Retinal arterial remodeling in patients with pheochromocytoma or paraganglioma and its reversibility following surgical treatment.

OBJECTIVE: Structural abnormalities in resistance arteries are a hallmark of patients with hypertension. In hypertensive patients with pheochromocytoma or paraganglioma (PPGL), it is still a matter of debate whether structural vascular changes are because of elevated blood pressure (BP) or to toxic effects of elevated circulating catecholamines. Hence, the aim of our study was to assess whether catecholamine excess and/or elevated BP affect the structure of small retinal arteries in patients with catecholamine-producing tumors. METHODS: The study included 27 patients with PPGL and 27 hypertensive patients. All patients underwent biochemical tests for catecholamine excess, echocardiography and analyses of scanning-laser-Doppler-flowmetry (SLDF) both at baseline and 12 months following surgical resection of PPGL. RESULTS: Baseline retinal arterial diameter, arterial wall thickness and wall cross sectional area (WCSA) were higher in patients with PPGL as compared with subjects without PPGL (arterial diameter: 110 ±â€Š16.5 vs. 99.5 ±â€Š10.8 µm, wall thickness: 16.3 ±â€Š6.0 vs. 13.5 ±â€Š4.0 µm, WCSA: 4953.9 ±â€Š2472.8 vs. 3784.1 ±â€Š1446.3 µm, P < 0.05). Significant correlations were noted between wall thickness and WCSA and echocardiographic parameters assessing diastolic and systolic function of left ventricle. No correlations between retinal parameters, BP level and plasma concentrations of metanephrines were observed. In patients with PPGL, there were postoperative decreases in wall thickness (16.4 ±â€Š15.8 vs. 14.8 ±â€Š4.7 µm; P = 0.011) and WLR (0.42 ±â€Š0.13 vs. 0.37 ±â€Š0.10; P = 0.003) at 12 months after surgical removal of tumors. CONCLUSION: This is the first study to demonstrate that catecholamine excess is related to thickening of retinal arteries independent of BP and reversible after surgical cure. These data support a role of catecholamines in vascular remodeling in PPGL patients.

Fuchs Endothelial Corneal Dystrophy: Strong Association with rs613872 Not Paralleled by Changes in Corneal Endothelial TCF4 mRNA Level.

Fuchs endothelial corneal dystrophy (FECD) is a common corneal endotheliopathy with a complex and heterogeneous genetic background. Different variants in the TCF4 gene have been strongly associated with the development of FECD. TCF4 encodes the E2-2 transcription factor but the link between the strong susceptibility locus and disease mechanism remains elusive. Here, we confirm a strong positive association between TCF4 single nucleotide polymorphism rs613872 and FECD in Polish patients (OR = 12.95, 95% CI: 8.63-19.42, χ (2) = 189.5, p < 0.0001). We show that TCF4 expression at the mRNA level in corneal endothelium (n = 63) does not differ significantly between individuals with a particular TCF4 genotype. It is also not altered in FECD patients as compared to control samples. The data suggest that changes in the transcript level containing constitutive TCF4 exon encoding the amino-terminal part of the protein seem not to contribute to disease pathogenesis. However, considering the strong association of TCF4 allelic variants with FECD, genotyping of TCF4 risk alleles may be important in the clinical practice.

Polymorphisms of the homologous recombination gene RAD51 in keratoconus and Fuchs endothelial corneal dystrophy.

PURPOSE: We investigated the association between genotypes and haplotypes of the c.-61G>T (rs 1801320) and c.-98G>C (rs 1801321) polymorphisms of the RAD51 gene and the occurrence of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) in dependence on some environmental factors. METHODS: The polymorphisms were genotyped in peripheral blood lymphocytes of 100 KC and 100 FECD patients as well as 150 controls with PCR-RFLP. RESULTS: The G/T genotype of the c.-61G>T polymorphism was associated with significantly increased frequency occurrence of KC (crude OR 2.99, 95% CI 1.75-5.13). On the other hand, the G/G genotype of this polymorphism was positively correlated with a decreased occurrence of this disease (crude OR 0.52, 95% CI 0.31-0.88). We did not find any correlation between genotypes/alleles of the c.-98G>C polymorphism and the occurrence of KC. We also found that the G/G genotype and G allele of the c.-98G>C polymorphism had a protective effect against FECD (crude OR 0.51, 95% CI 0.28-0.92; crude OR 0.53, 95% CI 0.30-0.92, resp.), while the G/C genotype and the C allele increased FECD occurrence (crude OR 1.85, 95% CI 1.01-3.36; crude OR 1.90, 95% CI 1.09-3.29, resp.). CONCLUSIONS: The c.-61T/T and c.-98G>C polymorphisms of the RAD51 gene may have a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.