Ocular Surface Changes Differ Significantly Between Oxaliplatin- and Diabetes-Induced Polyneuropathy

Martin Schicht1, Marco Sisignano2,3, Jessica Farger1

  • 1Institute of Functional and Clinical Anatomy, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.

Insights

Oxaliplatin-induced polyneuropathy (PN) causes dry eye disease (DED) through distinct mechanisms compared to diabetic polyneuropathy (DPN). Oxaliplatin-treated mice developed evaporative DED, unlike DPN mice which developed aqueous-deficient DED.

Area of Science:

  • Neuroscience
  • Ophthalmology
  • Pathology

Background:

  • Dry eye disease (DED) is frequently observed in patients with polyneuropathies (PNs).
  • The specific relationship between different types of PNs and DED remains unclear.
  • Investigating these connections can reveal novel therapeutic targets for DED.

Purpose of the Study:

  • To investigate the distinct mechanisms linking oxaliplatin-induced polyneuropathy (OPN) and diabetic polyneuropathy (DPN) to dry eye disease (DED).
  • To analyze morphological and molecular changes in ocular tissues and peripheral nerves in OPN.
  • To differentiate the types of DED caused by OPN versus DPN.

Main Methods:

  • Morphological analysis of sciatic nerve (SN), dorsal root ganglia (DRG), trigeminal ganglia (TG), and ocular tissues in oxaliplatin-treated mice.
  • Tear proteomics and gene expression analysis of ocular surface tissues.
  • Comparison of findings with previously studied DPN models.

Main Results:

  • Oxaliplatin-induced polyneuropathy (OPN) led to significant changes in six tear proteins and ocular tissue gene expression.
  • Morphological changes included decreased conjunctival goblet cells and altered Meibomian gland myofibroblasts.
  • OPN resulted in evaporative DED, contrasting with aqueous-deficient DED in DPN, with distinct trigeminal nerve findings.

Conclusions:

  • Oxaliplatin-induced polyneuropathy causes evaporative dry eye disease through mechanisms differing from diabetic polyneuropathy.
  • Peripheral nerve and ocular nerve damage patterns vary between OPN and DPN.
  • Understanding these differences is crucial for targeted DED treatment in specific polyneuropathy contexts.