Purchase this article with an account.
Jana Dietrich, Mathias Roth, Gerd Geerling, Sonja Mertsch, Stefan Schrader; Evaluation of the regenerative potential of murine lacrimal gland tissue in two different models of lacrimal gland impairment. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4374.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Severe dry eye syndrome (DES) is commonly caused by a loss of functional lacrimal gland tissue (LG). Regeneration of LG would be a promising approach to treat DES, but underlying mechanisms are mainly unclear. Therefore, this study aims to evaluate LG regeneration in two mouse models and determine the most suitable model to study underlying mechanisms.
Male C57BL/6J mice (8-10 weeks) were used to induce damage in the right extraorbital LG by a single interleukin (IL) 1α (1µg/2µl) injection or ligation of the secretory duct for 7 days. Fluorescein staining (FL) of the eye, immunohistological scoring of inflammatory cells and histopathological evaluation of acinar structures and inflammation in H&E staining (n=6) were performed on day 1, 2, 3, 5, 7 after IL1α injection and day 3, 7, 14, 21, 28 after duct ligation. Untreated, saline injected or sham operated mice were used as controls (n=4).
FL was significantly increased in all groups for up to 3 days. Only in duct ligation FL was still significantly increased at day 7 and 14 (score 3±0.9) and returned to baseline at day 28 (score 1.7±0.5).After IL1α injection severe inflammation (2.7±0.5, p=0.003) was observed at day 1 which returned to baseline (0.8±0.8) at day 5. After duct ligation a severe inflammation (3.0, p<0.0001) was found up to day 14, followed by a decline to a moderate state (2.0, p=0.0012). In both models CD68 positive macrophages and to a smaller extent CD3 positive T cells, but no CD138 positive B cells infiltrated the LG.After IL1α injection 6/6 LG showed areas of partial destruction at day 1-2 with an almost complete reappearance of acinar structures at day 7. After duct ligation 6/6 LG had areas of severe destruction at day 3 which increased until day 7. Removal of ligation leads to a partial reappearance of acinar structures in only 2/6 LG at day 14 which increased until day 28.
Both models induce LG damage followed by a spontaneous regeneration of acinar structures. IL1α injection caused a prompt and severe inflammation with a transient period of tissue damage, imitating an acute inflammatory process. Duct ligation caused a more severe tissue damage followed by a prolonged period of regeneration, mimicking LG insufficiency. Further studies are needed to examine underlying mechanisms and the required extent of remaining functional tissue to successful regenerate LG.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only