Inflammation, necrosis, and the kinase RIP3 are key mediators of AAG-dependent alkylation-induced retinal degeneration.

ABSTRACT: DNA-alkylating agents are commonly used to kill cancer cells, but the base excision repair (BER) pathway they trigger can also produce toxic intermediates that cause tissue damage, such as retinal degeneration (RD). Apoptosis, a process of programmed cell death, is assumed to be the main mechanism of this alkylation-induced photoreceptor (PR) cell death in RD. Here, we studied the involvement of necroptosis (another programmed cell death process) and inflammation in alkylation-induced RD. Male mice exposed to a methylating agent exhibited a reduced number of PR cell rows, active gliosis, and cytokine induction and macrophage infiltration in the retina. Dying PRs exhibited a necrotic morphology, increased 8-hydroxyguanosine abundance (an oxidative damage marker), and overexpression of the n

SUBMITTER: Allocca M 

PROVIDER: S-EPMC7150588 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature