The recent special issue of the American Journal of Medical Genetics; Seminar in Medical Genetics (Volume 184, Issue 3) includes contributions from four AVN labs: Waskiewicz, Lehmann, Walter, and MacDonald. Check out the issue to learn more about ocular coloboma, retinal dystrophies, and more: AJMG Ocular Genetics
Nate defended his MSc thesis (Form and Function of Photoreceptors in kcnv2 Mutant Zebrafish: Implications for the Human Disease KCNV2 Retinopathy) last Thursday. After giving a great talk, he passed without revisions! Congrats to Nate on being the first student to graduate from the Hocking lab, and all the best to him as he starts his first year of medical school at the University of Alberta.
Darpan Malhotra defended his PhD in June 2019, with Bob Molday doubling as his external examiner and our AVN Research Day keynote speaker (see photo of Bob, Darpan, and Joe). The Casey lab is still publishing papers based on Darpan’s impressive body of work about the SLC4A11 corneal transporter. To learn more, check out these publications:
Malhotra, D. and Casey, J.R. (2020) Molecular Mechanisms of Fuchs and Congenital Hereditary Endothelial Corneal Dystrophies Reviews in Physiology, Biochemistry and Pharmacology, In Press.
Malhotra, D., Jung,M., Fecher-Trost, C., Lovatt, M., Peh, G.S.L, Noskov, S., Mehta, J.S., Zimmermann, R., and Casey, J.R. (2020) Defective Cell Adhesion Function of Solute Transporter, SLC4A11, in Endothelial Corneal Dystrophies, Human Molecular Genetics, 29, 97-116.
Malhotra, D., Chiu, A.M., Loganathan, S.K., Lukowski, C.M. and Casey, J.R. (2019) Identification of SLC4A11 Translational Product in Human Cornea, Scientific Reports, 9, 9681.
Lab research is always full of ups and downs, but it’s been more topsy-turvy than ever in 2020. We thought we’d take this opportunity to highlight accomplishments of our AVN labs over the past year. Stay tuned over the coming weeks….
A recent paper from the Hocking Lab describes a simple method for obtaining electroretinogram measurements from zebrafish. Excitingly, it works for larval, juvenile and adult fish. Well done Nate Nadolski on your success following painstaking work to develop the new procedure.
Nadolski NJ, Wong CXL, Hocking JC. Electroretinogram analysis of zebrafish retinal function across development. Doc Ophthalmol. 2020. doi:10.1007/s10633-020-09783-y
A paper in press at Human Molecular Genetics (Lahola-Chomiak et al., https://www.ncbi.nlm.nih.gov/pubmed/30561643) reports the results of a collaboration led by Dr. Michael Walter, and involving the Lehmann and Allison labs. This work discovered the first causative gene for pigmentary glaucoma, a common subtype of glaucoma, which represents the leading cause of irreversible blindness worldwide.
Dr. Walter’s team first identified a mutation in the premelanosome (PMEL) gene in DNA samples from two Mennonite cousins before identifying additional PMEL mutations in a cohort of patients with pigmentary glaucoma. Molecular analyses demonstrate that these mutations alter the function of the PMEL protein, and CRISPR-CAS9 mutagenesis of pmel in zebrafish resulted in both pigment defects and glaucoma-like phenotypes. In parallel, colleagues at Harvard and the University of Flinders (Drs. Wiggs and Craig), identified PMEL mutations in additional pigmentary glaucoma cases, strongly supporting the role of PMEL mutations in PG. Overall, these results improve understanding of the etiology of a major form of blindness, with opportunities for novel approaches for diagnosing and eventually treating this common form of glaucoma.
Figure 1. Typical signs of pigmentary glaucoma (pigment granules on the corneal endothelium, heavy pigmentation of the trabecular meshwork, and iris trans-ilumination defects.
Figure 2. pmel CRISPR-generated zebrafish mutant demonstrating globe enlargement (a feature of congenital glaucoma in infants).
Nicole is working on her PhD thesis under two AVN members, Dr. Ian McDonald and Dr. Ted Allison. Congratulations to Nicole for receiving a CIHR Canada Graduate Scholarship to support her during her studies.
A recently published paper in PLoS Genetics (Hocking et al., March 2018) is the culmination of a long-standing collaborative project by two AVN labs (PIs: Ordan Lehmann and Andrew Waskiewicz). The group identified eight patients with tissue gaps in the superior portion of the iris, retina, and/or lens – a novel congenital disease the researchers termed Superior Coloboma. By using zebrafish to revisit ocular development, the authors discovered the superior ocular sulcus, a transient groove bisecting the dorsal retina and the potential origin of superior coloboma. Moreover, they showed how patterning cues control formation and closure of the sulcus and its developmental function in directing growing ocular blood vessels.
Lance (MacDonald Lab) recently received a Retina Foundation of Canada Clinical Research Grant that will support his research into novel causes of retinal and macular dystrophies.