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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.
Abstract:
Dry eye disease (DED) is often seen in patients with polyneuropathies (PNs), but the relationship between the different forms of PNs and DED is not known. In oxaliplatin (Ox-)-treated mice with PNs, morphological changes in the sciatic nerve (SN), dorsal root ganglia (DRG), trigeminal ganglia (TG), and the ocular tissues involved in tear formation were investigated. In addition, the tear proteomics and the gene expression of related proteins in the ocular surface tissues as well as inflammatory factors were analyzed. There were significant changes in six tear proteins compared to the controls, with respective changes in gene expression in the ocular tissues. Morphologically, there was a decrease in the number of conjunctival goblet cells and changes in the myofibroblasts surrounding the Meibomian glands. The lacrimal gland appeared normal. In the SN, there was a slight decrease in the number of mitochondria without signs of inflammation. In the DRG, 30-50% of the small- and medium-sized neuronal cells had swollen mitochondria. In contrast, the mitochondria of the TG were unremarkable. The changes in the tear film proteins and the ocular tissue morphology involved in tear formation in OPN differed significantly from those previously described in DPN mice, despite a similar mechanical hypersensitivity and similar morphological features of the DRG. In DPN, these changes led to aqueous-deficient dry eye disease, whereas in OPN, they resulted in evaporative DED. Furthermore, in contrast to DPN, the TG in OPN showed no morphological alterations, which indicates differences in the peripheral nerve changes and ocular nerve damage between the two conditions.
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.

