Using models of viral infection to further our understanding of immune responses in the eye

Martin Sebastian Zinkernagel

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated] To date little information is available on how the immune system deals with viral pathogens in the eye and especially in the retina. Yet, viruses such as cytomegaloviruses (CMV) can cause retinitis which in turn can lead to blindness.
In response to this knowledge gap, the research project which forms the basis for this PhD thesis sought to gain a better understanding of how the immune system reacts to virus present in the eye, and to investigate whether a systemic viral infection influences the eye’s micro-environment.
Chapter 2 describes novel imaging techniques in common laboratory animal species, laying the foundation for assessing ocular pathology in experimental animal models. This chapter demonstrates that retinal morphology can be assessed in a noninvasive manner using techniques such as scanning laser ophthalmoscopy and optical coherence tomography. These techniques are especially suited to monitoring disease progression or treatment efficacy sequentially over time as illustrated in Chapter 3. In Chapter 3, I tested how murine cytomegalovirus (MCMV) infection of the eye can be tracked in vivo with a scanning laser ophthalmoscope, in the same animal over time. This novel technique allows noninvasive monitoring of infectious agents in the eye and therefore may contribute to improving our knowledge of the course and pathogenesis of intraocular infections. This is the first report that describes how an ocular pathogen can be tracked in vivo.
In Chapter 4 flow cytometry was used to analyze the lymphocytic T cell response after experimental subretinal infection with MCMV. To date, flow cytometry in ocular tissue had been rarely used due to the small number of ocular cells that could be acquired from a murine eye. I optimized retinal flow cytometry protocols and achieved high cell yields and exploitable cell numbers from individual mouse retina.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2012

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