Fatty Acid Binding Proteins Facilitate Reprogramming of Müller Glia into Progenitor Cells

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Degenerative retinal diseases result in neuronal cell death, which causes in permanent vision loss in humans. The response to the loss of retinal neuron across species is diverse, with some species capable of complete and functional retinal regeneration. One source of these regenerated neurons is Müller glia (MG), the primary glial cell of the retina. In zebrafish, MG respond to damage by dedifferentiating into progenitor cells (MGPCs) which proliferate before they undergo neurogenesis. While mice completely lack a regenerative response by MG, chick MG form progenitors with limited neurogenesis, proving to be an effective phenotype for understanding molecular pathways that influence reprogramming and cell fate. Preliminary data has indicated that fatty acid binding protein 8 (FABP8) is highly upregulated early in the regenerative response to damage in the chick retina. FABPs are a class of lipid binding proteins that traffic polyunsaturated fatty acids such as docosahexaenoic acid and arachidonic acid which have been collectively implicated in signal transduction, neurotransmission, proliferation, differentiation, and neuronal migration. We hypothesize that FABP8 is significantly influencing the early reprogramming phase of MG, and can be utilized to drive the formation of MGPCs in mammalian retinas. To test this hypothesis, we will first characterize the spatiotemporal expression pattern of FABP8 in damaged and growth factor treated chick retinas. Subsequently, we will test the effect of new and established pharmacological inhibitors of FABP proteins on the formation of retinal progenitors in chick. Single cell sequencing identified FABP5, FABP7, and FABP8 as significantly increasing in Müller glia after NMDA damage. FABP8 mRNA expression correlated to protein localization in Müller glia after damage. Pan inhibitor of FABPs BMS309403 was found to significantly reduce the formation of progenitor cells. Further research into the potential role of endocannabinoids and FABPs is being evaluated in the mechanism of action for affecting Müller glia’s reprogramming response.


Biological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)


Retina, Reprogramming, Muller Glia, Cellular Neuroscience, Single Cell RNA Sequencing