Potential Protective Role of TRPM7 and Involvement of PKC/ERK Pathway in Blue Light–Induced Apoptosis in Retinal Pigment Epithelium Cells in Vitro

Abstract

Purpose: Blue light triggers apoptosis of retinal pigment epithelium (RPE) cells and causes retinal damage. The aim of this study was to elucidate the protective role of transient receptor potential melastatin 7 (TRPM7) in photodamaged RPE cells. Methods: RPE cells were isolated from Sprague-Dawley (SD) rats and exposed to varying intensities of blue light (500–5000 lux) in vitro. Cell proliferation and metabolic activity were respectively assessed by bromodeoxyuridine (BrdU) incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to analyze the TRPM7, protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and Bcl2-associated x/B-cell lymphoma 2 (Bax/Bcl-2) messenger RNA (mRNA) and protein expression levels. The cells were transfected with TRPM7 small interfering RNA (siRNA) or transduced with TRPM7-overexpressing lentiviruses and cultured with or without the pigment epithelium-derived factor (PEDF). Results: Blue light inhibited the proliferation and metabolic activity of RPE cells in an intensity-dependent manner when compared to nonirradiated controls ( P < 0.05). Compared to the control, photodamaged RPE cells showed decreased levels of TRPM7, PKC, ERK, and Bax, and an increase in Bcl-2 levels ( P < 0.01). Forced expression of TRPM7 partially rescued the proliferative capacity of RPE cells ( P < 0.01) and restored the levels of TRPM7, PKC, ERK, and Bax ( P < 0.01), whereas TRPM7 knockdown had the opposite effects ( P < 0.01). TRPM7 and PEDF synergistically alleviated the damaging effects of blue light. Conclusions: Blue light triggers apoptosis of RPE cells, and its deleterious effects can be partially attenuated by the synergistic action of TRPM7 and PEDF via the PKC/ERK signaling pathway.

Retinal Mechanical Sensation

“…Ischemia elicited a decrease in the ERG-recorded retinal responsiveness to light along with reactive gliosis and a significant increase in the expression of TRPM7 in Müller cells [248]. In another report [249], blue light triggered apoptosis of retinal pigment epithelial (RPE) cells, and its deleterious effects were partially attenuated by the synergistic action of TRPM7 and the pigment epithelium-derived factor (PEDF) via the PKC/ERK signaling pathway. The reverse transcription PCR analysis demonstrated the mRNA expression of TRPC1, TRPM7, TRPV1/2/4, and TRPP1, but not TRPC6 or TRPM4 in retinal vascular smooth muscle cells (VSMCs).…”

Deciphering the Effects of Different Types of Sunlight Radiation on Skin Function: A Review

“…Research on the toxic and genotoxic consequences of blue light has mostly focused on the therapeutic and ophthalmic risks. It was reported that blue light damages the retina, induces cell dysfunction and mortality in gingival and lens epithelial fibroblasts, and causes apoptosis in retinal pigment epithelium (RPE) cells [1,121].…”