June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Keeping an Eye on Molecular Imaging: Assessment of Drug Toxicity in Small Ocular Structure using Mass Spectrometry Imaging
Author Affiliations & Notes
  • Gregory Hamm
    MS Imaging, ImaBiotech, Loos, France
  • Françoise Baudouin
    U968, INSERM, Paris, France
    UMR_S 968, Institut de la Vision, UPMC Univ Paris 06, Paris, France
  • Nicolas desbenoit
    U968, INSERM, Paris, France
    UMR_S 968, Institut de la Vision, UPMC Univ Paris 06, Paris, France
  • Hong Liang
    U968, INSERM, Paris, France
    UMR_S 968, Institut de la Vision, UPMC Univ Paris 06, Paris, France
  • Olivier Laprevote
    Univ Paris Descartes, Paris, France
  • Alain Brunelle
    Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France
  • Jonathan Stauber
    MS Imaging, ImaBiotech, Loos, France
  • Christophe Baudouin
    UMR_S 968, Institut de la Vision, UPMC Univ Paris 06, Paris, France
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
  • Footnotes
    Commercial Relationships Gregory Hamm, None; Françoise Baudouin, None; Nicolas desbenoit, None; Hong Liang, None; Olivier Laprevote, None; Alain Brunelle, None; Jonathan Stauber, None; Christophe Baudouin, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5691. doi:https://doi.org/
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      Gregory Hamm, Françoise Baudouin, Nicolas desbenoit, Hong Liang, Olivier Laprevote, Alain Brunelle, Jonathan Stauber, Christophe Baudouin; Keeping an Eye on Molecular Imaging: Assessment of Drug Toxicity in Small Ocular Structure using Mass Spectrometry Imaging. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5691. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

Mass spectrometry Imaging (MSI) applications to ophthalmic drug discovery have recently gained growing interest especially for preclinical studies in pharmacology or toxicology. In our study, MSI was applied to assess the distribution of Benzalkonium chloride (BAK) compound (antiglaucoma eye drops preservative) in specific areas of the eye after instillation in animal model and human tissues. They have been reported to cause ocular surface disorders with tear film alteration, eye irritation and to promote dry eye. The distribution of BAK compoundwas investigated in small specific histological regions of the eye (such as iridocorneal angle or sclera, choroid, retina regions) in order to estimate efficiency of action or adverse effects of the treatment.

 
Methods
 

The eyes of New Zealand rabbits were instilled with different BAK solutions at 0.01%, 2 drops BID for 1 month or 5 months or 0.2% at 1 drop/day for 1 month. After sacrifice, eyes were quickly enucleated and embedded in tragacanth gum and frozen at -80°C. Serial cryosections were deposited on glass slides for Hematoxylin-eosin staining or immunohistochemistry (IHC) and conductive glass slide for mass spectrometry imaging.

 
Results
 

High spatial resolution images were performed at cells level (30 µm). Local Drug concentration differences were observed according to histological area and position on the eye section (anterior, posterior, temporal or nasal side).The figure below shows an optical image of H&E staining of rabbit eye 1 month after start of treatment (left) and the distribution of the two benzalkonium ions (Red & Green images, right). MSI and IHC results were put side by side to correlate inflammatory areas (degradation of CSE or apoptosis phenomena within cornea/conjonctiva region) with BAK localization. Moreover, a high accumulation of BAKs were observed at the sclerocorneal junction and near trabecular meshwork involved in aqueous humor outflow. Moreover, differential analysis was carried out to find disease state biomarkers of each ocular structure.

 
Conclusions
 

MSI offers new insight in ocular therapeutic/pharmaceutical research, especially to give a better understanding of the drug candidate migration from the front to the back of the eye to assist drug efficiency or toxicity studies for specific tissue targeting eye diseases.  

 
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