| First Author | Galan A | Year | 2017 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 58 |
| Issue | 7 | Pages | 2852-2862 |
| PubMed ID | 28570737 | Mgi Jnum | J:257570 |
| Mgi Id | MGI:6112389 | Doi | 10.1167/iovs.16-20988 |
| Citation | Galan A, et al. (2017) Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy. Invest Ophthalmol Vis Sci 58(7):2852-2862 |
| abstractText | 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 mug subconjunctival (SCJ) depot to the reported effective 5 mug 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. |
