An in vitro cell model to study microglia activation in diabetic retinopathy

Cell Biol Int. 2022 Jan;46(1):129-138. doi: 10.1002/cbin.11710. Epub 2021 Oct 21.

Abstract

Microglial activation has been studied extensively in diabetic retinopathy. We have previously detected activation and migration of microglia in 8-week-old diabetic rat retinas. It is widely acknowledged that microglia-mediated inflammation contributes to the progression of diabetic retinopathy. However, existing cell models do not explore the role of activated microglia in vitro. In this study, microglia were subject to various conditions mimicking diabetic retinopathy, including high glucose, glyoxal, and hypoxia. Under high glucose or glyoxal treatment, microglia demonstrated only partially functional changes, while under hypoxia, microglia became fully activated showing enlarged cell bodies, enhanced migration and phagocytosis as well as increased production of pro-inflammatory factors such as cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS). The data indicate that hypoxia-treated microglia is an optimal in vitro model for exploration of microglia activation in diabetic retinopathy.

Keywords: diabetic retinopathy; glyoxal; high glucose; hypoxia; microglial activation.

MeSH terms

  • Animals
  • Cell Hypoxia
  • Cell Line
  • Cell Movement* / drug effects
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology*
  • Disease Models, Animal
  • Glucose / toxicity
  • Glyoxal / toxicity
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phagocytosis* / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Retina / drug effects
  • Retina / metabolism
  • Retina / pathology*

Substances

  • IL1B protein, mouse
  • Inflammation Mediators
  • Interleukin-1beta
  • Glyoxal
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Glucose