Posts tagged ‘retinal degeneration’

In May 2017, the Leung lab visited several collaborating groups in Asia and shared with them our research vision on using zebrafish to find new drugs for retinal degeneration. In this blog post, we will share some pictures of our visit to the Department of Ophthalmology at the Osaka University School of Medicine. We met our long-term collaborator Dr. Motokazu Tsujikawa. He is a co-mentor of Logan Ganzen, a graduate student in our laboratory. Logan is a recipient of the predoctoral award from the Indiana Clinical and Translational Sciences Institute. During our Osaka trip, he presented a talk entitled “Visual Motor Response of a Transgenic Retinitis Pigmentosa Zebrafish Model” to Dr. Tsujikawa.


Logan in front of a new Center for Medical Innovation and Translational Research.

Fai and Dr. Motokazu in his zebrafish facility in the Center of Medical Innovation and Translational Research.

The Center is beautifully designed with lots of open space.

Logan presented his latest findings to Dr. Motokazu, who served as a co-mentor in Logan’s CTSI predoctoral fellowship.

We also visited the daily operation of the ophthalmology clinic and Osaka University Hospital, and participated in the grand rounds of the local ophthalmologists. We experienced firsthand the passion of translational research from our Japanese colleagues.

Entrance hall of the medical building

A panoramic view at the top floor of the hospital.

We joined the grand rounds of the local ophthalmologists. Dr. Kohji Nishida welcomed the group and gave an opening speech.  Even though we did not speak Japanese, we witnessed their passion to improve clinical service through research.

Needless to say, we were also well-fed by Dr. Tsujikawa with the finest Japanese food, and took some time to visit Kyoto, a magnificent ancient city.

Dr. Motokazu fed us with delicious Japanese food!

A torii path at the Fushimi Inari Taisha in Kyoto.

Kinkaku-ji in Kyoto

I have just come across an interesting approach to help patients with poor vision–using a smartphone app designed for augmenting vision with google cardboard.

I first came across this approach through this youtube video. It shows how the approach helped a lady who suffered from Stargardt’s disease and could not see well for eight years.

After using the app and google cardboard, she seemed to see much better and was so excited by the experience. I find this interesting because many of my friends and relatives suffered from poor vision. They can potentially see better through this simple and cheap approach. I am going to set this up for my parents soon and see if that helps them see better!


Gene regulatory network

  1. Barsi JC, Tu Q, Davidson E. General approach for in vivo recovery of cell type specific effector gene sets. Genome Res. 2014 Mar 6. [Epub ahead of print] PubMed PMID: 24604781.


  1. Project to Improve Poor Children’s Intellect Led to Better Health, Data Show
  2. Begley CG, Ellis LM. Drug development: Raise standards for preclinical cancer research. Nature. 2012 Mar 28;483(7391):531-3. doi: 10.1038/483531a. PubMed PMID: 22460880.


  1. Portugues R, Feierstein CE, Engert F, Orger MB. Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior. Neuron. 2014 Mar 19;81(6):1328-43. doi: 10.1016/j.neuron.2014.01.019. PubMed PMID: 24656252.
  2. Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. Cerebral organoids model human brain development and microcephaly. Nature. 2013 Sep 19;501(7467):373-9. doi: 10.1038/nature12517. Epub 2013 Aug 28. PubMed PMID: 23995685; PubMed Central
    PMCID: PMC3817409.

    • Brüstle O. Developmental neuroscience: Miniature human brains. Nature. 2013
      Sep 19;501(7467):319-20. doi: 10.1038/nature12552. Epub 2013 Aug 28. PubMed PMID: 23995687.

Genome editing

  1. Auer TO, Del Bene F. CRISPR/Cas9 and TALEN-mediated knock-in approaches in zebrafish. Methods. 2014 Apr 1. pii: S1046-2023(14)00129-7. doi: 10.1016/j.ymeth.2014.03.027. [Epub ahead of print] PubMed PMID: 24704174.
  2. Zhou Y, Zhu S, Cai C, Yuan P, Li C, Huang Y, Wei W. High-throughput screening
    of a CRISPR/Cas9 library for functional genomics in human cells. Nature. 2014 Apr
    9. doi: 10.1038/nature13166. [Epub ahead of print] PubMed PMID: 24717434.
  3. Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp
    PA, Jacks T, Anderson DG. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol. 2014 Mar 30. doi: 10.1038/nbt.2884. [Epub ahead of print] PubMed PMID: 24681508.

