Dr. Sivak's laboratory is investigating the molecular pathways directing cellular responses to tissue damage and repair in the eye. This work has direct relevance to retinal degenerative diseases, and also serves as a model for these mechanisms in the central nervous system and other organs. His lab has recently turned its attention to damage of the inner retinal layers and optic nerve. Injury to these tissues drives the pathologic outcome for patients with glaucoma; a leading cause of vision loss and blindness in Canada and worldwide. Dr. Sivak is focusing on the roles that metabolic, oxidative, and biomechanical stress place on the sensitive retinal ganglion cells and their associated glia. For these experiments he uses a variety of molecular, cellular, and genetic techniques.
Industry Expertise (3)
Areas of Expertise (9)
Glaucoma Research Chair (professional)
Appointed by the Krembil Research Institute (Krembil).
Tufts University: Ph.D., Cell, Molecular, & Developmental Biology 2002
McGill University: B.S., Biology 1996
- Optometric Glaucoma Society
Biomechanical insult contributes to many chronic pathological processes, yet the resulting influences on signal transduction mechanisms are poorly understood. The retina presents an excellent mechanotransduction model, as mechanical strain on sensitive astrocytes of the optic nerve head (ONH) is intimately linked to chronic tissue remodeling and excavation by matrix metalloproteinases (MMPs), and apoptotic cell death. However, the mechanism by which these effects are induced by biomechanical strain is unclear. We previously identified the small adapter protein, PEA-15 ...
HLA-B27 is a major histocompatibility complex class I (MHCI) allele that has been closely associated with the development of ankylosing spondylitis and acute anterior uveitis (AAU), the most common form of uveitis worldwide. We have been characterizing the phenotypes of transgenic mice carrying a human HLA-B27 allele, but that are deficient in endogenous mouse MHCI genes (H-2K(-/-) and H-2D(-/-) double knockout, or DKO) to create the HLA-B27/DKO line. In maintaining and expanding this colony, we observed a rare sporadic severe central keratitis that developed in transgenic animals, but that was not present in wild-type (WT) animals
Gene therapy could offer improvement in the treatment of glaucoma compared to the current standard of lowering intraocular pressure. We have developed and characterized non-viral gemini surfactant-phospholipid nanoparticles (GL-NPs) for intravitreal and topical administration.
Retinal ganglion cells (RGCs), used as a common model of central nervous system injury, are particularly vulnerable to metabolic and oxidative damage. However, molecular mechanisms underlying this sensitivity have not been determined in vivo.
Astrocytes are the most abundant glial cell in the retinal nerve fiber layer (NFL) and optic nerve head (ONH), and perform essential roles in maintaining retinal ganglion cell (RGC) detoxification and homeostasis. Mature astrocytes are relatively quiescent, but rapidly undergo a phenotypic switch in response to insult, characterized by upregulation of intermediate filament proteins, loss of glutamate buffering, secretion of pro-inflammatory cytokines, and increased antioxidant production. These changes result in both positive and negative influences on RGCs. However, the mechanism regulating these responses is still unclear, and pharmacologic strategies to modulate select aspects of this switch have not been thoroughly explored. Here we describe a system for rapid culture of mature astrocytes from the adult rat retina that remain relatively quiescent