April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Corneal Nerve Imaging As A Biomarker For Paclitaxel-induced Peripheral Neuropathy
Author Affiliations & Notes
  • Giulio Ferrari
    Ophthalmology - Cornea Unit, San Raffaele University Scientific Instute, Milan, Italy
  • Nambi Nallasamy
    Harvard Medical School, Schepens Eye Research Institute, Boston, Massachusetts
  • Heather Downs
    Harvard Medical School,
    Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts
  • Reza Dana
    MEEI/SERI Harvard Ophthalmology, Boston, Massachusetts
  • Anne Louise Oaklander
    Nerve Injury,
    Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Giulio Ferrari, None; Nambi Nallasamy, None; Heather Downs, None; Reza Dana, None; Anne Louise Oaklander, None
  • Footnotes
    Support  Bietti Eye Foundation
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 293. doi:
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      Giulio Ferrari, Nambi Nallasamy, Heather Downs, Reza Dana, Anne Louise Oaklander; Corneal Nerve Imaging As A Biomarker For Paclitaxel-induced Peripheral Neuropathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):293.

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

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Purpose: : Small-fiber polyneuropathies (SFPN) are an increasingly common cause of chronic pain and sensory loss from common conditions including diabetes, HIV, and neurotoxicity. We used a common and dose-limiting cancer chemotherapeutic agent, paclitaxel, to evaluate the potential of measuring corneal innervation to assess presence and severity of SFPN. Parallel assessment of epidermal innervation was also made from distal-limb skin biopsies, which is the current standard diagnostic method and provided positive controls.

Methods: : 6 week-old male C57/BL6 mice (n=10; 10; 16 respectively) were administered paclitaxel at 5, 10, or 20mg/kg given as one intraperitoneal dose. C57/BL6 untreated mice (n=14) provided controls. Mice were sacrificed 2 weeks later; tissues harvested for immunohistochemistry comprised 2 mm punch skin-biopsies from their hind paws, corneas and trigeminal ganglia. After fixation and sectioning, skin-biopsies and ganglia were immunolabeled against PGP 9.5, the standard marker used for clinical diagnosis of small-fiber polyneuropathy. Corneal axons were labeled with anti-beta-3 tubulin antibody. Epidermal nerve fibers (ENF) were quantitated by a single blinded morphometrist using consensus methods for clinical diagnosis, and the total length of all corneal axons was digitally measured using an automated Matlab-based program. Trigeminal ganglia sections were qualitatively assessed for gross anatomic difference between groups. ANOVA was used to evaluate differences between groups.

Results: : Skin biopsies revealed expected dose-responsive losses of ENF (P<0.0001) as did corneal samples (P<0.0001). The ganglia showed a similar pattern of neural body rarefaction.

Conclusions: : This study suggests that the SFPN caused by paclitaxel chemotherapy affects corneal as well as distal-limb innervation in mice. Not only presence, but severity of SFPN was detectable in the cornea; post-hoc analysis found significantly different corneal-nerve densities between all dosage groups (P<0.0001). Given the increasing availability of non-invasive and repeatable clinical examination of humans by in-vivo corneal confocal microscopy, corneal nerve assessments might provide a valuable new tool with which to evaluate small-fiber polyneuropathies.

Keywords: microscopy: confocal/tunneling • cornea: epithelium • drug toxicity/drug effects 

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