Stem cells

  1. Becker S, Jayaram H, Limb GA. Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration. Cells. 2012 Oct 18;1(4):851-73. doi: 10.3390/cells1040851. PubMed PMID: 24710533.
  2. Assawachananont J et al., Transplantation of Embryonic and Induced Pluripotent Stem Cell-Derived 3D Retinal Sheets into Retinal Degenerative Mice. Stem Cell Reports. 2014; 2: 662-674.

Retinal degeneration

  1. Wasfy MM, Matsui JI, Miller J, Dowling JE, Perkins BD. myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses. Exp Eye Res. 2014 Apr 1. pii: S0014-4835(14)00083-9. doi: 10.1016/j.exer.2014.03.007. [Epub ahead of print] PubMed PMID: 24698764.

Retinal development

  1. Weber IP, Ramos AP, Strzyz PJ, Leung LC, Young S, Norden C. Mitotic Position and Morphology of Committed Precursor Cells in the Zebrafish Retina Adapt to Architectural Changes upon Tissue Maturation. Cell Rep. 2014 Apr 2. pii: S2211-1247(14)00192-2. doi: 10.1016/j.celrep.2014.03.014. [Epub ahead of print] PubMed PMID: 24703843.
  2. Almeida AD, Boije H, Chow RW, He J, Tham J, Suzuki SC, Harris WA. Spectrum of Fates: a new approach to the study of the developing zebrafish retina. Development. 2014 Apr 9. [Epub ahead of print] PubMed PMID: 24718991.
  3. Yoshimatsu T, Williams PR, D’Orazi FD, Suzuki SC, Fadool JM, Allison WT, Raymond PA, Wong RO. Transmission from the dominant input shapes the stereotypic ratio of photoreceptor inputs onto horizontal cells. Nat Commun. 2014 May 15;5:3699. doi: 10.1038/ncomms4699. PubMed PMID: 24832361.


  1. Bianchi E, Doe B, Goulding D, Wright GJ. Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature. 2014 Apr 24;508(7497):483-7. doi: 10.1038/nature13203. Epub 2014 Apr 16. PubMed PMID: 24739963; PubMed Central PMCID: PMC3998876.

Genetics/Synthetic biology

  1. Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Corrêa IR Jr, Romesberg FE. A semi-synthetic organism with an expanded genetic alphabet. Nature. 2014 May 15;509(7500):385-8. doi: 10.1038/nature13314. Epub 2014 May 7. PubMed PMID: 24805238.
    • Commentary: Thyer R, Ellefson J. Synthetic biology: New letters for life’s alphabet. Nature. 2014 May 15;509(7500):291-2. doi: 10.1038/nature13335. Epub 2014 May 7. PubMed PMID: 24805244.

Genome editing

  1. Kim JM, Kim D, Kim S, Kim JS. Genotyping with CRISPR-Cas-derived RNA-guided endonucleases. Nat Commun. 2014 Jan 20;5:3157. doi: 10.1038/ncomms4157. PubMed PMID: 24445736.
  2. Bae S, Park J, Kim JS. Cas-OFFinder: A fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics. 2014 Jan 24. [Epub ahead of print] PubMed PMID: 24463181.
  3. Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014 Jan 26. doi: 10.1038/nbt.2808. [Epub ahead of print] PubMed PMID: 24463574.
  4. Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, Ma E, Anders C, Hauer M, Zhou K, Lin S, Kaplan M, Iavarone AT, Charpentier E, Nogales E, Doudna JA. Structures of Cas9 Endonucleases Reveal RNA-Mediated Conformational Activation.
    Science. 2014 Feb 6. [Epub ahead of print] PubMed PMID: 24505130.
  5. Sternberg SH, Redding S, Jinek M, Greene EC, Doudna JA. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature. 2014 Jan 29. doi: 10.1038/nature13011. [Epub ahead of print] PubMed PMID: 24476820.
  6. Nishimasu H, Ran FA, Hsu PD, Konermann S, Shehata SI, Dohmae N, Ishitani R, Zhang F, Nureki O. Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA. Cell. 2014 Feb 12. pii: S0092-8674(14)00156-1. doi: 10.1016/j.cell.2014.02.001. [Epub ahead of print] PubMed PMID: 24529477.
  7. Niu Y, Shen B, Cui Y, Chen Y, Wang J, Wang L, Kang Y, Zhao X, Si W, Li W, Xiang AP, Zhou J, Guo X, Bi Y, Si C, Hu B, Dong G, Wang H, Zhou Z, Li T, Tan T, Pu X, Wang F, Ji S, Zhou Q, Huang X, Ji W, Sha J. Generation of Gene-Modified Cynomolgus Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos. Cell. 2014 Jan 30;. [Epub ahead of print]
  8. Hai T, Teng F, Guo R, Li W, Zhou Q. One-step generation of knockout pigs by zygote injection of CRISPR/Cas system. Cell Res. 2014 Jan 31;. [Epub ahead of print]
  9. Heigwer F, Kerr G, Boutros M. E-CRISP: fast CRISPR target site identification. Nat Methods. 2014 Jan 30;11(2):122-3.
  10. Nakagawa Y, Yamamoto T, Suzuki K, Araki K, Takeda N, Ohmuraya M, Sakuma T. Screening Methods to Identify TALEN-Mediated Knockout Mice. Exp Anim. 2014;63(1):79-84. PubMed PMID: 24521866.


