期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 624, 期 -, 页码 8-15出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.07.003
关键词
Age-related macular degeneration; Chemoattractant receptor-homologous; molecule expressed on T helper type 2 cells; Sodium iodate
资金
- National Natural Science Foundation of China [81900883]
- Beijing-Tianjin-Hebei Special Project [19JCZDJC64300, 20JCZXJC00180]
CRTH2 plays an important role in AMD. Inhibiting CRTH2 can protect RPE from apoptosis, reduce retinal degeneration area, and prevent loss of photoreceptor cells. This suggests that CRTH2 may be a promising therapeutic target for treating AMD.
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. (C) 2022 Elsevier Inc. All rights reserved.
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