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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Article
  • Peer Reviewed
UC Irvine Previously Published Works (2007)

To evaluate the efficacy of intravitreal injection of GDNF-loaded biodegradable microspheres in promoting the survival of retinal ganglion cells (RGCs) and their axons in a rat model of chronically elevated intraocular pressure (IOP).

Chronic elevation of IOP was induced in Brown Norway rats through injection of hypertonic saline (1.9 M) into the episcleral veins. After injection, IOP was measured twice a week in rats using topical anesthesia. Poly DL-lactide-co-glycolide (PLGA) microspheres were fabricated using a modified version of the spontaneous emulsification technique. Two and ten percent of volume solutions of microspheres loaded with glial cell line-derived neurotrophic factor (GDNF) were injected into the vitreous cavity of rats with elevated IOP, with injections of blank microspheres and PBS serving as controls. Histological analysis was used to quantify surviving RGCs and axons and provide comparison among different groups. In addition, the thickness of the retinal inner plexiform layer (IPL) and the level of glial fibrillary acidic protein (GFAP) expression within the retina and optic nerve were quantitatively compared.

IOP was significantly increased in eyes with episcleral vein injection over untreated eyes (p<0.001) but did not show a significant difference among groups that received intravitreal injections of GDNF microspheres, blank microspheres, or PBS (p=0.1852). The duration of IOP elevation in this experiment was eight weeks. Expression of GDNF and its receptors localizes to the adult rat RGCs. Ten percent of the GDNF microsphere treatment significantly increased RGC survival and axon survival (p<0.001), reduced the loss of retinal IPL thickness (p<0.001), and decreased glial cell activation in the retina and optic nerve (p<0.001) compared with blank microspheres and PBS. In addition, GDNF microsphere treatment moderately reduced cupping of the optic nerve head.

Delivery of GDNF via biodegradable microspheres significantly increased the survival of RGCs and their axons, preserved IPL thickness, and decreased retina and optic nerve glial cell activation in an experimental glaucoma model. This study suggests that GDNF delivered by PLGA microspheres may be useful as a neuroprotective tool in the treatment of glaucomatous optic neuropathy.

    Cover page: Intravitreal injections of GDNF-loaded biodegradable microspheres are neuroprotective in a rat model of glaucoma.
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2016)
    Accurate and precise annotation of 3' UTRs is critical for understanding how mRNAs are regulated by microRNAs (miRNAs) and RNA-binding proteins (RBPs). Here, we describe a method, poly(A) binding protein-mediated mRNA 3' end retrieval by crosslinking immunoprecipitation (PAPERCLIP), that shows high specificity for mRNA 3' ends and compares favorably with existing 3' end mapping methods. PAPERCLIP uncovers a previously unrecognized role of CstF64/64tau in promoting the usage of a selected group of non-canonical poly(A) sites, the majority of which contain a downstream GUKKU motif. Furthermore, in the mouse brain, PAPERCLIP discovers extended 3' UTR sequences harboring functional miRNA binding sites and reveals developmentally regulated APA shifts, including one in Atp2b2 that is evolutionarily conserved in humans and results in the gain of a functional binding site of miR-137. PAPERCLIP provides a powerful tool to decipher post-transcriptional regulation of mRNAs through APA in vivo.
      Cover page: PAPERCLIP Identifies MicroRNA Targets and a Role of CstF64/64tau in Promoting Non-canonical poly(A) Site Usage
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