Localization of endothelin-1 mRNA expression and immunoreactivity in the anterior segment of human eye: expression of ETA and ETB receptors.
OBJECTIVE
Endothelin-1 (ET-1), a potent vasoactive peptide, is an important regulator of intraocular pressure. Actually, there is evidence of a role for ET-1 in the pathogenesis of glaucoma. However, the expression pattern of ET-1 and its receptors, ETA and ETB, in the anterior segment of human eye are not known. In the current study, we have examined the expression and distribution of ET-1 as well as the expression profile of ETA and ETB genes in the iris, ciliary muscle, and ciliary processes of human eyes.


METHODS
Six normal human eyes with no history of eye diseases were fixed, embedded in paraffin and sectioned. Cellular localization of ET-1 was identified by in situ hybridization and immunohistochemistry. Iris, ciliary processes, and ciliary muscles were dissected from six normal human eyes and quantitative real time RT-PCR was used to quantify the expression of ETA and ETB.


RESULTS
In situ hybridization revealed the presence of ET-1 transcripts in the iris, nonpigmented epithelial ciliary cells, and ciliary muscle. Immunohistochemical studies showed that ET-1-like immunoreactivity appeared in the same regions where ET-1 mRNA was expressed as well as in trabecular cells, inner and outer endothelial cells lining Schlemm's canal, corneal epithelial, and limbus cells. Quantitative real time RT-PCR demonstrated that the expression of ETA and ETB receptors is greatest in the iris, followed by ciliary muscle and ciliary processes.


CONCLUSIONS
ET-1 and its receptors ETA and ETB are constitutively expressed in the anterior segment of human eye. These results indicate that ET-1 may play a physiological role in the regulation of intraocular pressure through its ETA and ETB receptors in human eye. In addition, ET-1 present in corneal epithelium and limbus may function in regulating cell proliferation and/or differentiation.
Fernández-Durango
Raquel
R
Unidad de Investigacion, Departamento de Medicina Interna III, Hospital Clinico San Carlos, Ciudad Universitaria, Madrid, Spain.
Rollín
Raquel
R
Mediero
Aránzazu
A
Roldán-Pallares
Manuela
M
García Feijo
Julián
J
García Sánchez
Julian
J
Fernández-Cruz
Arturo
A
Rípodas
Ainhoa
A
D000368:Aged; D000869:Anterior Eye Segment / Q000378:metabolism*; D002924:Ciliary Body / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007498:Iris / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin