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Jessica Welss, Nichapa Phunchago, Marco Sisignano, Natarajan Perumal, Franz Grus, Jessica Feldt, Elke Lütjen-Drecoll, Friedrich P Paulsen; Changes in tears and ocular structures involved in tear film formation in chemotherapy-induced polyneuropathy in mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):265.
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© ARVO (1962-2015); The Authors (2016-present)
Polyneuropathy (PN) patients frequently show typical symptoms of dry eye disease (DED). However, the impact of neuronal degeneration processes to DED remains unclear. In this study, we used a chemotherapy-induced PN mouse model to investigate the effect on tear film and ocular structures involved in tear film formation.
C57BL/6 mice were treated once with 3mg/kg Oxaliplatin (Ox) (n=8) or Saline respectively. In 8 animals/group Schirmers test was performed at day 0 and day 10. Tears were collected at day 8, 9 and 10 by capillary tubes. Tear proteome changes were characterized in 3 animals/group by label-free quantitative mass spectrometry (MS)-based proteomics strategy. The MS spectra were analyzed by utilizing MaxQuant computational platform followed by functional annotation and pathway analyses. The eyes including eyelids and exorbital lacrimal glands (LG) of 6 animals/group were embedded in paraffin or EPON for morphological evaluation. To obtain a map of distribution of goblet cells in mice, 10μm serial sections of the whole eyeball and lids of 3 control mice were cut along the sagittal axis from nasal to temporal (228 sections/eye) and stained with Periodic Acid Schiff stain (PAS). The number of goblet cells in the conjunctival fornix of all serial sections was counted and compared with data of 3 treated mice obtained accordingly.
In normal mice the distribution of goblet cells differs markedly from that seen in humans. Most cells are found in the temporal quadrant. In PN mice, the number of goblet cells significantly decreased in the temporal region compared to the control group (P<0.01), while the middle and nasal area of the conjunctiva showed no significant differences. Small changes were seen in the central corneal epithelium, whereas LG gross morphology was not affected by Ox treatment. The tear volume was normal, but seven proteins (ATP13A2, RHOX4B, LPO, LTF, 1600014C10RIK, KRT1 and BOD1L1) were found to be significantly (P<0.05) differentially expressed.
Our preliminary data show, that even a single Ox treatment alters the number of goblet cells as well as specific proteins in the tears. It is currently unclear whether Ox affects the goblet cells or tear film directly or indirectly through intervention in neuronal processes.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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