Natriuretic peptide system in the human retina.
OBJECTIVE
The natriuretic peptide (NP) family includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Natriuretic peptides are known to inhibit vascular cell growth and regulate vessel tone. There is also much evidence to suggest they modulate vascular permeability and angiogenesis, as well as regulating aqueous humor production in the eye. All these data indicate that the natriuretic peptide system might be involved in the development of diabetic retinopathy and glaucoma. Given the expression pattern of natriuretic peptides (NPs) and their receptors, natriuretic peptide receptor A (NPRA), natriuretic peptide receptor B (NPRB) and natriuretic peptide receptor C (NPRC) in the human retina has not yet been established, the present study was designed to determine ANP, BNP and CNP gene expression and localize the mature peptides in this tissue. The expression pattern of the genes encoding the different NP receptor subtypes was also examined.


METHODS
Eyes (n=10) from human donors with no history of eye disease were fixed and processed for routine paraffin embedding. The cellular location of the NPs was established by immunohistochemistry. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of NP and NP receptor genes in neural retinas obtained from the contralateral eyes.


RESULTS
Immunohistochemistry revealed the presence of NPs in the neural retina and retinal pigment epithelium. Positive NP immunostaining was observed within the astrocytes and in their processes enveloping vessels. In the anterior portion of the optic nerve, NPs were intensely labeled in neural bundles. We were able to detect NP gene expression in the human retina. The levels of NP receptor-encoding transcripts detected indicated no significant differential expression of genes coding for the different receptor subtypes.


CONCLUSIONS
Our finding that NP receptor transcripts are expressed along with ANP, BNP, and CNP mRNA in the human retina provides evidence for a local system in this tissue. The expression of NPs in neural retinal, glial, and vascular elements of the normal adult retina suggests a role for these peptides in maintaining both the neural and vascular integrity of the mature retina.
Rollín
Raquel
R
Unidad de Investigación, Departamento de Medicina Interna III, Hospital Clínico San Carlos, Madrid, Spain.
Mediero
Aránzazu
A
Roldán-Pallarés
Manuela
M
Fernández-Cruz
Arturo
A
Fernández-Durango
Raquel
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000235:genetics* / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; C058930:brain natriuretic peptide receptor; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C