Assessment of murine retinal acuity ex vivo by machine learning of multielectrode array recordings

Project Summary: Darwin Babino, PhD, a trained pharmacologist/electrophysiologist, has
spent the last ten years working on several disciplines in the vision sciences. His proposal
entitled “Assessment of murine retinal acuity ex vivo by machine learning of multielectrode array
recordings” presents his overarching goal to improve vision restoration approaches by
developing methods to test the potential of these techniques thereby accelerating the
development of effective interventions. Dr. Babino and his primary mentor, Dr. Russell Van
Gelder, have assembled a strong team of co-mentors at the University of Washington SOM and
collaborators to guide him through the proposed training and research. His previous training will
be supplemented with goals to help his development as an independent investigator: 1) Study
design and practical learning in performing panretinal (MEA) biological experiments; 2)
Fundamental and advanced techniques of the proposed optogenetic and stem-cell restoration
techniques; 3) Application of advanced machine learning techniques; 4) Develop leadership and
professional skills to establish an independent group. The ability to assess the function of
panretinal circuitry will foster our understanding of the advantages and weaknesses of different
restoration techniques (Aim 1). The work proposed here will improve an existing retinal acuity
assessment tool which combines machine learning techniques on novel, high-density
multielectrode array recordings of ganglion cell responses in several mouse models. The utility
of this system will be demonstrated in assessing visual potential of the mouse retina in three
different approaches to vision restoration that are challenging for in vivo assessment (Aim 2). In
collaboration with Dr. Deepak A. Lamba at UCSF, we will apply our system to animals which
have undergone stem-cell replacement of retinal cells including photoreceptor cells. An
optogenetics approach will also be evaluated in collaboration with Dr. John Flannery at UC
Berkeley whose group has developed vectors for expressing rhodopsin and cone opsins in
ganglion and bipolar cells. Finally, differences between native and restored vison with small
molecule photoswitches, light-activated inhibitors of voltage-gated potassium channels, which
confer light-dependent firing on treated cells, will be assessed. The resulting advanced
electrophysiology application will help elucidate fundamental questions about the functional
retina, mechanisms that lead to retinal degeneration and the potential of several therapeutics for
the treatment of retinal diseases. Furthermore, this career development award will facilitate Dr.
Babino’s development into an independent investigator by priming an R01 grant application.

Grant Number: 5R00EY031333-04
NIH Institute/Center: NIH
Principal Investigator: Darwin Babino