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- W3200302414 abstract "Homeoproteins are transcription factors that are defined by their homeodomain and that play an essential role in establishing the body pattern. One such homeoprotein is OTX2. As other homeoproteins, in addition to cell autonomous activity, OTX2 can transfer between cells and exert non-cell autonomous activities.Previous studies demonstrated that OTX2 has neuroprotective effect on adult retinal cells. OTX2 promotes the survival of adult retinal ganglion cells in-vitro and protects them against N-Methyl-d-aspartate (NMDA) toxicity in vivo, an adult model of glaucoma. Also, when Otx2 is conditionally knocked out in retinal pigmented epithelium cells, this causes photoreceptor degeneration. And expression in retinal pigmented epithelium cells is sufficient for photoreceptors survival, showing that OTX2 in retinal pigmented epithelium cells is necessary for photoreceptor survival. However, it is not known if non-cell autonomous OTX2 transfer from retinal pigmented epithelium to photoreceptors has protective effect on photoreceptors.The objective of this thesis is to characterize the non-cell autonomous activity of OTX2 in the retina in terms of visual function and photoreceptor survival. In the first part we blocked the transfer of OTX2 in the retina and assessed visual function using PVCre::scFvOtx2 mice in which parvalbumin-expressing cells secrete an anti-OTX2 single chain antibody (OTX2scFv). The secreted OTX2scFv blocks OTX2 transfer within the retina with no effect on the retinal structure and anatomy. However, PVCre::scFvOtx2 mice have reduced visual acuity and altered inner retinal physiology demonstrating a non-cell autonomous activity for OTX2 on inner retinal function.In the second part we explored if OTX2 also has neuroprotective effect on photoreceptors. We established that OTX2 is present in the interphotoreceptor matrix of WT mice, where photoreceptor outer segments are located. We also found that exogenous OTX2 is able to bind glycosaminoglycans (GAGs) in the interphotoreceptor matrix on retinal fresh frozen sections. We also found that in ex vivo retinas, exogenous OTX2 is able to modulate mitochondrial reactive oxygen species pathway gene to protect retinal cells against oxidative stress.This work demonstrated that non-cell autonomous OTX2 in the retina leads to an alteration in inner retinal cell function and causes the deficit in visual acuity. OTX2 binds to the OS and alters reactive oxygen species pathway genes in the retina. This may help to provide neuroprotection to photoreceptors cells." @default.
- W3200302414 created "2021-09-27" @default.
- W3200302414 creator A5034939844 @default.
- W3200302414 date "2020-02-18" @default.
- W3200302414 modified "2023-09-23" @default.
- W3200302414 title "Non-cellular autonomous neuroptotection by OTX2 in the retina" @default.
- W3200302414 hasPublicationYear "2020" @default.
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