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Dhruva Bhattacharya, Yuan Ning, Fangkun Zhao, Rongji Chen, Jinsong Zhang, Mingwu Wang; Conjunctival Aquaporins Are Involved in the Resolution of Ocular Phenotype in a Rabbit Dry Eye Model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):320.
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© ARVO (1962-2015); The Authors (2016-present)
Longitudinal study of a rabbit dry eye model (over 4-months) found a spontaneous resolution of the dry eye phenotype. Mechanisms of tear fluid compensation in the absence of lacrimal gland were explored.
A rabbit dry eye model was created by bilateral resection of lacrimal gland (LG), Hardarian gland (HG) and nictitating membrane (NM). Ocular surface of these rabbits (N=8) were characterized by clinical tests (Schirmer tests, fluoroscein test, and rose Bengal staining). In parallel, conjunctival impression cytology (CIC) was done before excision (BE) and every month after excision (AE) over 4-months. Conjunctival molecular biomarkers was studied to supplement the clinical tests, including inflammatory cytokine genes (interleukin 1β: IL-1β, tumor necrosis factor: TNF-α) and matrix metalloproteinase (MMP-9), using Reverse Transcription-Quantitative-Polymerase Chain Reaction (RT-qPCR). To assess involvement of conjunctiva in restoration of ocular fluid balance, the following genes were assessed by RT-qPCR of CIC: cystic fibrosis trans-membrane conductance regulator: CFTR, sodium potassium chloride co-transporters: NKCC1, sodium potassium ATPase: NKA; epithelial sodium channels: ENaCα and water transporters: Aquaporins (AQP4, AQP5).
Dry eye phenotype in this rabbit model was confirmed at 1-month AE by increased fluorescein (P < 0.0001), rose Bengal (P < 0.0001) staining, and elevated biomarker mRNAs (IL-1β, P =0.0027; TNF-α, P =0.0045; MMP-9, P =0.0295). However, from 1-month on, fluorescein, rose Bengal staining and biomarkers reduced over time to near baseline (BE) at 4-months. Improvement of dry eye phenotype led to increased Schirmers test scores at 2 and 3-months (P =0.0009) and reduced to baseline at 4-months AE. Conjunctival CFTR, NKA, NKCC1 and ENaCα did not show any up regulation over 4-months. AQP4 was up regulated in 2-months AE and declined to baseline at 4-months AE. AQP5 too was up regulated at 1-month AE and stayed up-regulated at 4-months AE.
In absence of LG, HG and NM a spontaneous resolution of dry eye phenotype was observed in our rabbit model. The conjunctival AQPs are possibly involved in a compensatory tear fluid balance at ocular surface. Similar role played by accessory lacrimal glands cannot be excluded.
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