Engineered knockout of TRPA1 inhibits laser-induced choroidal neovascularization along with associated TGFb1 expression and neutrophil infiltration

• Published in: Laboratory investigation p. 100232
• Main Authors: Usui, Yuta, Iwanishi, Hiroki, Sumioka, Takayoshi, Ichikawa, Kana, Miyajima, Masayasu, Usui-Kusumoto, Keiko, Reinach, Peter Sol, Okada, Yuka, Saika, Shizuya
• Format: Journal Article
• Language: English
• Published: United States 09.08.2023
• Subjects: gene knockout; mouse; transient receptor potential ankyrin 1; Choroidal neovascularization; transforming growth factor β1; neutrophil; bone marrow transplantation

We examined the effects of gene ablation and chemical inhibition of transient receptor potential ankyrin 1 (TRPA1) on the growth of experimental argon laser-induced choroidal neovascularization (CNV) in mice. CNV was induced in the eyes of 6 - 8-week-old mice by argon laser irradiation and observed expression. This reaction was compared between TRPA1-null (KO) mice and wild-type (WT) mice. Gene expression analysis was performed in laser-injured tissues on day 1 and 3. CNV growth was evaluated on day 14. Finally, reciprocal bone marrow transplantation was performed between each genotype of mice to identify the responsible components of either recipient tissue or bone marrow-derived inflammatory cells. Results showed that laser irradiation successfully induced CNV growth at the site of laser injury. The size of induced CNV was significantly smaller in KO mice as compared with WT mice at day 14, as examined by angiography with fluorescein isothiocyanate-dextran. Invasion of neutrophils, but not macrophages, was suppressed in association with suppression of expression of transforming growth factor β1 in laser-irradiated KO tissues. Bone marrow transplantation indicated that the genotype of the recipient mouse, but not of inflammatory cells, is attributable to the KO phenotype. Systemic administration of a TRPA1 antagonist also downsized the CNV in a WT mouse. In conclusion, TRPA1 signal in local tissue cells is involved in the growth of laser-induced CNV. The phenotype was not attributable to both vascular endothelial cells and inflammatory cells. Blocking TRPA1 signal could be a potential treatment strategy for CNV-related ocular diseases. (244 words).