Subconjunctival dendrimer-drug therapy for the treatment of dry eye in a rabbit model of induced autoimmune dacryoadenitis

Hui Lin, Ying Liu, Siva P. Kambhampati, Chih Chien Hsu, Rangaramanujam M. Kannan, Samuel C. Yiu

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To investigate the efficacy of a single subconjunctival injection of dendrimer-dexamethasone conjugate in a rabbit model of induced autoimmune dacryoadenitis (AID). Methods: Dendrimer biodistribution after subconjunctival injection in AID animals was evaluated using Cy5-labelled dendrimer (D-Cy5) and confocal microscopy. Diseased animals were treated with free dexamethasone (Free-Dex), dendrimer-dexamethasone (D-Dex), or saline via a single subconjunctival injection. The efficacy was evaluated using various clinical evaluations, such as Schirmer's test, tear breakup time (TBUT), and fluorescein and rose Bengal staining. Histopathology was evaluated by H&E staining and immunostaining. Levels of inflammatory cytokines and aquaporin proteins in the LGs were determined by real-time PCR. Results: Subconjunctivally administered dendrimers selectively localized in the inflamed LGs, and were taken up by the infiltrating cells. At two weeks post single dose-treatment, the D-Dex group showed improved clinical evaluations. No significant changes were observed in other groups. H&E staining demonstrated less inflammatory cell infiltration and fewer atrophic acini in D-Dex group, compared to those treated with saline or Free-Dex. Immunohistochemistry demonstrated that the intensity of CD-18 (+) and RTLA (+) was weaker in LGs in the D-Dex group than in other treatment groups. Pro-inflammatory gene expression levels of MMP9, IL6, IL8, and TNFα were significantly decreased in the D-Dex group compared to the Free-Dex and saline group. Conclusions: The dendrimer exhibits pathology-dependent biodistribution in the inflamed LGs. Subconjunctivally administered D-Dex suppressed LG inflammation, leading to partial recovery of LG function with clinical improvement in induced AID. Sjögren's patients may benefit from this targeted nanomedicine approach.

Original languageEnglish (US)
Pages (from-to)415-423
Number of pages9
JournalOcular Surface
Volume16
Issue number4
DOIs
StatePublished - Oct 2018

Keywords

  • Autoimmune dacryoadenitis
  • Dendrimer
  • Dexamethasone
  • Dry eye
  • Sjögren's syndrome
  • Subconjunctival injection

ASJC Scopus subject areas

  • Ophthalmology

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