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Protective effects of CRTH2 suppression in dry age-related macular degeneration.
- Source :
-
Biochemical & Biophysical Research Communications . Oct2022, Vol. 624, p8-15. 8p. - Publication Year :
- 2022
-
Abstract
- 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 H 2 O 2 , CRTH2 mRNA expression in cells tended to increase. Flow cytometry revealed that the CRTH2 inhibitor could protect the RPE from apoptosis. After NaIO 3 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, NaIO 3 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. • Prostaglandin D 2 generated by retinal pigment epithelium (RPE) was increased upon H 2 O 2 stimulation. • CAY10471 protects RPE cells against H 2 O 2 -induced apoptosis. • Chemokine receptor expressed on type 2 helper T cells (CRTH2) deficiency reduced sodium iodate-induced retinal degeneration. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 624
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 158604862
- Full Text :
- https://doi.org/10.1016/j.bbrc.2022.07.003