Protective effects of CRTH2 suppression in dry age-related macular degeneration
2022
Xie, Ruotian | Wang, Bei | Zuo, Shengkai | Du, Mei | Wang, Xiaohong | Yu, Ying | Yan, Hua
Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Oxidative stress-induced retinal pigment epithelium (RPE) cell apoptosis is a crucial pathogenic hallmark in AMD. Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a prostaglandin (PG) D2 receptor, has been implicated in various pathophysiological events, especially inflammation and stress-induced cell apoptosis. However, its specific role in AMD is not fully understood. Here we studied the effect of CRTH2 on AMD. Our results showed that when stimulated by H₂O₂, CRTH2 mRNA expression in cells tended to increase. Flow cytometry revealed that the CRTH2 inhibitor could protect the RPE from apoptosis. After NaIO₃ injection, a larger area of retinal degeneration was observed in wild-type mice than in CRTH2⁻/⁻ mice. Optical coherence tomography (OCT) and Hematoxylin and Eosin (H&E) staining of retinal sections showed that sodium iodate-induced loss of photoreceptor cells was reduced in CRTH2⁻/⁻ mice after treatment; TUNEL-positive cells were mostly found in the outer nuclear layer. In the control group, NaIO₃ stimulation increased the number of TUNEL-positive cells, whereas the percentage of TUNEL-positive cells was significantly lower in CRTH2⁻/⁻ mice. Similarly, the CRTH2 receptor inhibitor CAY10471 similarly inhibited sodium iodate-induced retinal damage. Our results suggest that targeting CRTH2 is a promising therapeutic strategy for the treatment of progressive retinal degeneration in AMD.
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