Abstract
Nonexudative age-related macular degeneration (dry AMD) is characterized
by the accumulation of scattered drusen and progressive atrophy of
retinal pigment epithelial (RPE) cells, which leads to the degeneration
of photoreceptor cells and a decrease in central vision. MiR-21-5p plays
an important role in a variety of ophthalmological diseases, such as
diabetic retinopathy, glaucoma, pterygium, and laser-induced choroidal
neovascularization. Therefore, we speculate that miR-21-5p may be
involved in the regulation of RPE cell damage in AMD. Rats with
NaIO3-induced dry AMD received an intravitreal injection of miR-21-5p
agomir or antagomir. Optical coherence tomography (OCT), fundus,
histopathological studies and biochemical markers were assessed. We
observed high expression of miR-21-5p in NaIO3-treated rats.
Intravitreal injection of the miR-21-5p agomir significantly accelerated
NaIO3-induced RPE damage. This response was ameliorated by the
pretreatment of dry AMD model rats with the miR-21-5p antagomir.
Moreover, miR-21-5p regulated CoCl2-induced RPE cell necroptosis in
vitro, as shown by flow cytometry and immunostaining for receptor
interacting protein kinase 3 (RIP3) and HMGB1. Specifically, miR-21-5p
bound to the Pellino1 (Peli1) 3’ UTR to silence its expression. Peli1
overexpression effectively prevented CoCl2-induced RPE cell necroptosis.
These findings show the potential for miRNA-based therapy in the
treatment of dry AMD.