Complete Dacryoadenectomy in Rabbits: A Novel Approach to Create Dry Eye Disease

Abstract

Purpose : We developed a novel method for complete removal of all rabbit lacrimal gland (LG) tissues. Our hypothesis is that complete dacryoadenectomy will create a chronic, more severe form of dry eye disease (DED) than possible with partial LG removal or Concanavalin A (ConA) injection and similar severity to LG denervation.

Methods : 8 New Zealand White rabbits underwent surgical removal of the Superior Lacrimal Gland (SLG), Palpebral Lacrimal Gland (PLG), and Inferior Lacrimal Gland (ILG). Dry eye status was assessed with Tear osmolarity (TOsm), Tear Break Up Time (TBUT), Schirmer’s Tear Test (STT), Rose Bengal Staining (RBS) and conjunctival impression cytology (CIC). Measures were taken at baseline and weeks 1,2,3,4 and 6 after surgery.

Results : Resected SLG, ILG, and PLG were examined histologically and shown to be consistent with LG tissues. (Fig 1A) Complete LG removal resulted in significant reductions of STT (18.2±4.7 / 7.6±4.1 mm), TBUT (60±0 / 7.6±14 sec), and a significant increases in TOsm (297±14.3 / 335±12) and RBS (0±0 / 6.6±4.5 modified NEI scale) (baseline/ week 6 data ; mean±SD; p<0.05 for all) All eyes had normal CIC at baseline (Fig 1B). All eyes developed loss of goblet cells and signs of moderate to high grade squamous metaplasia (Tseng scale) consistent with severe DED (Fig. 1C) STT reduction with complete dacryoadenectomy (58%) was greater than that described for partial surgical resections (approx 40%) or Concanavalin A induced DED (approx 30%). A slightly greater STT reduction was reported with denervation of the LG (approx 70%).

Conclusions : We describe a method of complete dacryoadenectomy in rabbits that creates a severe, chronic DED. Our work confirms the hypothesis that complete removal of the LG results in greater STT reductions than models created with partial resection of LG or injections of ConA. Tear production, even with complete resection, is not completely abolished. The model is reproducible, safe, and has stable DED parameters for at least 6 weeks. The method is a useful addition to the available models for studying DED and can shed light on compensatory sources of fluid production for the ocular surface in rabbits. Finally, given the very low ocular levels of carboxylesterase (CE) in rabbits this model allows the preclinical evaluation of novel therapeutic agents for DED that are metabolized by CE and not easily studied in murine models possessing high CE activity levels.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.