June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Subconjunctival dendrimer-drug therapy for the treatment of corneal inflammation
Author Affiliations & Notes
  • Uri Soiberman
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Siva Pramodh Kambhampati
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Manoj K. Mishra
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Samuel C Yiu
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Abdul Elah Al Towerki
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Walter J. Stark
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Rangaramanujam M. Kannan
    Ophthalmology, Johns Hopkins University, Baltimore, MD
  • Footnotes
    Commercial Relationships Uri Soiberman, None; Siva Pramodh Kambhampati, None; Manoj K. Mishra, None; Samuel Yiu, None; Abdul Elah Al Towerki, None; Walter Stark, None; Rangaramanujam Kannan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5035. doi:
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      Uri Soiberman, Siva Pramodh Kambhampati, Manoj K. Mishra, Samuel C Yiu, Abdul Elah Al Towerki, Walter J. Stark, Rangaramanujam M. Kannan; Subconjunctival dendrimer-drug therapy for the treatment of corneal inflammation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5035.

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

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Abstract
 
Purpose
 

To assess whether subconjunctivally administered dendrimers target activated corneal macrophages, and also whether subconjunctival dendrimer-dexamethasone (D-Dex) conjugate is efficacious in the treatment of corneal alkali burn.

 
Methods
 

A rat animal model of corneal alkali burn was used by exposure to 1N NaOH solution. 48 hours following the alkali burn, subconjunctival treatment was administered with either dendrimer-Cy5 (D-Cy5; to assess corneal macrophage uptake), or D-Dex (therapy). The rats were assessed for corneal edema, corneal opacity and development of corneal neovascularization (NV). Central corneal thickness (CCT) was assessed with anterior segment optical coherence tomography (OCT). The rats were sacrificed 7 days after the alkali burn and the corneas were cross sectioned and then prepared for histological assessment and confocal microscopy.

 
Results
 

Alkali burn led to increased macrophage accumulation, corneal thickness, opacity and edema in the central cornea. D-Cy5 was selectively co-localized with the corneal macrophages in the central cornea. D-Dex treatment resulted in favorable outcomes with reduced CCT and edema, fewer central corneal macrophages and improved corneal clarity compared to untreated controls. Corneal NV was assessed one week following alkali burn: the D-Dex treated eyes had reduced corneal NV (1.5±1.2 quadrants) as opposed to untreated eyes (4±0 quadrants) (p=0.02). Eyes treated with D-Dex did not have elevated intraocular pressures compared with controls.

 
Conclusions
 

This short-term pilot study conducted in rats demonstrates that dendrimers can target macrophages and be retained in them for up to one week following alkali burn to the central cornea. It also showed that when treated with D-Dex, the CCT was lower than in untreated control eyes. Additionally, the amount of corneal neovascularization was lower in D-Dex treated eyes. These findings suggest that dendrimers may be a potential drug delivery platform in inflammatory ocular surface disorders especially because they target immune effector cells.  

 
Numerous large mononuclear inflammatory cells are dispersed throughout the central cornea. The majority of these cells are stained by anti-IBA-1 and lectin which suggests that they are indeed macrophages.
 
Numerous large mononuclear inflammatory cells are dispersed throughout the central cornea. The majority of these cells are stained by anti-IBA-1 and lectin which suggests that they are indeed macrophages.
 
 
Changes in central corneal thickness following treatment (microns).
 
Changes in central corneal thickness following treatment (microns).

 
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