FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2786920172> ?p ?o ?g. }

• W2786920172 endingPage "2943" @default.
• W2786920172 startingPage "2923" @default.
• W2786920172 abstract "Human umbilical tissue-derived cells (hUTC or palucorcel) are currently under clinical investigation for the treatment of geographic atrophy, a late stage of macular degeneration, but how hUTC transplantation mediates vision recovery is not fully elucidated. Subretinal administration of hUTC preserves visual function in the Royal College of Surgeons (RCS) rat, a genetic model of retinal degeneration caused by Mertk loss of function. hUTC secrete synaptogenic and neurotrophic factors that improve the health and connectivity of the neural retina. Therefore, we investigated the progression of synapse and photoreceptor loss and whether hUTC treatment preserves photoreceptors and synaptic connectivity in the RCS rats of both sexes. We found that RCS retinas display significant deficits in synaptic development already by postnatal day 21 (P21), before the onset of photoreceptor degeneration. Subretinal transplantation of hUTC at P21 is necessary to rescue visual function in RCS rats, and the therapeutic effect is enhanced with repeated injections. Synaptic development defects occurred concurrently with morphological changes in Müller glia, the major perisynaptic glia in the retina. hUTC transplantation strongly diminished Müller glia reactivity and specifically protected the α2δ-1-containing retinal synapses, which are responsive to thrombospondin family synaptogenic proteins secreted by Müller glia. Müller glial reactivity and reduced synaptogenesis observed in RCS retinas could be recapitulated by CRISPR/Cas9-mediated loss-of-Mertk in Müller glia in wild-type rats. Together, our results show that hUTC transplantation supports the health of retina at least in part by preserving the functions of Müller glial cells, revealing a previously unknown aspect of hUTC transplantation-based therapy.SIGNIFICANCE STATEMENT Despite the promising effects observed in clinical trials and preclinical studies, how subretinal human umbilical tissue-derived cell (hUTC) transplantation mediates vision improvements is not fully known. Using a rat model of retinal degeneration, the RCS rat (lacking Mertk), here we provide evidence that hUTC transplantation protects visual function and health by protecting photoreceptors and preserving retinal synaptic connectivity. Furthermore, we find that loss of Mertk function only in Müller glia is sufficient to impair synaptic development and cause activation of Müller glia. hUTC transplantation strongly attenuates the reactivity of Müller glia in RCS rats. These findings highlight novel cellular and molecular mechanisms within the neural retina, which underlie disease mechanisms and pinpoint Müller glia as a novel cellular target for hUTC transplantation." @default.
• W2786920172 created "2018-02-23" @default.
• W2786920172 creator A5015389384 @default.
• W2786920172 creator A5017962710 @default.
• W2786920172 creator A5022096000 @default.
• W2786920172 creator A5034786361 @default.
• W2786920172 creator A5055517539 @default.
• W2786920172 creator A5070310230 @default.
• W2786920172 creator A5084238072 @default.
• W2786920172 creator A5084351147 @default.
• W2786920172 creator A5089781632 @default.
• W2786920172 date "2018-02-05" @default.
• W2786920172 modified "2023-10-16" @default.
• W2786920172 title "Subretinal Human Umbilical Tissue-Derived Cell Transplantation Preserves Retinal Synaptic Connectivity and Attenuates Müller Glial Reactivity" @default.
• W2786920172 cites W1895565798 @default.
• W2786920172 cites W1942216383 @default.
• W2786920172 cites W1965784873 @default.
• W2786920172 cites W1973041901 @default.
• W2786920172 cites W1973650956 @default.
• W2786920172 cites W1975436727 @default.
• W2786920172 cites W1980147492 @default.
• W2786920172 cites W1984543781 @default.
• W2786920172 cites W1988452935 @default.
• W2786920172 cites W1996609490 @default.
• W2786920172 cites W1998594263 @default.
• W2786920172 cites W2000341893 @default.
• W2786920172 cites W2012935976 @default.
• W2786920172 cites W2019586013 @default.
• W2786920172 cites W2022073599 @default.
• W2786920172 cites W2026147918 @default.
• W2786920172 cites W2031533008 @default.
• W2786920172 cites W2031611126 @default.
• W2786920172 cites W2032990133 @default.
• W2786920172 cites W2038877420 @default.
• W2786920172 cites W2055820698 @default.
• W2786920172 cites W2059524585 @default.
• W2786920172 cites W2059994807 @default.
• W2786920172 cites W2062620004 @default.
• W2786920172 cites W2063889508 @default.
• W2786920172 cites W2065808929 @default.
• W2786920172 cites W2070614858 @default.
• W2786920172 cites W2085166831 @default.
• W2786920172 cites W2090232240 @default.
• W2786920172 cites W2093633691 @default.
• W2786920172 cites W2098622411 @default.
• W2786920172 cites W2101129664 @default.
• W2786920172 cites W2102960635 @default.
• W2786920172 cites W2104228780 @default.
• W2786920172 cites W2114943784 @default.
• W2786920172 cites W2124147311 @default.
• W2786920172 cites W2126161265 @default.
• W2786920172 cites W2126577146 @default.
• W2786920172 cites W2131701641 @default.
• W2786920172 cites W2139402342 @default.
• W2786920172 cites W2145015359 @default.
• W2786920172 cites W2159555560 @default.
• W2786920172 cites W2162590238 @default.
• W2786920172 cites W2167809348 @default.
• W2786920172 cites W2170160409 @default.
• W2786920172 cites W2172265383 @default.
• W2786920172 cites W2188433447 @default.
• W2786920172 cites W2227187219 @default.
• W2786920172 cites W2236139809 @default.
• W2786920172 cites W2236612802 @default.
• W2786920172 cites W2270572800 @default.
• W2786920172 cites W2318035006 @default.
• W2786920172 cites W2320994969 @default.
• W2786920172 cites W2330439121 @default.
• W2786920172 cites W2399117978 @default.
• W2786920172 cites W2606387395 @default.
• W2786920172 cites W2607001239 @default.
• W2786920172 cites W2738996050 @default.
• W2786920172 cites W51237493 @default.
• W2786920172 cites W757278435 @default.
• W2786920172 cites W84919538 @default.
• W2786920172 doi "https://doi.org/10.1523/jneurosci.1532-17.2018" @default.
• W2786920172 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5864147" @default.
• W2786920172 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29431645" @default.
• W2786920172 hasPublicationYear "2018" @default.
• W2786920172 type Work @default.
• W2786920172 sameAs 2786920172 @default.
• W2786920172 citedByCount "26" @default.
• W2786920172 countsByYear W27869201722018 @default.
• W2786920172 countsByYear W27869201722019 @default.
• W2786920172 countsByYear W27869201722020 @default.
• W2786920172 countsByYear W27869201722021 @default.
• W2786920172 countsByYear W27869201722022 @default.
• W2786920172 countsByYear W27869201722023 @default.
• W2786920172 crossrefType "journal-article" @default.
• W2786920172 hasAuthorship W2786920172A5015389384 @default.
• W2786920172 hasAuthorship W2786920172A5017962710 @default.
• W2786920172 hasAuthorship W2786920172A5022096000 @default.
• W2786920172 hasAuthorship W2786920172A5034786361 @default.
• W2786920172 hasAuthorship W2786920172A5055517539 @default.
• W2786920172 hasAuthorship W2786920172A5070310230 @default.
• W2786920172 hasAuthorship W2786920172A5084238072 @default.
• W2786920172 hasAuthorship W2786920172A5084351147 @default.
• W2786920172 hasAuthorship W2786920172A5089781632 @default.

• next