Abstract
Background: Uveitis is an infrequent disease which constitutes a major cause of ocular morbidity. Correct management is essential, being corticosteroids its cornerstone. In case of contraindication to corticosteroids or treatment failure, the use of topical tacrolimus (TAC) could be an alternative which has already demonstrated safety and effectiveness in other ocular pathologies. However, TAC eye drops are not marketed, thus their elaboration must be carried out in Hospital Pharmacy Departments (HPDs). Methods: 32 Sprague-Dawley rats were divided into 4 groups of 8 rats each: (a) untreated healthy rats (Healthy); (b) untreated Endotoxin-Induced Uveitis model-rats (EIU); (c) EIU-rats treated with standard treatment of dexamethasone ophthalmic drops (DXM) and (d) EIU-rats treated with TAC-hydroxypropyl-β-cyclodextrin eye drops previously developed by our group (TAC-HPβCD). The mRNA expression levels of IL-6, IL-8, MIP-1α and TNF-α, quantitative analysis of leucocytes in aqueous humor and histological evaluation were performed. Results: TAC-HPβCD eye drops demonstrated to reduce ocular inflammation, expression of IL-6, TNF-α, MIP-1α and leukocyte infiltration in aqueous humor. Conclusions: TAC-HPβCD eye drops showed beneficial effect in EIU model in rats, positioning as an alternative for uveitis treatment in case of corticosteroids resistance or intolerance.
Highlights
Uveitis constitutes a heterogeneous group of intraocular inflammatory diseases which is defined as inflammation of the uveal tract that can secondarily affect adjacent structures, such as the retina or the optical nerve [1,2]
Tacrolimus powder was acquired from Guinama® S.L.U. (La Pobla de Vallbona, Spain), 2-hydroxypropyl-β-cyclodextrin Kleptose® HPB (HPCD; MW = 1399 Da, substitution degree = 0.65 molar ratio) was provided from Roquette Laisa S.A.® (Valencia, Spain), Liquifilm® was purchased from Allergan® Pharmaceuticals Ireland (Mayo, Ireland), Maxidex® (1 mg/mL, eye drops) was purchased from Alcon Cusí, S.A.® (Barcelona, Spain) and Lipopolysaccharide endotoxin (LPS; Escherichia coli.) was obtained from Sigma-Aldrich (San Louis, MO, USA)
The mRNA presence of the pro-inflammatory cytokines (IL-6, IL-8, MIP-1α, and TNF-α) in the eye tissues was assessed by real time-PCR in order to evaluate the effect of TAC-HPβCD on factors involved in the inflammatory process
Summary
Uveitis constitutes a heterogeneous group of intraocular inflammatory diseases which is defined as inflammation of the uveal tract that can secondarily affect adjacent structures, such as the retina or the optical nerve [1,2]. From the pathophysiological point of view, the immune system plays a fundamental role in the development of uveitis, whether or not it is secondary to infectious processes [7] In this sense, the origin of inflammation can be attributed to an endogenous mechanism, either as part of autoimmune systemic diseases or as an isolated ocular condition [8]. Concerning the etiology of non-infectious uveitis, in recent years there have been significant advances in the understanding of their pathogenic mechanisms, pointing to the interaction between environmental factors and a complex genetic background, triggering a deregulated immune response able to overcome the ocular immune privilege [9,10] In this regard, different proinflammatory molecules are increased depending on the specific origin of the disease [11,12]. Conclusions: TAC-HPβCD eye drops showed beneficial effect in EIU model in rats, positioning as an alternative for uveitis treatment in case of corticosteroids resistance or intolerance
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