Targeted Microglial Attenuation through Dendrimer–Drug Conjugates Improves Glaucoma Neuroprotection
العنوان: | Targeted Microglial Attenuation through Dendrimer–Drug Conjugates Improves Glaucoma Neuroprotection |
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المؤلفون: | Ian Pitha, Siva Kambhampati, Anjali Sharma, Rishi Sharma, Liam McCrea, Ann Mozzer, Rangaramanujam M. Kannan |
المصدر: | Biomacromolecules |
بيانات النشر: | American Chemical Society (ACS), 2023. |
سنة النشر: | 2023 |
مصطلحات موضوعية: | Biomaterials, Polymers and Plastics, Materials Chemistry, Bioengineering, Article |
الوصف: | Retinal microglial/macrophage activation and optic nerve (ON) microglial/macrophage activation are glaucoma biomarkers and potential therapeutic targets for this blinding disease. We report targeting of activated microglia by PAMAM dendrimers in a rat glaucoma model and neuroprotection by N-acetylcysteine-conjugated dendrimer (D-NAC) conjugates in a post-injury rescue experiment. Intravitreally delivered fluorescently labeled dendrimer (D-Cy5) conjugates targeted and were retained in Iba-1-positive cells (90% at 7 days and 55% after 28 days) in the retina following intraocular pressure (IOP) elevation, while systemically delivered D-Cy5 targeted ON cells. A single intravitreal D-NAC dose given 1 week after IOP elevation significantly reduced transcription of pro-inflammatory (IL-6, MCP-1, IL-1β) and A1 astrocyte (Serping1, Fkbp5, Amigo2) markers and increased survival of retinal ganglion cells (39 ± 12%) versus BSS- (20 ± 15%, p = 0.02) and free NAC-treated (26 ± 14%, p = 0.15) eyes. These results highlight the potential of dendrimer-targeted microglia and macrophages for early glaucoma detection and as a neuroprotective therapeutic target. |
تدمد: | 1526-4602 1525-7797 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::244e7d4459b73667032be102a3090857 https://doi.org/10.1021/acs.biomac.2c01381 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....244e7d4459b73667032be102a3090857 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15264602 15257797 |
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