Biomedical subjects

Zbigniew Zagorski

Publications and source records attributed to Zbigniew Zagorski.

10 recordsLinked to original sources

PubMed2006

Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat.

Citicoline and lithium (Li(-)) have been shown to support retinal ganglion cell (RGC) survival and axon regeneration in vitro. Optic nerve crush (ONC) is a model of both brain axonal injury and certain aspects of the glaucomatous degeneration of RGC. We have used this model to quantify protection offered to RGC by these drugs and to determine whether their effects are mediated by enhanced expression of the antiapoptotic protein Bcl-2. Adult rats (6-12 per group) were subjected to ONC accompanied by a contralateral sham operation. Animals were treated intraperitoneally with either vehicle, citicoline sodium (1g/kg daily for up to 7 days and 300 mg/kg daily afterwards), lithium chloride (30 mg/kg daily), or both drugs combined. Fluorogold was injected bilaterally into superior colliculi 1, 5 or 19 days after ONC. Labeled cells were counted under a fluorescence microscope 2 days after tracer injection. In a separate set of experiments the effects of treatments on expression of Bcl-2 in retinas were evaluated by immunohistochemistry. In vehicle-treated animals there was a progressive decrease of RGC density after crush. This decrease was attenuated in citicoline-treated animals 1 week and 3 weeks after the crush. In the lithium-treated group protection was even more pronounced. In animals treated with both drugs RGC protection was similar to that achieved by lithium alone. Bcl-2 immunoreactivity was seen predominantly in retinal ganglion cells. Its increase was recorded in the lithium and citicoline group as well as in animals treated with the combination of both drugs. Both citicoline and lithium protect RGC and their axons in vivo against delayed degeneration triggered by the ONC. Retinoprotective action of both drugs may involve an increase in Bcl-2 expression.

Animals↗

PubMed2005

Comparison between semiautomated kinetic perimetry and conventional Goldmann manual kinetic perimetry in advanced visual field loss.

PURPOSE: To compare quantitatively visual field (VF) results obtained using a new standardized semiautomated kinetic perimetry (SKP) with those obtained by conventional Goldmann manual kinetic perimetry (MKP) in patients with advanced VF loss. DESIGN: Prospective, single-center, observational comparative case series. SUBJECTS AND METHODS: Seventy-seven eligible patients (36 suffering from advanced retinal nerve fiber layer loss, 20 with concentric constriction of the VF, and 21 with hemianopia) were included in the study. One eye of each patient was examined on the same day with MKP and SKP. Three isopters, identical in both tests, were chosen to assess the extent of the VF loss. To compare the location and size of the corresponding isopters obtained with MKP and SKP, intersection areas of superimposed isopters were expressed as a percentage of union areas. MAIN OUTCOME MEASURES: The area and position of isopters for a defined stimulus condition obtained with both methods were compared. Test duration and patients' preference were also evaluated. RESULTS: Isopters obtained with Goldmann MKP enclosed areas smaller by 20% (confidence interval [CI], 12%-27%). The mean intersection area of Goldmann and SKP VFs was 1763.1 square degrees (CI, 1558.6-1967.7) smaller than the union for stimulus III4e over all groups of patients. Semiautomated kinetic perimetry was preferred by 60% of patients with concentric constriction of the VF. Median duration of the examination was 15 minutes and did not differ significantly between the 2 methods. CONCLUSIONS: Our results indicate that SKP isopter shape and size were very comparable to those obtained on the same eyes with MKP. Semiautomated kinetic perimetry may represent a more standardized method of kinetic perimetry, which still takes advantage of perimetrist-patient interaction to diagnose and monitor advanced VF loss in clinical practice.

Adolescent↗

PubMed2004

Retinal neurodegeneration in the DBA/2J mouse-a model for ocular hypertension.

Mice of the DBA/2J strain spontaneously develop complex ocular abnormalities, including glaucomatous loss of retinal ganglion cells (RGC). In the present study ultrastructural features of retinal neurodegeneration in DBA/2J mice of different age (3, 6, 8 and 11 months) are described. By 3 months, RGC apoptosis characterized by electron-dense karioplasm and cytoplasm of ganglion cells was observed. The occurrence of apoptotic ganglion cells peaked at the age of 6 months. Past this age, necrosis characterized by swelling and electron-rare cytoplasm appeared to be the prevailing form of cell death. Müller glia activation increased with age, but there were no signs of leukocyte infiltration. At 8 and 11 months, signs of neoangiogenesis were found both at the ultrastructural level and in clinical examinations. In these older animals myelin-like bodies, most probably representing the intracellular aggregates of phospholipids in irreversibly injured cells, were also seen. Photoreceptor cells were not affected at any age. Our observations suggest that retinal degeneration in the DBA/2J mice does not involve recruitment of blood-borne inflammatory/phagocytosing cells, and that apoptosis is gradually replaced by necrosis as the predominant pathway of RGC death. Retinal degeneration in 3- to 11-month-old DBA/2J mice partially resembles human pigment dispersion syndrome and pigmentary glaucoma with characteristic anterior segment changes and elevation of intraocular pressure. However, neovasculogenesis and myelin-like bodies are observed during aging. Therefore, the DBA/2J model requires judicious interpretation as a glaucoma model.

Age Factors↗

PubMed2004

Expression of kynurenine aminotransferases in the rat retina during development.

The study investigates the cellular expression of kynurenine aminotransferases (KAT I and II) in the rat retina during development. At P1 (the day of birth) and P7 (the 7th day after birth), KAT I expression was observed in the inner plexiform layer (IPL), the fiber layer (FL), and in vertically running processes in the ganglion cell layer (GCL) (but not in the cell bodies). At P14 (the 14th day after birth) a strong KAT I immunoreactivity was observed in Müller cell endfeet. KAT II was expressed in the IPL, the FL, and in cells in the GCL at P1 and P7. From P14 on, KAT II expression in the IPL decreased. Double labeling revealed that KAT I was expressed in Müller cell endfeet, whilst KAT II both on retinal ganglion cells (RGC) and Müller cell endfeet. In conclusion, KAT I and II are present in the rat retina during development. The heterogeneity of the KAT developmental profiles possibly reflects a neuromodulatory role in the retinal differentiation.

Animals↗

PubMed2004

Age-dependent decrease of retinal kynurenate and kynurenine aminotransferases in DBA/2J mice, a model of ocular hypertension.

The study examines age-dependent changes of kynurenic acid (KYNA) content and kynurenine aminotransferases (KAT I and KAT II) celluar expression in the retinas of DBA/2J mice. Retinas were obtained from DBA/2J mice of different ages (3, 6 and 11 months). C57BL6 mice were used as controls. As measured with HPLC, KYNA content decreased (p < 0.01) in the retinas of 6-month-old DBA/2J mice and continued to decrease (p < 0.0074) in the retinas of 11-month-old animals compared to the controls. Immunohistochemistry showed that expression of both KAT I and KAT II decreased markedly in the retinas of 11-month-old DBA/2J mice compared to controls. The impairment in KYNA biosynthesis in the retinas of DBA/2J mice may be one of the mechanisms of retinal neurodegeneration related to ocular hypertension.

Aging↗

PubMed2003

Alterations of kynurenic acid content in the retina in response to retinal ganglion cell damage.

The present study is the first to examine the modulation of retinal kynurenic acid (KYNA) content in response to N-methyl-D-aspartate (NMDA)-induced cell death in adult rat retinal ganglion cells (RGC). Adult Brown Norway rats were intravitreally injected with NMDA or PBS. Surviving RGC were retrogradely labeled with fluorogold and counted in wholemounts of retinas 2, 7 and 14 days after injection. Retinal KYNA content was measured by HPLC at the same time points. RGC numbers decreased significantly 2, 7 and 14 days after NMDA injection if compared to control retinas. KYNA concentration increased significantly two days after NMDA-injection. However, 7 and 14 days after injection retinal KYNA content was found markedly decreased in NMDA-treated eyes as compared to controls. It is conceivable that KYNA deficiency is causally related to the pathology of excitotoxic retinal diseases.

Animals↗

PubMed2003

Ontogenic changes of kynurenine aminotransferase I activity and its expression in the chicken retina.

