Optogenetics
In the early 2000s, Pan envisioned implanting a light-sensitive protein, which converts light to electrical signals for
neurons, into the eye to cure blindness. The method is now known as
optogenetics. In the summer of 2004, he used a virus carrying the
channelrhodopsin DNA to infect the
ganglion cells in the eyes of blind mice, and successfully detected electrical activity when the cells were stimulated with light, a "revolutionary" first step in potentially restoring eyesight to the blind. Pan and his collaborator, Alexander Dizhoor, submitted their paper reporting their work to
Nature in November 2004. However, they were directed to the specialized journal
Nature Neuroscience, which rejected the paper. In early 2005, they submitted it to the
Journal of Neuroscience, but were again rejected. In May 2005, Pan presented his work at the Association for Research in Vision and Ophthalmology conference in Florida, which became the clearest public evidence of his invention. Around the same time, other scientists around the world were doing similar research to Pan. In August 2005,
Nature Neuroscience, the same journal that had rejected Pan's paper, published a paper by
Stanford University scientists
Edward Boyden and
Karl Deisseroth describing their work using channelrhodopsin to make neurons detect light. Their research was hailed as a major breakthrough and caught the attention of mainstream media including
The New York Times. When the journal
Neuron finally published Pan's paper in April 2006, it was met with indifference. Boyden and Deisseroth have since been rewarded with major grants and prizes, including
The Brain Prize and the 2015
Breakthrough Prize in Life Sciences with a $3 million prize for each scientist, while Pan only won awards from his own university. In 2016,
Stat News published a report which credits Pan as the inventor of optogenetics and brought attention to his contributions. == RetroSense Therapeutics ==
Publications
• Pan, Z.-H. Differential expression of high- and two types of low-voltage-activated calcium currents in rod and cone bipolar cells of the rat retina. J. Neurophysiol. 83:513–527, 2000. • Pan, Z.-H. and Hu, H.-J. Voltage-dependent Na+ currents in mammalian retinal cone bipolar cells. J. Neurophysiol. 84:2564–2571, 2000. • Pan, Z.-H., Hu, H.-J., Perring, P., and Andrade, R. T-type Ca2+ channels mediate neurotransmitter release in retinal bipolar cells. Neuron 32:89–98, 2001 • Cui, J., Ma, Y.-P., Lipton, S.A., Pan Z.-H. Glycine receptors and glycinergic synaptic input at the axon terminals of mammalian retinal rod bipolar cells. J. Physiol. 553:895–909, 2003. • Bi, A., Cui, J., Ma, Y.-P., Olshevskaya, E., Pu, M., Dizhoor, A.M., and Pan Z.-H. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50:23–33, 2006. • Ivanova, E, Pan, Z.-H. Evaluation of virus mediated long-term expression of channelrhodopsin-2 in the mouse retina. Mol. Vision 15:1680–1689, 2009. • Zhang, Y., Ivanova, E., Bi, A., and Pan, Z.-H. Ectopic expression of multiple microbial rhodopsins restores ON and OFF light responses in the retina after photoreceptor degeneration. J. Neurosci. 29:9186–96, 2009. • Ivanova, E., Hwang, G.-S., Pan, Z.-H., and Troilo, D. Evaluation of AAV-mediated expression of chop2-GFP in the marmoset retina. Invest. Ophthalmol. Vis. Sci. 51:5288–5296, 2010. • Wu, C., Ivanova, E., Cui, J., Lu Q. and Pan. Z.-H. Action potential generation at an AIS-like process in the axonless retinal AII amacrine cell. J. Neurosci. 31:14654–14659, 2011. • Lu, Q., Ivanova, E., Ganjawala, H. T., and Pan, Z.-H. Cre-mediated recombination efficiency and transgene expression patterns of three retinal bipolar cell-expressing Cre transgenic mouse lines. Mol. Vision, 19:1310–1320, 2013 • Wu, C., Ivanova, E., Zhang, Y., Pan, Z.-H. AAV-mediated subcellular targeting of optogenetic tools in retinal ganglion cells. PLOS One, 8(6):e66332, 2013. • Pan, Z.-H., Ganjawala, T.H., Lu, Q., Ivanova, E., and Zhang, Z. ChR2 mutants at L132 and T159 with improved operational light sensitivity for vision restoration. PLOS One, 9(6):e98924, 2014. • Pan, Z.-H., Lu, Q., Bi, A., Dizhoor, A.M., and Abrams, G.W. Optogenetic approaches to restoring vision. Ann. Rev. Vision Sci. 1:185-210, 2015. • Lu, Q., Ganjawala, H.T., Ivanova, E., Cheng, J.G., Troilo, D., and Pan, Z.-H. AAV-mediated transduction and targeting of retinal bipolar cells with improved mGluR6 promoters in rodents and primates. Gene Therapy, 23:680–9, 2016. Source: == References ==