Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy.
Invest Ophthalmol Vis Sci
; 58(7): 2852-2862, 2017 06 01.
Article
em En
| MEDLINE
| ID: mdl-28570737
ABSTRACT
Purpose:
The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections.Methods:
We compared the pharmacokinetics of a single 40 µg subconjunctival (SCJ) depot to the reported effective 5 µg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death.Results:
The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure.Conclusions:
Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Triancinolona Acetonida
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Receptores de Fator de Crescimento Neural
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Diabetes Mellitus Experimental
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Retinopatia Diabética
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article