  1. Simões-Costa M, Tan-Cabugao J, Antoshechkin I, Sauka-Spengler T, Bronner ME. Transcriptome analysis reveals novel players in the cranial neural crest gene regulatory network. Genome Res. 2014 Jan 3. [Epub ahead of print] PubMed PMID: 24389048.
  2. Umulis DM, Othmer HG. Mechanisms of scaling in pattern formation. Development. 2013 Dec;140(24):4830-43. doi: 10.1242/dev.100511. Review. PubMed PMID: 24301464; PubMed Central PMCID: PMC3848184.
  3. Pauli A, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman S, Mitchell A, Ma J, Dubrulle J, Reyon D, Tsai SQ, Joung JK, Saghatelian A, Schier AF. Toddler: An Embryonic Signal That Promotes Cell Movement via Apelin Receptors. Science. 2014 Jan 9. [Epub ahead of print] PubMed PMID: 24407481.
  4. Dias AS, de Almeida I, Belmonte JM, Glazier JA, Stern CD. Somites without a clock. Science. 2014 Feb 14;343(6172):791-5. doi: 10.1126/science.1247575. Epub 2014 Jan 9. PubMed PMID: 24407478.
    • Kondo S. Developmental biology. Self-organizing somites. Science. 2014 Feb 14;343(6172):736-7. doi: 10.1126/science.1250245. PubMed PMID: 24531958.


  1. Zhang Y, Vastenhouw NL, Feng J, Fu K, Wang C, Ge Y, Pauli A, van Hummelen P, Schier AF, Liu XS. Canonical nucleosome organization at promoters forms during genome activation. Genome Res. 2014 Jan 8. [Epub ahead of print] PubMed PMID:

Retinal degeneration/regeneration

  1. Sherpa T, Lankford T, McGinn TE, Hunter SS, Frey RA, Sun C, Ryan M, Robison BD, Stenkamp DL. Retinal regeneration is facilitated by the presence of surviving neurons. Dev Neurobiol. 2014 Feb 1. doi: 10.1002/dneu.22167. [Epub ahead of print] PubMed PMID: 24488694.
  2. Cruz NM, Yuan Y, Leehy BD, Baid R, Kompella U, Deangelis MM, Escher P, Haider NB. Modifier genes as therapeutics: the nuclear hormone receptor rev erb alpha (nr1d1) rescues nr2e3 associated retinal disease. PLoS One. 2014;9(1):e87942.


  1. Mueller KP, Neuhauss SC. Sunscreen for Fish: Co-Option of UV Light Protection for Camouflage. PLoS One. 2014 Jan 29;9(1):e87372. doi: 10.1371/journal.pone.0087372. eCollection 2014. PubMed PMID: 24489905.

Stem cells

  1. Stress-Induced Stem Cell Method Questioned


In January, I visited the Center for Human Molecular Biology & Genetics at the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China [Chinese website of the Institute]. It is a large provincial hospital in Sichuan Province with a population of 80.8 million. The hospital served approximately 3.6 million outpatient and emergency cases, and carried out almost 75,000 surgeries in 2011. With this number of patients, the Center for Human Molecular Biology & Genetics collected extensive human samples and has been a leader in genetics study in China.

Prof. Zhengli Yang, the vice president of the hospital and the director of Center for Human Molecular Biology & Genetics, invited both me and a renowned eye geneticist Prof. Shomi Bhattacharya to discuss our current research on eye disease therapy. I discussed how my lab is setting up the foundation to use zebrafish to screen eye drugs at Purdue. Prof. Bhattacharya discussed his work on gene therapy and stem cell therapy. It was a great experience to interact with a world leader in genetics whom discovered many of the key genes in retinal degeneration, and a top notch research institution in China.

Yuk Fai Leung lectured at the Center for Human Molecular Biology & Genetics, the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China


Prof. Shomi Bhattacharya lectured at the Center for Human Molecular Biology & Genetics, the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China. Prof. Zhenglin Yang (right) hosted the symposium.


Audience from the Center for Human Molecular Biology & Genetics, the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China.

I visited Ho Yu College in Hong Kong last month. A good mentor Dr. William Mak has been running a great biotechnology education program for the primary and secondary school students, as well as the public there. See an old post about their outreach program in which they fit a whole research lab into custom-built bus! I shared the research program of our laboratory at Purdue University on using zebrafish to screen drugs for vision benefit.


I outlined our approach on using simple visual behaviour assays to identify positive effects of drugs. I specifically emphasized on the potential to analyze many of traditional Chinese medicines; the treasure that we have been consuming for generations. Some of these possibilities are outlined in our recent review paper:

Zhang LY, Chong L, Cho J, Liao PC, Shen F, Leung YF. Drug Screening to Treat Early-Onset Eye Diseases: Can Zebrafish Expedite the Discovery? Asia-Pac J Ophthalmol 2012; 1:374-383. [Full text][pdf]


The interaction with the students was fantastic. They were very imaginative and eager to ask questions all the time! Their enthusiasm was infectious and is the driving force of scientific progress. That also reminded me of the problem of our education in stifling creativity when students are “educated”, which I wrote in a separate post recently.

This is truly an enjoyable experience and I look forward to visiting them again soon!


  1. Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A.  Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science. 2012 Jun 8;336(6086):1317-21. PubMed PMID: 22679098.


  1. Polverino G, Abaid N, Kopman V, Macrì S, Porfiri M. Zebrafish response to robotic fish: preference experiments on isolated individuals and small shoals. Bioinspir Biomim. 2012 Jun 8;7(3):036019. [Epub ahead of print] PubMed PMID: 22677608.

Systems Biology

  1. Ku CJ, Wang Y, Weiner OD, Altschuler SJ, Wu LF. Network Crosstalk Dynamically Changes during Neutrophil Polarization. Cell. 2012 May 25;149(5):1073-83. PubMed PMID: 22632971.

Human Microbiome

  1. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. doi:10.1038/nature11234. PubMed PMID: 22699609.
  2. Human Microbiome Project Consortium. A framework for human microbiome research. Nature. 2012 Jun 13;486(7402):215-21. doi: 10.1038/nature11209. PubMed PMID: 22699610.
    • Commentary: Relman DA. Microbiology: Learning about who we are. Nature. 2012 Jun 13;486(7402):194-5. doi: 10.1038/486194a. PubMed PMID: 22699602.

Retinal degeneration

  1. Taylor S, Chen J, Luo J, Hitchcock P. Light-induced photoreceptor degeneration in the retina of the zebrafish. Methods Mol Biol. 2012;884:247-54. PubMed PMID: 22688711.


  1. Cyranoski D. Neuroscience: The mind reader. Nature. 2012 Jun 13;486(7402):178-80. doi: 10.1038/486178a. PubMed PMID: 22699592.
  2. Van Horn JD, Irimia A, Torgerson CM, Chambers MC, Kikinis R, Toga AW. Mapping connectivity damage in the case of phineas gage. PLoS One. 2012;7(5):e37454. Epub 2012 May 16. PubMed PMID: 22616011; PubMed Central PMCID: PMC3353935.

Retinal development

  1. Stacher Hörndli C, Chien CB. Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk. Development. 2012 Jun 13. [Epub ahead of print] PubMed PMID: 22696293.