Adrenomedullin and Leptin Levels in Diabetic Retinopathy and Retinal Diseases

Purpose: Proliferative and vascular retinal diseases are important cause of irreversible blindness. Consistent features of these diseases are endothelial dysfunction and angiogenesis. Adrenomedullin (ADM) is a multifunctional vasorelaxant peptide. Leptin is a recently discovered metabolic peptide that regulates energy metabolism in human. In the present study, we aimed to investigate the possible roles of adrenomedullin and leptin in the pathophysiology of diabetic and proliferative diseases. Methods: Ten patients with proliferative diabetic retinopathy (57.1 years, 5 female and 5 male) and 8 patients (51 years, 5 female and 3 male) with other retinal diseases including macular hole and epiretinal membrane were included in this study. All the patients had undergone pars plana vitrectomy for complications of the diseases. Vitreous samples were collected by vitreous tap during the vitrectomy. Adrenomedullin analysis was made by using reverse-phase high-performance liquid chromatography (HPLC). Leptin was measured by enzyme-linked immunosorbent assay (ELISA). Body mass index (BMI) [weight (kg)/height (m2)] was calculated for each group. The Mann-Whitney U test was used for statistics. Results: The age, gender ratio and BMI were not substantially different between the two groups. The mean vitreous adrenomedullin levels (63.9 ± 7.1 pmol/l) were significantly higher (p < 0.05) in group I than in group II (34.25 ± 3.0 pmol/l). Leptin levels in vitreous (4.54 ±1.6 ng/ml) were also significantly higher (p < 0.05) in patients with diabetic retinopathy than in those without diabetes (1.83 ± 0.5 ng/ml). Conclusion: Increased adrenomedullin and leptin levels in vitreous humor might be a possible newly associated factor in the course of vascular and proliferative retinal diseases.

[1]  K. Takahashi,et al.  Elevated adrenomedullin in the vitreous of patients with proliferative vitreoretinopathy. , 1999, American journal of ophthalmology.

[2]  T. Sakamoto,et al.  Elevated Adrenomedullin in the Vitreous of Patients with Diabetic Retinopathy , 2003, Ophthalmologica.

[3]  Y. Okano,et al.  Ocular effects of adrenomedullin. , 1999, Experimental eye research.

[4]  K. Kangawa,et al.  Distribution and characterization of immunoreactive rat adrenomedullin in tissue and plasma , 1994, FEBS letters.

[5]  W. Alvord,et al.  Interleukin 1 alpha increases serum leptin concentrations in humans. , 1997, The Journal of clinical endocrinology and metabolism.

[6]  E. Hazneci,et al.  Increased Plasma Adrenomedullin Levels in Patients with Behçet’s Disease , 2000, Dermatology.

[7]  L. Montuenga,et al.  Expression of adrenomedullin and its receptor during embryogenesis suggests autocrine or paracrine modes of action. , 1997, Endocrinology.

[8]  K. Takahashi,et al.  Adrenomedullin in cultured human retinal pigment epithelial cells. , 2000, Investigative ophthalmology & visual science.

[9]  K. Takahashi,et al.  Induction of adrenomedullin by hypoxia in cultured retinal pigment epithelial cells. , 2001, Investigative ophthalmology & visual science.

[10]  C. Pesquera,et al.  Plasma Adrenomedullin Levels in Type 1 Diabetes: Relationship with clinical parameters , 1998, Diabetes Care.

[11]  A. Simopoulos.  Obesity and body weight standards. , 1986, Annual review of public health.

[12]  B. Otlu,et al.  Serum leptin concentration is increased in patients with Behçet's syndrome and is correlated with disease activity , 2002, The British journal of dermatology.

[13]  C. Wahlestedt,et al.  Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Gariano,et al.  Elevation of vitreous leptin in diabetic retinopathy and retinal detachment. , 2000, Investigative ophthalmology & visual science.

[15]  N. Minamino,et al.  Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. , 1995, Biochemical and biophysical research communications.

[16]  K. Kangawa,et al.  Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. , 1993, Biochemical and biophysical research communications.

[17]  F. Casanueva,et al.  Synthesis of leptin in human placenta. , 1997, Endocrinology.

[18]  M. Asakawa,et al.  The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells , 1999, FEBS letters.

[19]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[20]  A. Bado,et al.  The stomach is a source of leptin , 1998, Nature.

[21]  Z. Tulassay,et al.  Adrenomedullin and diabetes mellitus , 2001, Diabetes/metabolism research and reviews.

[22]  K. Miyamoto,et al.  Endothelial cells actively synthesize and secrete adrenomedullin. , 1994, Biochemical and biophysical research communications.

[23]  C. Pournaras,et al.  RETINAL OXYGEN DISTRIBUTION: Its Role in the Physiopathology of Vasoproliferative Microangiopathies , 1995, Retina.

[24]  W. Alvord,et al.  Interleukin 1α Increases Serum Leptin Concentrations in Humans , 1997 .

[25]  W. Stremmel,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Tumor Necrosis Factor Increases Serum Leptin Levels in Humans , 2022 .