;/ Sonata Bis 9 /NSC

Development of a method to restore visual function using a modified rabies virus

Eye, and particularly the retina, is a “window into the brain”. It reveals sufficient information about
patient condition, and for humans, it is the main organ responsible for world perception. The retina
is a very fragile and complex structure, located on the back of the eyes and is exposed to many
environmental hazards leading to its defects or even retinal degeneration (RD). In modern society,
an increasing number of people suffering from visual impairment are being observed. The
predominant causes of visual impairments are irreversible changes in the retinal structure and
mutations leading to photoreceptor (our light detectors) death in the retina. Two main diseases
related to photoreceptor death are retinitis pigmentosa and age-related macular degeneration
which are causing blindness/vision loss in ~200 million people globally. Without question, these
conditions significantly reduce the quality of life and, therefore, drive a strong need for developing
new, easy to use and effective techniques for not only slowing down the disease progression but
also restoring vision. There have been a large number of attempts aiming to prevent complete loss
of photoreceptors or restoring vision by either opsin delivery or retinal transplantation. The viral
gene therapy based on delivering light-sensitive ion channels to surviving retinal cells seems the
most direct way of curing blindness. However, a number of issues remain to be solved in order to
create an effective therapy. The general aim of this project is to develop a new approach to
deliver light-sensitive ion channels in order to restore selective neuronal responses to low
light stimuli in the visual system of a blind animal. To do so we will use a modified Rabies virus
(RV) tracing technique that allows not only for efficient gene expression but also cell-type-specific
network tracing to precisely deliver proteins of interest to the desired retinal circuit. This approach
is crucial to obtain adequate light sensitivity and restore selective visually evoked responses in the
brain. It will also create a specific functional network that will mimic the natural processing of the
The Rabies virus will be used for opsin delivery into the degenerated retina to restore visual
responses in the blind animals. Visual responses will be tested in the primary visual cortex for not
only sensitivity to flash of light but also for selectivity to certain stimulus parameters like contrast,
spatial frequency, orientation/direction, and size. It is crucial to investigate whether viral/gene
therapy can restore selective neuronal responses in the visual system. We take full advantage of
the hierarchical connectivity of the retinal network to target different functional circuits and
information processing channels by infecting different retinal layers through monosynaptic viral
This unique method will reveal the extent to which the visual system will respond to
complex stimuli like moving spots, drifting gratings, pattern motion, and natural stimuli
after viral treatment.