I was bitten by the science bug early in life. Inserting lines into the mouse jugular vein and modeling leukocyte recruitment in animal models of disease as a high school student in 2001, exposed me to the world of research and to the concept of inflammation; a fundamental disease process. I continued to perform basic science research as an undergraduate student at McMaster University. Subsequently, I entered the MD/PhD program at the University Toronto in 2006. My research focus was on charactering what makes white blood cells unique in their ability to stick down while resisting the detaching forces of flowing blood. I became very interested here in various forms of microscopy and live cell imaging of leukocytes. My microscopy focus and desire to visualize physiology in real time led me to the field of ophthalmology. From 2015 to 2020, I concurrently completed my ophthalmology residency and a post-doctoral fellowship at Queen’s University. My research focus over the past five years has been characterizing differences in the ocular microenvironment with respect to the discovery of novel biomolecules/biomarkers, understanding intraocular immune mechanisms and the immune biology of the external ocular surface. I started as a new faculty member at Queen’s University in the Departments of Ophthalmology and Biomedical and Molecular Sciences in July 2020.
The eye is one of the most specialized organs in the human body. The eye allows humans the ability to interact with their external environment in a highly complex manner. In order to do so, the eye processes externally derived cues in the form of light and transforms these stimuli into electrical signals, which then travel along visual pathways throughout the brain for interpretation. The intricate regulation of local ocular microenvironments are fundamental to ensuring a clear visual axis; unimpeded light traveling from the tear-corneal interface all the way to the retina.
The eye possesses well-regulated intraocular environments, separate from the systemic circulation, filled with low-protein, plasma-like fluid, known as the aqueous and vitreous humours. These substances contained within the eye act as specialized microenvironments to ensure clear vision can be maintained. The constituents of these “humours” are different from plasma and regulated by well controlled blood ocular barriers. Under conditions of disease, these microenvironments undergo states of disequilibrium resulting in local changes in small biomolecules within these compartments, but not detected through classical systemic investigation. The detection and characterization of these molecules as potential biomarkers of disease and therapeutic targets would have monumental potential in understanding disease pathophysiology and in the development of novel ophthalmic drugs. We currently have identified four unique biomolecule targets which preferentially accumulate in human eyes and exhibit unique profiles under states of disease. Understanding how these targets interplay in the pathophysiology of neuro-retinal degenerative disease, their potential to act as biomarkers and ability to be manipulated as a therapeutic target are one of the areas of focus in the Rullo Laboratory.
A unique microenvironment is also present on the external eye surface, namely the cornea and conjunctiva. The surface of the eye is covered by a mucous membrane which is in constant flux being exposed to pathogens and pathogenic debris. How the eye is able to deal with this prodigious amount of antigenic material yet remain quiescent is a fundamental process for the eye. In fact, the eye must be capable of modulating both local and systemic immune responses in order to keep the eye free from inflammatory pathways that may damage vision-generating structures. For over a century it has been long known the eye is an immune privileged site; capable of reduced immune responses to both allo- and auto-genic material. The practice of corneal transplantation is an excellent example of how non-human leukocyte antigen matched tissue can survive in the eye in the absence of any systemic immune suppression. Yet, in contrast, exposing the surface of the eye to microbial by-products and immunogenic agents can protect mammals from downstream respiratory-tract virus induced disease. The eye therefore acts as a site capable of inducing systemic immunity that both regulates anti- and pro-inflammatory pathways, ultimately to protect itself from damage. This novel immune-inductive, microbe enriched site has enormous potential for understanding how the local environments of the eye can shape our systemic landscape. We have begun to characterize the importance of native ocular surface microbial:host interactions in the context of disease initiation in patients, the role of microbial environments on intraocular disease and more recently how the eye may be used as a site to model host:pathogen interactions and shape protective systemic immune responses.
These observations and concepts are currently under study by Dr. Jacob Rullo in the Vision Science Research Laboratory.
Rullo J, Mehraban Far P, Quinn M, Sharma N, Bae S, Sharma S. Local oral and nasal microbiome diversity in age-related macular degeneration. Scientific Reports. 2020. Mar 2; 10(1):3862
Rullo J, Pennimpede T, Mehraban Far P, Strube Y, Irrcher I, Urton T, Bona M, Gonder T, Campbell R, ten Hove M, Sharma S, Farmer J, Petkovich M. Intraocular Calcidiol: Uncovering a role for vitamin D in the eye. Journal of Steroid Biochemistry and Molecular Biology. 2020. Mar; 197:105536
Rullo J, Bae S, Mehraban Far P, Hazimi AA, Gupta V, Bal M, Hopman W, Irrcher I, Urton T, Bona M, Campbell R, Gonder T, Sharma S. Intraocular antibodies as a novel target for understanding and treating vascular diseases of the eye. Canadian Journal of Ophthalmology. 2020. Jun; 55(3): 263-271.
Becker H, Rullo J, Chen M, Ghazarian M, Bak S, Xiao H, Hay J, Cybulksy MI. α1β1 Integrin-Mediated Adhesion Inhibits Macrophage Exit from a Peripheral Inflammatory Lesion. Journal of Immunology. 2013 Apr 15;190(8):4305-4314
Rullo J, Becker H, Hyduk SJ, Wong J, Digby G, Cano AP, Hartwig J, Cybulsky MI. Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion. Journal of Cell Biology. 2012 Apr 2;197(1):115-129