Subconjunctival dendrimer-drug therapy for the treatment of dry eye in rabbits with induced autoimmune dacryoadenitis
| Autor: | Ying Liu, Samuel C Yiu, Chih Chien Hsu, Rangaramanujam M. Kannan, Hui Lin, Siva P. Kambhampati |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Pathology Biodistribution Dendrimers medicine.medical_treatment Aquaporins Article Dexamethasone 03 medical and health sciences chemistry.chemical_compound Dacryocystitis 0302 clinical medicine polycyclic compounds Medicine Animals Fluorescein Saline business.industry Dacryoadenitis medicine.disease Staining Ophthalmology Disease Models Animal 030104 developmental biology chemistry Delayed-Action Preparations 030221 ophthalmology & optometry Cytokines Histopathology Dry Eye Syndromes Rabbits Injections Intraocular business hormones hormone substitutes and hormone antagonists Immunostaining Biomarkers medicine.drug |
| Popis: | Purpose To investigate the efficacy of a single subconjunctival injection of dendrimer-dexamethasone conjugate in a rabbit model of induced autoimmune dacryoadenitis (AID). Methods Dendrimer biodistribution after subconjunctival injection in AID animals was evaluated using Cy5-labelled dendrimer (D-Cy5) and confocal microscopy. Diseased animals were treated with free dexamethasone (Free-Dex), dendrimer-dexamethasone (D-Dex), or saline via a single subconjunctival injection. The efficacy was evaluated using various clinical evaluations, such as Schirmer's test, tear breakup time (TBUT), and fluorescein and rose Bengal staining. 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. Results Subconjunctivally administered dendrimers selectively localized in the inflamed LGs, and were taken up by the infiltrating cells. At two weeks post single dose-treatment, the D-Dex group showed improved clinical evaluations. No significant changes were observed in other groups. H&E staining demonstrated less inflammatory cell infiltration and fewer atrophic acini in D-Dex group, 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 other treatment groups. Pro-inflammatory gene expression levels of MMP9, IL6, IL8, and TNFα were significantly decreased in the D-Dex group compared to the Free-Dex and saline group. Conclusions 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. Sjogren's patients may benefit from this targeted nanomedicine approach. |
| Databáze: | OpenAIRE |
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