Abstract Title

Modulation of the Retinal Immune Environment in a Zebrafish System of Rod Photoreceptor-Specific Degeneration

Additional Funding Sources

The project described was supported by a University of Idaho Summer Undergraduate Research Fellowship made possible by a 2017-2018 Undergraduate Research Grant from the Higher Education Research Council/Idaho State Board of Education and The Mitchell Lab at The University of Idaho.

Abstract

Activated and pro-inflammatory microglia, along with accompanying local inflammation, are associated with human retinal degenerative disease. However, it remains unclear if these aspects of the immune response are symptomatic or directly initiate and/or contribute to disease pathology, such as the death of additional retinal neurons. One theory for continued loss of neurons in retinal degenerative disease is that microglia may engulf, or possibly initiate cell death of, otherwise healthy neurons. Our project attempts to test this theory using a zebrafish system in which rod photoreceptors die due to a toxic transgene (XOPS:mCFP), but cone photoreceptors survive. We first characterized microglial characteristics in XOPS:mCFP retinas compared to wildtype and found that microglia localize to the photoreceptor layer and engulf dying rods, but total numbers of microglia are similar. Next, we successfully induced a pro-inflammatory retinal immune environment by intraocular injection of zymosan (a pro-inflammatory compound), as indicated by infiltration and division of immune cells in the retina and gene expression of selected transcripts. Our next goal is to determine if this induction of a pro-inflammatory retinal environment may result in subsequent cone death or disappearance in XOPS:mCFP retinas, thus directly probing contributions of a dysregulated immune environment to retinal degenerative disease.

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Modulation of the Retinal Immune Environment in a Zebrafish System of Rod Photoreceptor-Specific Degeneration

Activated and pro-inflammatory microglia, along with accompanying local inflammation, are associated with human retinal degenerative disease. However, it remains unclear if these aspects of the immune response are symptomatic or directly initiate and/or contribute to disease pathology, such as the death of additional retinal neurons. One theory for continued loss of neurons in retinal degenerative disease is that microglia may engulf, or possibly initiate cell death of, otherwise healthy neurons. Our project attempts to test this theory using a zebrafish system in which rod photoreceptors die due to a toxic transgene (XOPS:mCFP), but cone photoreceptors survive. We first characterized microglial characteristics in XOPS:mCFP retinas compared to wildtype and found that microglia localize to the photoreceptor layer and engulf dying rods, but total numbers of microglia are similar. Next, we successfully induced a pro-inflammatory retinal immune environment by intraocular injection of zymosan (a pro-inflammatory compound), as indicated by infiltration and division of immune cells in the retina and gene expression of selected transcripts. Our next goal is to determine if this induction of a pro-inflammatory retinal environment may result in subsequent cone death or disappearance in XOPS:mCFP retinas, thus directly probing contributions of a dysregulated immune environment to retinal degenerative disease.