Novel rabbit model for particulate matter-induced allergic conjunctivitis

Abstract

Purpose : Particulate matter (PM) is a primary trigger for the development of acute and chronic ocular surface disease, including allergic conjunctivitis. The purpose of the present study was to develop a novel rabbit model for PM-induced allergic conjunctivitis to facilitate future targeted drug discovery and development.

Methods : Standardized Reference Material (SRM^® 2786) consisting of fine atmospheric particulate of < 4 µm diameter was obtained from the NIST. Male and female New Zealand White rabbits (1.5 -2 kg) were exposed to PM by topical instillation (5 mg/ml, TID, 35 µl) for a period of up to 10 days. Ophthalmic lifitegrast solution (5%, formulated as Xiidra®) was administered for a period of 10 days following discontinuation of PM instillations. Ophthalmic examinations were performed by a veterinary ophthalmologist in awake animals and scored using the SPOTS system. Schirmer Tear Test (STT)
was collected using sterile diagnostic test strips. Corneal fluorescein staining was performed under isoflurane anesthesia using fluorescein ophthalmic strips. Images were recorded with a Spectralis HRT system in fluorescein angiography mode. Images were scored using the Oxford scoring system (0 - 5 scale) and the NEI scoring system (0 - 4 scale per quadrant with a maximum score of 16).

Results : Exposure to PM for 7 days caused severe hyperemia; tear volumes showed a small but significant reduction (10 ± 1 mm vs. 7.7 ± 0.8 mm, n = 16 eyes, P < 0.05). PM treatment significantly increased median corneal fluorescein staining (+ 2 scores in Oxford grading; n = 15 - 16 eyes, P < 0.001 and + 9 scores in NEI grading; n = 15 - 16 eyes, P < 0.001). Changes to the tear film and cornea were detectable by anterior segment SD-OCT imaging. Discontinuation of PM treatment did not improve hyperemia or corneal fluorescein staining in untreated eyes after 10 days. In contrast, topical instillation of lifitegrast resolved hyperemia (n = 4 eyes, P < 0.05) and significantly reduced corneal fluorescein staining (n = 4, P < 0.001). Lifitegrast treatments had no effect on STT.

Conclusions : PM exposure induces ocular surface disease that is responsive to immunosuppressant therapy. To our knowledge this is the first report of a large animal model to study PM-induced ocular surface disease. Our new rabbit model offers a standardized experimental paradigm for the in vivo testing of novel therapeutic approaches targeting PM-induced allergic conjunctivitis.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.