Department of Physics, University of California, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, United States
Yuhan Yang
Department of Physics, University of California, Berkeley, United States
Kevin J Cao
Department of Molecular and Cell Biology, University of California, Berkeley, United States; Helen Wills Neuroscience Institute, University of California, Berkeley, United States
Wei Chen
Department of Physics, University of California, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, United States
Santosh Paidi
School of Optometry, University of California, Berkeley, United States
Chun-hong Xia
School of Optometry, University of California, Berkeley, United States; Vision Science Program, University of California, Berkeley, United States
Department of Molecular and Cell Biology, University of California, Berkeley, United States; Helen Wills Neuroscience Institute, University of California, Berkeley, United States; Vision Science Program, University of California, Berkeley, United States
Department of Physics, University of California, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, United States; Helen Wills Neuroscience Institute, University of California, Berkeley, United States; Vision Science Program, University of California, Berkeley, United States; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States
The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving putative synaptic structures and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions with sub-capillary details in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high-resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo.
