Mutagenesis of mitochondrial DNA in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is an age-related, slowly progressive disease, which may lead to loss of vision resulting from apoptosis of corneal endothelial (CE) cells, dysfunction of Descemet membrane (DM) and corneal edema. A growing body of evidence suggests that oxidative stress may play a major role in the pathogenesis of FECD and that mitochondria of CE cells are its main target. Mitochondrial DNA (mtDNA) is particularly prone to oxidative stress and changes in mtDNA were reported in FECD patients. In the present work we studied mtDNA damage and repair, mtDNA copy number, and the 4977bp common deletion in mtDNA in DM cells and peripheral blood lymphocytes (PBLs) isolated from FECD patients. PBLs from 35 FECD patients and 32 controls were challenged for 10min with hydrogen peroxide at 20µM and then left in a fresh medium for 3h, resulting in a decrease in mtDNA copy number in both groups. Damage to mtDNA was not fully repaired after 3h and the extent of remaining lesions was significantly higher in the patients than the controls. We observed a higher copy number and an increased extent of mtDNA damage as well as a higher ratio of the common 4977bp deletion in DM cells of FECD patients than the controls. Our results confirm that mutagenesis of mtDNA may be involved in FECD pathogenesis and disturbance in mtDNA sensitivity to damaging agent as well as changes in mtDNA damage repair along with alternations in mtDNA copy number may underline this involvement.

Effect of photodynamic therapy with verteporfin on tumor thickness and best corrected visual acuity in patients with circumscribed choroidal hemangioma: a single-center experience.

The management of circumscribed choroidal hemangioma (CCH) with photodynamic therapy (PDT) using verteporfin has resulted in significant functional and clinical improvement compared with the pre-PDT era. Literature data on factors influencing clinical outcomes and predictors of response to PDT in symptomatic CCH are inconsistent. The aim of this study was to investigate the efficacy of PDT with verteporfin in patients with CCH depending on symptom duration and tumor thickness at baseline. We analyzed the medical records of 37 patients with symptomatic CCH divided into 3 groups according to symptom duration (≤ 50 weeks, 51 - 100 weeks, and > 100 weeks) and into 2 groups according to tumor thickness (≤ 2.3 mm and > 2.3 mm). Patients were subjected to PDT with verteporfin at a concentration of 6 mg/m2 body surface area and a light dose of 50 J/cm2 at a wavelength of 689 nm. The mean number of treatment sessions was 1.57 (range, 1 - 3). Tumor thickness, the transverse and longitudinal diameters of the tumor base, and best corrected visual acuity (BCVA) were evaluated at baseline and at 12 - 15 months after treatment. After PDT, the mean tumor thickness in the whole study group decreased by 1.19 ± 0.66 mm (from 3.14 mm to 1.95 mm). Subgroup analyses revealed no significant differences between the 2 groups divided according to tumor thickness (p = 0.49). However, tumor thickness differed significantly between the 3 groups divided according to symptom duration (p < 0.05). BCVA increased in 22 patients (59.5%), remained unchanged in 12 patients (16.2%), and decreased in 3 patients (10.1%). Our study provides evidence for the efficacy of PDT with verteporfin in terms of improving or stabilizing visual function as well as reducing tumor thickness in patients with CCH, including those with long-lasting disease.

Age dependence of plasma endothelin levels in glaucoma patients.

The aim of the study was to investigate the endothelin-1 (ET-1) plasma level and its age dependence in patients with normal tension glaucoma (NTG), high tension glaucoma (HTG), and healthy controls. In blood samples from 35 NTG patients, 34 HTG patients, and 36 controls, ET-1 plasma levels were determined by enzyme-linked immunosorbent assay (ELISA). After adjustment for age and gender, the mean ET-1 levels were found to be similar in all three study groups. The age dependency however was highest in NTGs and significantly different from that of the controls. For the HTGs, this dependence was weaker and not significantly different from that of the controls. Our findings suggest that age had a significantly greater influence on ET plasma level in the NTG patients than in the HTG patients and controls. This supports previous reports indicating that ET plays a role in the pathogenesis of glaucoma, and in particular normal NTG.

The importance of various factors relating to the morphological quality of corneas used for PKP by the Warsaw Eye Bank from 1996 to 2002.

To examine the effect of various factors such as: donor's age, cause of death, time between death and preservation and duration of preservation on the morphological quality of corneas used for Penetrating Keratoplasty (PKP). Our purpose was to assess the role of the above factors influencing the corneal overall rating and endothelial cell density. The present data regarding the donor's age and time between death and preservation of corneas obtained from eye banks belonging to the European Eye Bank Association and Polish eye banks were compared. Corneoscleral buttons and data concerning donors were obtained by eye bank technicians and collected in Warsaw Eye Bank in the years 1996-2002. The quality of the corneas recovered was evaluated by means of slit lamp Nikon NS-IV and specular microscope KONAN. Cardiorespiratory failure and cardiac arrest were the most frequent cause of the donors' death. In many cases donors with confirmed brain death who were given the corneas, were also donors of internal organs like heart, kidneys, pancreas and liver. The number of donors with disseminated neoplasm disease--complete disadvantage for removing corneas increased during the eye bank activity. The epithelial and endothelial layers sometimes underwent mechanical trauma in the group of donors because of sudden death. From 1996 to 2002 more than 50% of the donors were over 60 years of age. There were many problems with receiving corneas from younger donors. The overall rating tissues which were obtained in a very short time after death (to 5 hours) was higher (Excellent and Very Good) compared with corneas removed 8-12 hours after the donor's death. The increasing percentage of endothelial cell loss was observed in all the corneas after about 7 days of preservation in the medium. The mean endothelial cell density slightly decreased with donor's age, but its suggested range of the factors possibility of finding the corneas with high number of endothelial cell density both in younger and older donors. The average time from death to preservation was similar in eye banks preserving corneas at +4 degrees C (8-10 hours) compared with eye banks using mainly the organ culture method. The rating of the morphological state of corneas suitable for PKP depends on the time between death and preservation, donor's age, cause of death and time of preservation of corneas. Corneas obtained shortly after the donor's death showed a higher endothelial cell density and better overall rating than those removed after relatively longer period after the donor's death. An increasing percentage of endothelial cell loss was observed after 7 days of preservation independent of other factors.