Affiliation:
1. Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea
2. Department of Internal Medicine, Yale University, New Haven, CT 06520, USA
Abstract
Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.
Funder
Korea Research Foundation
Reference70 articles.
1. Epidemiology of age-related macular degeneration (AMD): Associations with cardiovascular disease phenotypes and lipid factors;Pennington;Eye Vis.,2016
2. Shingavi, M. (2020). Quantification of wet Age Related Macular Degeneration in Optical Coherence Tomography Angiography images. INFOCOMP J. Comput. Sci., 19.
3. Progress of clinical therapies for dry age-related macular degeneration;Rubner;Int. J. Ophthalmol.,2022
4. The diagnosis and treatment of age-related macular degeneration;Stahl;Dtsch. Ärzteblatt Int.,2020
5. Emerging therapies and their delivery for treating age-related macular degeneration;Thomas;Br. J. Pharmacol.,2022