Amy Bucklaew¹, David Fernandez¹, Sara Patterson^1,2; ¹Center for Visual Science, University of Rochester, ²Flaum Eye Institute and Department of Neuroscience, University of Rochester Medical Center

Stroke induced vision loss is a prevalent source of visual impairment, resulting in nearly 100,000 new cases of hemianopia in the US and Europe each year (Sahraie et al 2007). While there is potential for training-induced vision restoration (Saionz et al 2020), the limited efficacy means that cortically induced blindness (CB) remains a permanent condition for most patients (Zhang et al 2006b). A key factor likely to affect visual recovery is the extent of trans-synaptic retrograde degeneration (TRD) in upstream areas such as the LGN and the retinal ganglion cells (RGCs). Prior investigations of the TRD in RGCs have been limited by the resolution achievable through the eye’s optics. These challenges have been overcome by combining calcium imaging with adaptive optics scanning light ophthalmoscopy (AOSLO) to allow for visualization of foveal RGC function in the living primate eye. To investigate TRD at the level of individual RGCs, we created a marmoset model of stroke by unilaterally lesioning area V1 with ibotenic acid. The marmoset is advantageous as a model due to its smooth cortex, which facilitates cortical targeting, and its comparable visual circuitry to humans. We constructed an extension of a macaque AOSLO system to target the marmoset eye by custom designing a marmoset-specific stereotax, optically scaling down the system’s pupil size, and optimizing anesthesia/paralysis techniques to facilitate imaging in the marmoset. We can now image the marmoset cone mosaic in vivo for the first time. Next, we performed intravitreal injections of a calcium indicator, GCaMP8s, into each eye to label RGCs and enable functional imaging. Unlike other retinal physiology methods, our approach is both non-invasive and allows for the opportunity to re-image the same population of foveal RGCs for months or years during the progression of TRD.

Acknowledgements: Research was supported by the National Eye Institute of the National Institutes of Health under R00-EY035323, P30 EY001319. Research was also supported by an Unrestricted Grant to the University of Rochester Department of Ophthalmology from Research to Prevent Blindness, New York, New York.