Kynurenine aminotransferases are key enzymes for the synthesis of kynurenic acid (KYNA), an endogenous glutamate receptor antagonist. The study described here examined ontogenic changes of kynurenine aminotransferase I (KAT I) activity and its expression in the chicken retina. KAT I activity measured on embryonic day 16 (E16) was significantly higher than at all other stages (E12, P0 and P7). Double labeling with antibodies against glutamine synthetase showed that on P7 KAT I was expressed in Müller cell endfeet and their processes in the inner retina. Since KAT I activity is high in the late embryonic stages, it is conceivable that it plays a neuromodulatory role in the retina during the late phase of embryogenesis.

Animals↗

PubMed2002

Changes of kynurenic acid content in the rat and chicken retina during ontogeny.

BACKGROUND: Kynurenic acid (KYNA) is the only known endogenous glutamate receptor antagonist and neuroprotectant. After showing the presence of KYNA and its synthesising enzymes in the adult rat retina, we examined developmental changes of KYNA content in both vascularised rat and avascular chicken retinas. METHODS: Retinas from Brown Norway rats and White Leghorn chickens at different developmental stages between the embryonic and the adult stages were used. KYNA levels were investigated with HPLC. RESULTS: KYNA was present in both rat and chicken retinas during ontogeny. The mean (+/- SE) concentration of KYNA found in the embryonic rat retina (E20) was 95+/-10 pmol/g wet wt. The KYNA content sharply increased within the following 3 days reaching a peak at birth (P0) of 702+/-77 pmol/g wet wt. At the end of the second postnatal week KYNA content decreased to 211+/-29 pmol/g wet wt. A further decrease was observed subsequently, with KYNA levels of 100+/-24.6 pmol/g wet wt at 3 month and 58+/-4 pmol/g wet wt at 12 month. Significant differences in KYNA concentrations between the embryonic and post-hatching stages were also observed in the chicken retina. In 12-day-old embryonic (E12) retinas the KYNA level was 364+/-48 pmol/g wet wt, and in E16 embryos it was 440+/-80 pmol/g wet wt. It significantly decreased to 200+/-38 pmol/g wet wt at P0 and stayed more or less at this level until P21 (217.5+/-23.5 pmol/g wet wt). CONCLUSION: KYNA is present in the rat and chicken retinas in high concentrations during early developmental stages. This suggests that KYNA may play a neuromodulatory role in the retina during development.

Animals↗

PubMedDate not supplied

Content of kynurenic acid and activity of kynurenine aminotransferases in mammalian eyes.

The present study investigated the kynurenic acid (KYNA) contents and kynurenine aminotransferase (KAT I and II) activity in structures of the human, monkey, rabbit and bovine eye. KYNA levels were investigated with HPLC and detected fluorimetrically. The activity of KAT I and II was assayed as quantitative analysis of newly synthesized KYNA in vitro. Mean KYNA levels (+/-SD) in the human retina and vitreous body were 36.8 +/- 7.6 and 33.1 +/- 6.2 pmol/g wet tissue weight, respectively. In human eyes, KAT I activity in the vitreous body was 0.57 +/- 0.28, that of KAT II was 2.56 +/- 0.69. KAT I activity in the retina was 3.42 +/- 1.17 and that of KAT II 10.75 +/- 9.2. (KAT activity is expressed as KYNA synthesis in picomoles per gram wet tissue weight per hour.) The values of KYNA and KAT observed in other mammalian species tested were in the same range. In conclusion, KYNA and KAT enzymatic activity are present in the structures of human and other mammalian eyes.

Animals↗

PubMedDate not supplied

Retinopathy of prematurity: A refresher for obstetricians.

Advances in neonatal care improved the survival of many preterm infants, but also increased the incidence of retinopathy of prematurity (ROP). Numerous risk factors have been associated with the development of ROP, the most important of which are: low birth weight, early gestational age at delivery, and duration of oxygen therapy. Screening premature infants is a critical factor for any prevention and treatment protocol. The Retinopathy of Prematurity Subcommittee of the American Academy of Ophthalmology (AAO) and the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) have developed guidelines that assist practicing physicians in managing children with ROP. A portion of these guidelines is particularly applicable to practicing obstetricians who, along with the pediatricians, are often the primary physicians for the affected families. The aim of this paper is to present a comprehensive overview of the epidemiology, etiology, manifestations, prevention, and management of ROP. In the last section, the authors present guidelines for practicing obstetricians that incorporate the most recent recommendations of ophthalmic and pediatric thought leaders.

Child↗