Abstract
The retinal pigment epithelium (RPE) performs many functions that maintain photoreceptor health. Oxidative damage to the RPE is a critical component in the pathogenesis of eye diseases such as age-related macular degeneration (AMD). Ligands of the cluster of differentiation 36 (CD36) have previously preserved photoreceptor integrity in mouse models of AMD. The cytoprotective effect of the CD36 ligand MPE-001 on RPE cells has now been elucidated employing a model of oxidative stress. Sodium iodate (NaIO3) induced formation of reactive oxygen species and apoptosis in human RPE cells, which were decreased by MPE-001 without affecting antioxidant enzyme transcription. Immunoblotting and immunostaining assays showed a restorative effect of MPE-001 on the autophagic flux disrupted by NaIO3, which was associated with an increase in syntaxin 17-positive mature autophagosomes. The cytoprotective effect of MPE-001 was completely abolished by the autophagy inhibitors wortmannin and bafilomycin A1. In conclusion, we report for the first time an autophagy-dependent protection of RPE cells from oxidative stress by a CD36 ligand.
Highlights
The retinal pigment epithelium (RPE) is a monolayer of polarized epithelial cells located posterior to the neuroretina in close contact with photoreceptors
The role of oxidative stress in the pathogenesis of age-related macular degeneration (AMD) is supported by observations of an AMD-like phenotype in mice with a genetic deficiency in either superoxide dismutase 1 or 2 (Sod1 [4] or Sod2 [5]) or nuclear factor erythroid 2-like 2 (Nfe2l2)
We examined the potential of cluster of differentiation 36 (CD36) as a target to modulate oxidative stress in the RPE
Summary
The retinal pigment epithelium (RPE) is a monolayer of polarized epithelial cells located posterior to the neuroretina in close contact with photoreceptors. High metabolic activity combined with exposure to light and photochemical reactions in the oxygenated environment render the RPE prone to oxidative stress. Oxidative damage to the RPE can lead to dysfunction with cell loss, inflammation, and degeneration of photoreceptors, characteristics of age-related macular degeneration (AMD) [1]. AMD is a leading cause of visual impairment in the elderly population [2] and is categorized into wet (neovascular) and dry (atrophic, nonneovascular) forms with distinct pathophysiological features. Hallmarks of dry AMD include RPE abnormality with accumulation of a complex deposit of lipids and proteins called drusen and atrophy of the photoreceptor layer in the macular region of the retina [1]. The role of oxidative stress in the pathogenesis of AMD is supported by observations of an AMD-like phenotype in mice with a genetic deficiency in either superoxide dismutase 1 or 2 (Sod1 [4] or Sod2 [5]) or nuclear factor erythroid 2-like 2 (Nfe2l2)
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