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Hui Lin, Siva Pramodh Kambhampati, Chihchien Hsu, Kannan Rangaramanujam, Samuel C Yiu; Subconjunctival dendrimer-drug therapy for the treatment of dry eye in rabbits with induced autoimmune dacryoadenitis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4920. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the efficacy of a single subconjunctival injection of dendrimer- dexamethasone to treat dry eye in a rabbit model of induced autoimmune dacryoadenitis (AID).
AID was induced by injecting autologous peripheral blood lymphocytes activated in a mixed cell reaction with autologous acinar cells back into the animal’s lacrimal gland (LG). Diseased animals were treated with free dexamethasone (Free-Dex), dendrimer-dexamethasone (D-Dex), or saline via a single subconjunctival injection. The clinical evaluations, including Schirmer’s test, tear breakup time (TBUT), and fluorescein and rose bengal staining, were performed. Histopathology was evaluated by H&E staining and immunostaining. Levels of inflammatory cytokines and aquaporin proteins in the LGs were determined by real-time PCR.
Subconjunctivally administered dendrimers selectively localized in the inflamed LGs, and were taken up by the infiltrated cells. At two weeks post-treatment, the D-Dex group showed increased tear secretion and TBUT in comparison to diseased animals pre-treatment. No significant changes were observed in other treatment groups. On H&E staining, there was less inflammatory cell infiltration and fewer atrophic acini in D-Dex treated LGs, compared to those treated with saline or Free-Dex. Immunohistochemistry demonstrated that the intensity of CD-18 (+) and RTLA (+) was weaker in LGs in the D-Dex group than in the Free-Dex or saline-treated rabbits. Gene expression levels of IL-6, IL-8, and TNF-α were decreased in both the D-Dex and Free-Dex groups compared to the saline group, while the expression of aquaporin 4 was increased in the D-Dex group.
The dendrimer exhibits pathology-dependent biodistribution in the inflamed LGs. Subconjunctivally administered D-Dex suppressed LG inflammation, leading to partial recovery of LG function with clinical improvement in induced AID. Sjögren’s patients may benefit from this targeted nanomedicine approach.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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