Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration

Abstract

Retinal pigment epithelial (RPE) cells are an essential part of the human eye because they not only mediate and control the transfer of fluids and solutes but also protect the retina against photooxidative damage and renew photoreceptor cells through phagocytosis. However, their function necessitates cumulative exposure to the sun resulting in UV damage, which may lead to the development of age-related macular degeneration (AMD). Several studies have shown that UVB induces direct DNA damage and oxidative stress in RPE cells by increasing ROS and dysregulating endogenous antioxidants. Activation of different signaling pathways connected to inflammation, cell cycle arrest, and intrinsic apoptosis was reported as well. Besides that, essential functions like phagocytosis, osmoregulation, and water permeability of RPE cells were also affected. Although the melanin within RPE cells can act as a photoprotectant, this photoprotection decreases with age. Nevertheless, the changes in lens epithelium-derived growth factor (LEDGF) and autophagic activity or application of bioactive compounds from natural products can reverse the detrimental effect of UVB. Additionally, in vivo studies on the whole retina demonstrated that UVB irradiation induces gene and protein level dysregulation, indicating cellular stress and aberrations in the chromosome level. Morphological changes like retinal depigmentation and drusen formation were noted as well which is similar to the etiology of AMD, suggesting the connection of UVB damage with AMD. Therefore, future studies, which include mechanism studies via in vitro or in vivo and other potential bioactive compounds, should be pursued for a better understanding of the involvement of UVB in AMD.

Preventive Effects against Retinal Degeneration by Centella asiatica Extract (CA-HE50) and Asiaticoside through Apoptosis Suppression by the Nrf2/HO-1 Signaling Pathway

“…A2E, a metabolic by-product of RPE cells, induces dysfunction and apoptosis by accumulating and oxidizing in cells [ 21 , 22 ]. Therefore, we induced A2E oxidation by blue light (430 nm) in ARPE-19 cells and examined the antioxidant effect and cytoprotective effects of CA-HE50 and asiaticoside.…”

Culture surface protein coatings affect the barrier properties and calcium signalling of hESC-RPE

“…The hESC-RPE cells on LN were also more pigmented than on other coatings. The melanin pigment is an important factor in the RPE cells, minimizing light scatter and protecting the cells from cytotoxicity caused by light and inflammation 45 . In general, pigmentation has been considered as a differentiation marker for hPSC-RPE.…”

The Aging Stress Response and Its Implication for AMD Pathogenesis

“…High levels of damage in nDNA may induce cellular senescence, apoptosis or necrosis, while cells with a high level of mtDNA may survive as highly or persistently damaged mtDNA can be degraded [ 140 , 141 ]. However, the presence of multiple copies of damaged mtDNA may impact cellular functions and contribute to diseases [ 142 ]. As stated previously, ATM plays an important role in the aging stress response as it is a crucial DDR protein.…”