Protective effects of sustained transscleral unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats

Nobuhiro Nagai, Satoru Iwata, Hirokazu Kaji, Kaori Sampei, Yuki Katsukura, Hideyuki Onami, Matsuhiko Nishizawa, Toru Nakazawa, Yukihiko Mashima, Toshiaki Abe

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices. Retinal thickness was evaluated by histological examination. Western blots of specimens 4 weeks after implantation were performed. ERGs showed that the UNO-loaded device prevented the reduction of ERG amplitudes 2 and 4 weeks after implantation, compared with results using a placebo device or topical application. Histological examination showed that the UNO-loaded device prevented the reduction of retinal thickness, and Western blots of specimens indicated that the UNO-loaded device decreased expression of ERK1/2, phosphorylated ERK1/2, and caspase-3. A device that provided sustained UNO administration protected against retinal degeneration in rhodopsin mutant rats, and thus, may have translational potential as a sustainable method to administer drugs to treat retinitis pigmentosa.

Original languageEnglish
Pages (from-to)1730-1737
Number of pages8
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
Volume104
Issue number8
DOIs
Publication statusPublished - 2016 Nov 1

Keywords

  • poly(ethyleneglycol) dimethacrylate
  • retina
  • retinitis pigmentosa
  • transscleral drug delivery
  • unoprostone

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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