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Basic Science Ophthalmology Research

The Vision Science Research Laboratory

 

The eye is one of the most specialized organs in the human body, allowing humans the ability to interact with their external environment in a highly complex manner. It accomplishes this by processing externally derived cues in the form of light, transforming these stimuli into electrical signals which then travel along visual pathways throughout the brain for interpretation. The intricate regulation of local ocular microenvironments is fundamental to ensuring a clear visual axis—unimpeded light traveling from the tear-corneal interface all the way to the retina.

Dr Jacob Rullo

MD PhD FRCSC

The eye possesses well-regulated intraocular environments, separate from the systemic circulation of the rest of the body. It is filled with low-protein, plasma-like fluid known as the aqueous and vitreous humours. These substances act as specialized microenvironments working to ensure clear vision can be maintained. The constituents of these “humours” are different from plasma, and are 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, but undetectable through classical systemic investigation.

The detection and characterization of these molecules as potential biomarkers of, and therapeutic targets for disease would have monumental potential in understanding disease pathophysiology, and in the development of novel ophthalmic drugs. We currently have identified four distinct 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 area of focus in the Rullo Laboratory.

A unique microenvironment is also present on the external eye surface: the cornea and conjunctiva. The surface of the eye is covered by a mucous membrane which is in constant flux as it is exposed to pathogens and pathogenic debris. How the eye is able to deal with this prodigious amount of antigenic material while remaining 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 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-HLA-matched (human leukocyte antigen) tissue can survive in the eye in the absence of any systemic immune suppression.

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 microbe::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.