brain.
A second project is focused on the mechanisms through which rod and cone photoreceptors store calcium in intracellular organelles, such as the endoplasmic reticulum and the mitochondria. Dr. Krizaj's lab demonstrated for the first time that dynamic regulation of SERCA transporters and ryanodine receptors that release calcium from internal stores is essential for transmission of the visual signal from photoreceptors. Importantly, rod and cone photoreceptors subserving night and daytime vision were found to express different sets of these calcium transporters and channels. Current work shows that novel calcium-binding proteins are dramatically overexpressed during blinding diseases, representing an ideal target for therapeutic interventions.
Taken together, these studies, funded by the National Eye Institute, Research to Prevent Blindness and other private foundations show that the living photoreceptor cell is an intricate polarized cell which coordinates its metabolism, light adaptation, gene expression, synaptic transmission as well as cell death through calcium fluxes mediated by calcium signaling proteins and organelles localized to specialized subdomains. The goal of future research is to understand how these processes are regulated dynamically during the light response and how they can be modulated to alleviate the degeneration process.