Researcher

Title

• Directeur, département d'ophtalmologie, Université de Montréal (2024)
• Directeur et titulaire de la Chaire Suzanne Véronneau-Troutman, M.D. FRCSC, FACS
• Professeur titulaire de clinique, département d'ophtalmologie, Université de Montréal
• Chercheur, Centre de recherche Azrieli du CHU Sainte-Justine (2024)

• Université McGill M.D., C.M. 1979
• Université McGill M.Sc. (biologie) 1972

With funding from the Canadian Foundation for Innovation, the Canadian Institutes for Health Research, Alberta Innovates-Health Solutions, Fighting Blindness Canada, and the Choroideremia Research Foundation, Canada Inc., I led the first clinical trial of ocular gene therapy in Canada, a trial in choroideremia (CHM) patients. I am currently researching an antisense oligonucleotide treatment for a specific intronic variant in the CHM gene.

• Inherited retinal disorders
• Visual electrophysiology
• Ocular genetics
• Clinical trials
• Ocular gene therapy (RNA and AAV)

Career Summary

With board-certification in clinical genetics and ophthalmology, I have researched the complexities of inherited retinal disorders (IRDs) throughout my career.  My professional career began in Ottawa as an Ontario Ministry of Health career scientist. In 1992, I moved to Alberta where I served 4 terms as Chair of the Department of Ophthalmology and Visual Sciences, University of Alberta. I was on staff for two years (2007-8) as Branch Chief, Ophthalmic Genetics and Visual Function of the National Eye Institute, NIH before returning to Edmonton to set up a research program of ocular gene therapy. In August 2024, I moved to Montreal, as Director of the Department of Ophthalmology. My intention is to build a research team in Montreal to test therapies for inherited ocular traits and help build translational research capacity.

My laboratory made several contributions including: 1) identifying choroideremia’s (CHM)  natural promoter, 2) demonstrating duplications in the CHM gene, 3) identifying inversions in CHM, 4) identifying cryptic splice sites that can be treated with anti-sense oligonucleotides, and 5) researching a synonymous variant that creates hnRNPA1/2 binding sites that suppress normal splicing.

Laboratory

MacDonald laboratory for translational eye research

Awards and Distinctions

• 2022 - Silver Fellow, Association for Research on Vison and Ophthalmology
• 2021 - Francescetti Medal, International Society for Genetic Eye Disease and Retinoblastoma.
• 2020 - Canadian College of Medical Geneticists for Lifetime Achievement
• 2018 - Foundation Fighting Blindness, Canada. Founder’s Award

Presentations

1. MacDonald, I M. 9 mai 2025. Precision Medicine in Ophthalmology. Genetic therapies. JD Allen Lecture. Journée de recherche en ophtalmologie, Département d’ophtalmologie, U Ottawa
2. MacDonald IM, Xu M, Han T, Sauvé Y, Rudnisky C. 4 mai 2025. SLE patients tolerate a high cumulative dose of HCQ without developing retinopathy. ISCEV@ARVO. Salt Lake City, Utah
3. MacDonald, I.M. 10 fevr. 2025. Opportunités et défis de la thérapie génique oculaire. Groupe de recherche en science de la vision. Conférences Nikon. École d’optométrie, U Montréal.

Publications

1. Doucette LP, Noel NCL, Zhai Y, Xu M, Caluseriu O, Hoang SC, Radziwon AJ, MacDonald IM. Whole exome sequencing reveals putatively novel associations in retinopathies and drusen formation. Eur J Hum Genet. 2021 Mar 29. doi: 10.1038/s41431-021-00872-3. Epub ahead of print. PMID: 33776059.
2. MacDonald IM. Lessons learned from research on choroideremia. Ophthalmic Genet. 2022 Jan 26:1-8. doi: 10.1080/13816810.2022.2025608. PMID: 35080186
3. Noel NCL, Allison WT, MacDonald IM, Hocking JC. Zebrafish and inherited photoreceptor disease: Models and insights. Prog Retin Eye Res. 2022 Jul 7:101096. doi:10.1016/j.preteyeres.2022.101096. PMID: 35811244.
4. Benson MD, Papp KM, Casey GA, Radziwon A, St. Laurent CD, Doucette LP, MacDonald IM 2021. PEX6 mutations in peroxisomal biogenesis disorders: An Usher syndrome mimic. Ophthalmology Science. 2022; 1:1-12.
5. Chrystal PW, et al., MacDonald IM, Arno G, Leroux MR. The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision. Nat Commun. 2022 Nov 3;13(1):6595. doi: 10.1038/s41467-022-33820-w. PMID: 36329026.
6. Birch, DG, Cheetham JK, Daiger SP, Hoyng C, Kay C, MacDonald IM, Pennesi ME, Sullivan LS. Overcoming the challenges to clinical development of X-linked retinitis pigmentosa therapies: Proceeding of an expert panel. Transl Vis Sci Technol 2023;12(6):5, https://doi.org/10.1167/tvst.12.6.5
7. Zhai Y, Xu M, Radziwon A, Dimopoulos IS, Crichton P, Mah R, MacLaren RE, Somani R, Tennant MT, MacDonald IM. AAV2-mediated gene therapy for Choroideremia: 5-Year results and alternate anti-sense oligonucleotide therapy. Am J Ophthalmol. 2023; 248:145-156. doi: 10.1016/j.ajo.2022.12.022. PMID: 36581191.
8. Havrylov S, Chrystal P, van Baarle S, French CR, MacDonald IM, Avasarala J, Rogers RC, Berry FB, Kume T, Waskiewicz AJ, Lehmann OJ. Pleiotropy in FOXC1-attributable phenotypes involves altered ciliation and cilia-dependent signaling. Sci Rep. 2024; 14:20278. PMID: 39217245
9. Misaghi E, Kannu P, MacDonald IM, Benson MD. Genetic variants in PIKFYVE: A review of ocular phenotypes. Exp Eye Res. 2025; 251:110211. PMID: 39694407.
10. Toay S, Sheri N, MacDonald I, Sergeev YV. Human recombinant tyrosinase destabilization caused by the double mutation R217Q/R402Q. Protein Sci. 2025 Feb;34(2):e70029. doi: 10.1002/pro.70029. PMID: 39840795.