Iron-chelating drugs enhance cone photoreceptor survival in a mouse model of retinitis pigmentosa

Ke Wang, Bo Peng, Jia Xiao, Orly Weinreb, Moussa B.H. Youdim, Bin Lin

Research output: Journal article publicationJournal articleAcademic researchpeer-review

12 Citations (Scopus)

Abstract

PURPOSE. Retinitis pigmentosa (RP) is a group of hereditary retinal degeneration in which mutations commonly result in the initial phase of rod cell death followed by gradual cone cell death. The mechanisms by which the mutations lead to photoreceptor cell death in RP have not been clearly elucidated. There is currently no effective treatment for RP. The purpose of this work was to explore iron chelation therapy for improving cone survival and function in the rd10 mouse model of RP. METHODS. Two iron-chelating drugs, 5-(4-(2-hydroxyethyl) piperazin-1-yl (methyl)-8-hydroxyquinoline (VK28) and its chimeric derivative 5-(N-methyl-N-propargyaminomethyl)-quinoline- 8-oldihydrochloride (VAR10303), were injected intraperitoneally to rd10 mice every other day starting from postnatal day 14. We investigate the effects of the two compounds on cone rescue at three time points, using a combination of immunocytochemistry, RT-PCR, Western blot analysis, and a series of visual function tests. RESULTS. VK28 and VAR10303 treatments partially rescued cones, and significantly improved visual function in rd10 mice. Moreover, we showed that the neuroprotective effects of VK28 and VAR10303 were correlated to inhibition of neuroinflammation, oxidative stress, and apoptosis. Furthermore, we demonstrated that downregulation of NF-kB and p53 is likely to be the mechanisms by which proinflammatory mediators and apoptosis are reduced in the rd10 retina, respectively. CONCLUSIONS. VK28 and VAR10303 provided partial histologic and functional rescue of cones in RD10 mice. Our study demonstrated that iron chelation therapy might represent an effective therapeutic strategy for RP patients.
Original languageEnglish
Pages (from-to)5287-5297
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number12
DOIs
Publication statusPublished - 1 Oct 2017

Keywords

  • Iron-chelating drugs
  • Microglia
  • Photoreceptors
  • Rd10 mice
  • Vision rescue

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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