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Ying Liu, Hui Lin, Siva Pramodh Kambhampati, Kannan Rangaramanujam, Samuel C Yiu; Dendrimer-dexamethasone therapy improved lacrimal gland function in an induced autoimmune dacryoadenitis rabbit model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4390.
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© ARVO (1962-2015); The Authors (2016-present)
Sjögren syndrome (SS), characterized by focal lymphocytic infiltration and severe dysfunction of the exocrine organs, is one of the most common causes of dry eye. Ocular surface and lacrimal gland (LG) inflammation has been identified to play a vital role in the pathogenesis of dry eye. Anti-inflammatory drugs are widely used for the treatment of the inflammation with topical corticosteroid drops. Dendrimers are known to enhance anti-inflammatory efficacy in several diseases through targeted delivery. We aim to evaluate single subconjunctival injection of dendrimer-dexamethasone conjugate in the treatment of dry eye using a rabbit model of induced autoimmune dacryoadenitis (AID).
AID was induced by injecting autologous peripheral blood lymphocytes, which had been activated in a mixed cell reaction with acinar cells isolated from one inferior LG, back into the donor animal’s remaining inferior LG. Three groups of animals with established disease were treated with free dexamethasone (F-Dex), dendrimer-dexamethasone (D-Dex) or PBS via single subconjunctival injection. The clinical evaluations include Schirmer’s test, tear breakup time (BUT), fluorescein staining and rose Bengal staining. Histopathology was evaluated by H&E staining and immunostaining. The levels of inflammatory cytokines and aquaporin proteins in the LGs were determined by real-time PCR.
Only D-Dex treatment resulted in an increased tear secretion and BUT at 2 weeks. The score of Rose Bengal staining was significantly decreased in D-Dex group. But no significant change in fluorescein staining scores was observed among treatment groups. The H&E staining showed less inflammatory infiltration in D-Dex treated rabbits LG compared to PBS or F-Dex group. CD18 +, Iba+ and RTLA + staining was less in LGs of D-Dex and F-Dex treated rabbits than PBS group, while D-Dex group showed less staining than F-Dex group. D-Dex group showed more Aquaporin 5/4 immunostaining and higher AQP5 mRNA level than other treatment groups. The expression levels of matrix metalloproteinase-9, IL-6 and TNF-α were decreased in D-Dex group compared to PBS group.
Dendrimer mediated dexamethasone delivery via single subconjunctival injection results in the inhibition of inflammation and partial recovery of LG function in the induced AID model, which may contribute to the clinical improvements of SS patient.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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