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Review
. 2021 Nov 14;22(22):12298.
doi: 10.3390/ijms222212298.

Molecular Mechanisms of Retinal Pigment Epithelium Dysfunction in Age-Related Macular Degeneration

Jongmin Kim  1 , Yeo Jin Lee  2   3 , Jae Yon Won  2   3
Affiliations
Review

Molecular Mechanisms of Retinal Pigment Epithelium Dysfunction in Age-Related Macular Degeneration

Jongmin Kim et al. Int J Mol Sci. .

Abstract

The retinal pigment epithelium (RPE), situated upon Bruch's membrane, plays multiple roles in the ocular system by interacting with photoreceptors and. Therefore, dysfunction of the RPE causes diseases related to vision loss, such as age-related macular degeneration (AMD). Despite AMD being a global cause of blindness, the pathogenesis remains unclear. Understanding the pathogenesis of AMD is the first step for its prevention and treatment. This review summarizes the common pathways of RPE dysfunction and their effect in AMD. Potential treatment strategies for AMD based on targeting the RPE have also been discussed.

Keywords: age-related macular degeneration; retinal pigment epithelium.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
Multimodal image of age-related macular degeneration (AMD). Color fundus photograph and swept source optical coherence tomography (SS-OCT) images show the feature of early, intermediated AMD, neovascular AMD and geographic atrophy (a,b). Non-neovascular AMD (dry AMD): small and intermediate soft drusen. (c) Neovacular AMD (wet AMD): submacular hemorrhage, subretinal fluid and pigment epithelial detachement. (d) Geographic atrophy: retinal pigment epithelial pigment and photoreceptor atrophy at fovea.
Figure 2
Figure 2
Overview of necrosis, apoptosis, and pyroptosis pathways involved in retinal pigment epithelium (RPE) cell death in age-related macular degeneration. In necrosis, the necrosome forms complex proteins that attach to the mitochondrial membrane, triggering cell death. Apoptosis can be activated through the intrinsic or extrinsic pathways, which eventually result in the activation of caspase 3 and then cell death. Pyroptosis can occur through caspase 1-dependent or independent pathways, which lead to the generation of an N-terminal fragment that induces cell death.
Figure 3
Figure 3
Overview of the mechanisms of photobiomodulation (PBM). PBM activates mitochondrial cytochrome oxidase C and increases mitochondrial respiration and nitric oxide dissociation. These processes elevate ATP, cAMP, reactive oxygen species, and intracellular calcium levels, promoting anti-inflammation, antioxidation, protein synthesis, anti-apoptosis, and cellular metabolism. The antioxidation effect of PBM increases RPE phagocytosis.
See this image and copyright information in PMC

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