RT Journal Article
T1 Involvement of carbonic anhydrases in the ocular hypotensive effect of melatonin analogue 5‐MCA‐NAT
A1 Crooke Álvarez, Almudena
A1 Huete Toral, Fernando
A1 Martínez Águila, Alejandro
A1 Martín Gil, Alba
A1 Pintor Just, Jesús Jerónimo
AB We have previously demonstrated that melatonin and its analogue, 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT), reduce intraocular pressure (IOP) in New Zealand rabbits. More recently, we have shown that 5-MCA-NAT can also regulate ciliary adrenoceptor gene expression. Like adrenoceptors, carbonic anhydrase (CA) enzymes are involved in aqueous humour secretion by the ocular ciliary epithelium. Moreover, CA enzymes have been reported to be regulated by melatonin. Hence, the aim of this study was to investigate whether the hypotensive effect of 5-MCA-NAT is also because of a regulation of CA genes and enzymes. Time course of 5-MCA-NAT effect on rabbit IOP was followed for 7 hr every day for up to 144 hr (6 days). 5-MCA-NAT reduced IOP, maximally by 51.30 ± 2.41% (at 3 hr), and the hypotensive effect was maintained for up to 96 hr with a single application. IOP studies with 5-MCA-NAT plus Trusopt® and immunohistochemical analysis confirmed that CA are molecular targets of 5-MCA-NAT. In addition, real-time quantitative PCR (qPCR) and immunocytochemical assays were performed to determine changes in CA2 (CAII) and CA12 (CAXII) expression in cultured rabbit nonpigmented ciliary epithelial cells (NPE) treated with 5-MCA-NAT. NPE cells showed a prominent decrease in both CA, at the mRNA and protein levels. These data confirm that the long-term hypotensive effect of 5-MCA-NAT is also due, to a down-regulation of CA2 (CAII) and CA12 (CAXII) expression.
PB Wiley
SN 0742-3098
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/101328
UL https://hdl.handle.net/20.500.14352/101328
LA eng
NO Crooke A, Huete-Toral F, Martínez-Águila A, Martín-Gil A, Pintor J. Involvement of carbonic anhydrases in the ocular hypotensive effect of melatonin analogue 5-MCA-NAT. J Pineal Res. 2012;52(3):265-270. doi:10.1111/j.1600-079X.2011.00938.x
NO Ministerio de Ciencia e Innovación (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 7 abr 2025