Abstract
Purpose :
To investigate the effectivity of topically administered everolimus-loaded methoxy-poly-ethylene-glycol hexyl substituted poly-lactic acid (mPEGhexPLA) based micellar nanocarriers for the treatment of EAU.
Methods :
EAU was induced in female B10.RIII mice (age 8 weeks) by immunization with human interphotoreceptor-retinoid-binding protein peptide 161-180 in complete Freunds adjuvant. Mice were treated five times per day starting on day 12 post immunization (p.i.) with 10µl of 0.5% everolimus-loaded mPEGhex-PLA micelles on the right eye (n=12) or PBS (n=12) as a control. Eyes, sera, cervical lymph nodes (LN) and spleens were collected on day 21 p.i.. The EAU-score was determined by histology. Antigen (Ag) or mitogen induced proliferation, cytokine secretion and frequency of FoxP3+ T-cells of isolated lymphocytes, and Ag-specific serum antibodies were determined via ELISA or flow-cytometry.
Results :
Compared to PBS treated mice, unilateral topical everolimus treatment led to reduced EAU incidence (p<0.05) and severity (p<0.05) in both eyes. The treatment also resulted in reduced Ag-specific serum antibodies (p<0.05), mitogen-induced proliferation (p<0.05), and reduced IL-2-, IL-17-, and IFN-γ -secretion in the cells from the right cervical LN (p<0.05). Under everolimus treatment, the IL-10 secretion (p<0.05) and Treg frequency in cervical LN was enhanced compared to the PBS group. The cytokine secretion, proliferative response, and frequency of CD4+CD25+FoxP3+ regulatory splenocytes were not significantly altered.
Conclusions :
Unilateral topical everolimus-loaded micelles improved EAU in both eyes. The effect is related to regional and also systemic immunomodulatory effects, as some systemic humoral and cellular immune responses are influenced.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.