leptin and Retinal-Diseases

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, hypogenitalism and renal defects. Recent findings have associated the etiology of the disease with cilia, and BBS proteins have been implicated in trafficking various ciliary cargo proteins. To date, 17 different genes have been reported for BBS among which BBS1 is the most common cause of the disease followed by BBS10, and BBS4. A murine model of Bbs4 is known to phenocopy most of the human BBS phenotypes, and it is being used as a BBS disease model. To better understand the in vivo localization, cellular function, and interaction of BBS4 with other proteins, we generated a transgenic BBS4 mouse expressing the human BBS4 gene under control of the beta actin promoter. The transgene is expressed in various tissues including brain, eye, testis, heart, kidney, and adipose tissue. These mice were further bred to express the transgene in Bbs4 null mice, and their phenotype was characterized. Here we report that despite tissue specific variable expression of the transgene, human BBS4 was able to complement the deficiency of Bbs4 and rescue all the BBS phenotypes in the Bbs4 null mice. These results provide an encouraging prospective for gene therapy for BBS related phenotypes and potentially for other ciliopathies.

Topics: Animals; Bardet-Biedl Syndrome; Cilia; Disease Models, Animal; Female; Gene Expression; Genotype; Humans; Hydrocephalus; Infertility, Male; Kidney; Leptin; Male; Mice; Mice, Knockout; Mice, Transgenic; Microtubule-Associated Proteins; Obesity; Phenotype; Proteins; Retinal Diseases; Sympathetic Nervous System; Testis; Transgenes

The purpose of this study was to investigate the relationship between vitreous leptin levels and retinal diseases.. Levels of vitreous leptin were evaluated in proliferative diabetic retinopathy (PDR) and a variety of other retinopathies including: macular disease, neovascular maculopathies, primary retinal detachments, and vascular occlusive disease.. In patients with PDR (N=7), the average vitreous level of leptin (37.4 ng/ml) was significantly higher than that in patients with PVR (<1.0 ng/ml, P<0.05). Vitreous leptin level in patients with PVR or macular disease (N=18), with or without diabetes, was not significantly different from the control subjects who had retinal detachment only (N=7).. The results show that the leptin level in vitreous taps is elevated in PDR. We suggest that leptin plays an active role in PDR.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Prognosis; Retinal Diseases; Severity of Illness Index; Vitrectomy; Vitreous Body

Previous studies have demonstrated that elevated plasma leptin concentrations are associated with essential hypertension. It has also recently been shown that leptin plays a promoting role in angiogenesis, and the vascular endothelium expresses the long form of leptin receptor. Those data led us to hypothesize that leptin might contribute to end-organ damage in hypertension. Thus, in the present study we evaluated the relationship between plasma leptin concentrations and hypertensive retinopathy (HR). One hundred and eleven patients newly diagnosed with essential hypertension [EHT; mean age, 43.5 +/-10.7 yr; body mass index (BMI), 28.1 +/- 4.4 kg/m2; male/female ratio, 71/40] and 79 healthy normotensive control subjects (NT; mean age, 43.6 +/- 9.2 yr; BMI, 28.2 +/- 3.3 kg/m2; male/female ratio, 50/29) were enrolled in the study. For the assessment of retinopathy according to the Keith-Wagener classification, direct and indirect ophthalmoscopy were performed in all subjects after dilatation of the pupils. Plasma leptin levels were significantly higher in EHT (11.8 +/- 11.1 ng/mL) than in NT (7.2 +/- 5.1 ng/mL) (P = 0.003). Plasma leptin concentrations were strongly correlated with BMI in both EHT (r = 0.45; P = 0.001) and NT (r = 0.38; P = 0.001) groups. Plasma leptin in patients with grade 2 HR (24.8 +/- 15.8 ng/mL; n = 22) was significantly higher than that in patients with grade 1 HR (16.1 +/- 4.9 ng/mL; n = 29; P = 0.001), grade 0 HR (5.1 +/- 3.1 ng/mL; n = 60; P = 0.001), and NT (P = 0.001). Plasma leptin in patients with grade 1 HR was also significantly higher than that in patients without retinopathy (P = 0.001) or in NT (P = 0.001). The estimated threshold of plasma leptin concentration for HR was 10.2 ng/mL. This critical leptin level served largely to separate patients with retinopathy from those without retinopathy. In summary, our results show that plasma leptin concentrations increase progressively with higher grades of hypertensive retinopathy even after correction for BMI, suggesting that a critical leptin level is needed for the development of retinopathy. Elevated concentrations of plasma leptin might be secondary to release of leptin by the vascular endothelium damaged by high blood pressure, as an epiphenomenon. However, a pathogenic role for leptin in hypertensive retinopathy cannot be excluded.

Topics: Adult; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Ophthalmoscopy; Reference Values; Retinal Diseases