atrial-natriuretic-factor and Glaucoma--Open-Angle

The aim of this study is to determine differences in the levels of NT-proANP in the plasma and aqueous humor of glaucoma and cataract patients and to evaluate whether any relationships are present.. The study group consisted of 58 patients with primary-open glaucoma (POAG) undergoing trabeculectomy surgery. The control group was comprised of 32 age-matched cataract patients. The concentration of the N-terminal fragment of the proatrial natriuretic peptide (NT-proANP, 1-98) in the aqueous humor and blood plasma samples was measured using an immunochemical method (ELISA).. The plasma NT-proANP concentration was significantly increased in patients with POAG compared to that in the control group (7.00 vs. 4.65 nmol/L, P = 0.0054). Similarly, the NT-proANP concentration in the aqueous humor was significantly higher in the POAG patients (0.47 vs. 0.09 nmol/L, P = 0.0112). However, there was no correlation between the NT-proANP values in the aqueous humor and the plasma of the POAG patients, as well as between the NT-proANP values in the aqueous humor and the intraocular pressure.. We identified an association between the levels of NT-proANP in the plasma and the aqueous humor with POAG. Our data support the idea of the involvement of NP system in the development of POAG and highlight ANP as a possible biomarker of glaucoma.

Topics: Aged; Aqueous Humor; Atrial Natriuretic Factor; Biomarkers; Cataract; Cataract Extraction; Enzyme-Linked Immunosorbent Assay; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Trabeculectomy

1. Familial primary open-angle glaucoma (POAG) is a heterogeneous disease of unknown aetiology and the elucidation of the underlying genetic mechanisms contributing to phenotypic expression will be essential if earlier diagnosis of at-risk individuals and more specific medical treatment can be achieved. In a significant percentage of patients with POAG, intraocular pressure increases in response to topical ocular glucocorticoids. 2. Atrial natriuretic peptide (ANP) assists in the regulation of intraocular pressure levels and binding of the glucocorticoid receptor dimer to the glucocorticoid-responsive element in intron 2 of the ANP gene has been shown to increase ANP mRNA levels in vitro. We amplified and examined this sequence in the ANP gene by PCR-SSCP analysis in 100 patients with familial POAG and in 60 normal control subjects. No base alterations in the amplified product were found. 3. Thus, the present study found no evidence for an alteration in the sequence of the glucocorticoid-responsive element of the ANP gene that could alter ANP gene transcription in patients with familial POAG. The mechanism responsible for the increase in intraocular pressure levels in response to glucocorticoids is most likely independent of the glucocorticoid-responsive element in the ANP gene.

Topics: Atrial Natriuretic Factor; Glaucoma, Open-Angle; Glucocorticoids; Humans; Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Regulatory Sequences, Nucleic Acid

Family history is a major risk factor in the development of primary open-angle glaucoma. The atrial natriuretic peptide system has been implicated in the underlying pathophysiology of the disease. This study looked for any alterations in the ANP gene and 5' proximal promoter regions of the ANP gene, in 53 patients from familial primary open-angle glaucoma families. The ANP gene was amplified by a long-PCR technique from peripheral blood DNA. Gross insertions or deletions in the gene were sought and allelic frequencies at two restriction fragment length polymorphism (RFLP) sites within the gene (Sca I, Hpa II) were compared with allelic frequencies obtained from 60 normal controls with no known family history of glaucoma or ocular hypertension. PCR-based single strand conformation polymorphism analysis was then used to search for possible point mutations in the 5' proximal promoter region of the ANP gene, which is known to contain regulatory elements which modify gene transcription. No gross alterations in the ANP gene or differences in allelic frequencies at the RFLP sites within the gene were observed. PCR-SSCP analysis of the 5' proximal promoter region of the gene revealed mutations in 10 patients in the -595 to -384bp region (19% of patients). Mutations in the 5' proximal promoter region of the ANP gene may contribute to altered ANP transcription in at least a proportion of patients with familial glaucoma.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Atrial Natriuretic Factor; Base Sequence; Deoxyribonucleases, Type II Site-Specific; DNA; DNA Primers; DNA-Cytosine Methylases; Female; Gene Frequency; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Molecular Sequence Data; Ocular Hypertension; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; Promoter Regions, Genetic; Reference Values; Risk Factors; Transcription, Genetic

The presence of receptors for atrial natriuretic factor (HANaP) on the ciliary body leads to the conclusion that HANaP may play a role in the regulation of intraocular pressure. In two groups of patients (each group consisted of ten patients) the injection of 100 mg HANaP was followed by a significant lowering of the intraocular pressure. This effect could be seen over a period of 4 h. The intraocular pressure was reduced by about 25% of the baseline pressure.

Topics: Atrial Natriuretic Factor; Cataract Extraction; Glaucoma, Open-Angle; Humans; Injections, Intravenous; Intraocular Pressure; Pilot Projects; Postoperative Complications