The most common cause of dominant retinitis pigmentosa is mutations in the rhodopsin gene, which lead to the death of rod photoreceptors. A subset of patients develop a form known as sector retinitis pigmentosa, in which the lower portion of the retina is more severely affected, likely because light exposure exacerbates the disease. This phenotype suggests that the condition may, at least in part, be preventable, since degeneration has already been delayed or avoided in a significant fraction of the retina.
In this seminar, Prof. Orson L. Moritz will present research using transgenic Xenopus laevis tadpoles to model disease caused by several sector RP-associated mutations. These studies reveal that light can promote retinal degeneration through multiple mechanisms, including biosynthetic defects, phototoxicity and abnormal rhodopsin aggregation. He will also discuss how animal models with different genotypes respond very differently to therapeutic interventions, underscoring the importance of understanding which disease mechanisms are present in particular patients.
The presentation will focus especially on a mechanism termed chromophore-exacerbated degeneration, including its genetic and environmental interactions, its relative prevalence in sector RP and its potential therapeutic implications.
About the speaker
Prof. Orson L. Moritz is a Full Professor in the Department of Ophthalmology & Visual Sciences at the University of British Columbia, Canada. He completed his undergraduate degree in Biochemistry and Molecular Biology at the University of British Columbia, followed by a PhD in the laboratory of Dr. Robert S. Molday, where he investigated the biochemical properties of Prph2 and Rom1.
He later joined the laboratory of Dr. David S. Papermaster at the University of Connecticut as a postdoctoral fellow. There, together with his research partner Beatrice M. Tam, he developed transgenic Xenopus laevis as a model system for investigating photoreceptor cell biology, with a particular focus on rhodopsin trafficking and targeting.
After returning to the University of British Columbia as an assistant professor, Prof. Moritz continued to advance the transgenic X. laevis system as a platform for studying the mechanisms underlying inherited retinal degenerations, especially those caused by rhodopsin mutations and shaped by gene–environment interactions. His broader research interests include rod outer segment assembly and function, with studies involving rhodopsin, prominin-1, cdhr1, ELOVL4, guanylate cyclase, prph2 and related proteins.
