July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Targeted delivery of dendrimer-triamcinolone acetonide modulates neuroinflammation and attenuates neovascularization in oxygen-induced retinopathy
Author Affiliations & Notes
  • Hongkwan Cho
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Siva Pramodh Kambhampati
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Michael Lai
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Grace Lee
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Lingli Zhou
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Kannan Rangaramanujam
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Elia J Duh
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Hongkwan Cho, None; Siva Pramodh Kambhampati, None; Michael Lai, None; Grace Lee, None; Lingli Zhou, None; Kannan Rangaramanujam, Ashvattha Therapeutics,LLC (I); Elia Duh, None
  • Footnotes
    Support  This work was supported by funds from NIH EY001765 (Core), EY022683 (EJD), EY025304 (RK) and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3367. doi:
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      Hongkwan Cho, Siva Pramodh Kambhampati, Michael Lai, Grace Lee, Lingli Zhou, Kannan Rangaramanujam, Elia J Duh; Targeted delivery of dendrimer-triamcinolone acetonide modulates neuroinflammation and attenuates neovascularization in oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3367.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Growing evidence indicates that activation of microglia and associated neuroinflammation play an essential role in the pathogenesis of multiple retinal diseases, including ischemic retinopathies. Therapeutic strategies targeting the activated microglia to attenuate neuroinflammation could be a viable treatment option for these diseases. The corticosteroid triamcinolone is well-known for its anti-inflammatory and anti-angiogenic properties, but also has known ocular side effects. The objective of this study was to utilize dendrimer-based drug delivery of triamcinolone acetonide (TA) to target activated retinal microglia/macrophages in the mouse oxygen-induced retinopathy (OIR) model.

Methods : C57BL/6J mice were subjected to hyperoxia at 75% oxygen for 5 days from postnatal day (P)7 through P12. At P15, mice were treated with either Free-TA (0.5ug), dendrimer-TA (0.5ug) conjugate (D-TA), or Cy5-labeled dendrimer (D-Cy5) in one eye via intravitreal injection. The contralateral eyes were injected with PBS as controls. Studies investigating co-localization of D-Cy5 with microglia (IBA-1 staining), inflammatory gene expression (qRT-PCR), and percent of neovascular tuft area (lectin) were performed at P17.

Results : Retinal flat mount images showed co-localization of D-Cy5 with microglia in the superficial layer as well as in the deeper layer at P17. D-TA treatment significantly (p<0.05) suppressed the expression of inflammatory mediators: TNF-alpha, CCL2, IL-1beta, and CXCL2 as compared with PBS-treated contralateral eyes. Mice injected with the same amount of Free-TA did not show such suppression. The area of neovascular tuft was significantly (p<0.005) attenuated in the D-TA injected eyes while the Free-TA injected eyes showed no difference when compared with PBS-treated control eyes.

Conclusions : The results from this study suggest that an activated microglia/macrophage-specific uptake of D-TA in the retina which correlated with suppression of inflammatory gene expression and neovascular tufts formation. Importantly, the same amount of free-TA did not show any therapeutic benefits, indicating the importance of microglia-specific drug delivery in the retina. Dendrimer-based drug delivery could therefore be a potential therapeutic option for ischemic retinopathies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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