Danuta Karczewicz

Publications of Danuta Karczewicz

• Neural stem/progenitor cells circulating in peripheral blood of patients with neovascular form of AMD: a novel view on pathophysiology.

  Authors: Anna Machalińska, Patrycja Kłos, Krzysztof Safranow, Violetta Dziedziejko, Michał Rudnicki, Edyta Paczkowska, Danuta Karczewicz, Bogusław Machaliński

  Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie. 08/2011; 249(12):1785-94.

  The neovascular form of age-related macular degeneration (AMD) manifested with choroidal neovascularization (CNV) is one of the leading causes of rapid and irreversible visual loss. Recent reportsThe neovascular form of age-related macular degeneration (AMD) manifested with choroidal neovascularization (CNV) is one of the leading causes of rapid and irreversible visual loss. Recent reports suggest that bone marrow-derived stem/progenitor cells (SPCs) play a crucial role in the development and progression of the disease. The purpose of this study was to investigate whether or not undifferentiated non-haematopoietic stem cells, including those capable of differentiating into neural phenotypes, play a role in the pathological state of CNV formation. Peripheral blood samples were collected from 46 patients diagnosed with CNV and from 46 controls. The CXCR4(+)Lin(-)CD45(-) stem cells were counted and analysed by flow cytometry. Using qRT-PCR and immunocytofluorescence, the expression of early neural and glial cell markers (β-III-tubulin, nestin, and glial fibrillary acidic protein) in the sorted cells was analysed, and correlated with plasma concentrations of stromal cell-derived factor 1 (SDF-1) (enzyme-linked immunosorbent assay), which is a pivotal chemokine that regulates the trafficking of SPCs. We found that the number of circulating CXCR4(+)Lin(-)CD45(-) cells did not differ in patients with active CNV as compared to the controls. However, we noticed significant intracellular overexpression of β-III-tubulin in the cells derived from AMD patients. Moreover, we observed significantly lower SDF-1 plasma levels in neovascular AMD patients compared to healthy individuals. Our findings suggest that neural progenitor cells, together with low SDF-1 concentrations, may play a considerable role in the process of AMD progression. Further investigations aimed at the precise elucidation of these issues may help with the future development of effective prevention against, and the treatment of, this disease.

• Influence of ranibizumab on vascular endothelial growth factor plasma level and endothelial progenitor cell mobilization in age-related macular degeneration patients: safety of intravitreal treatment for vascular homeostasis.

  Authors: Anna Machalińska, Edyta Paczkowska, Tomasz Pabin, Krzysztof Safranow, Danuta Karczewicz, Boguslaw Machaliński

  Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 08/2011; 27(5):471-5.

  Intravitreal ranibizumab, which neutralizes vascular endothelial growth factor (VEGF), nowadays constitutes the first-line treatment in neovascular age-related macular degeneration (AMD). However,Intravitreal ranibizumab, which neutralizes vascular endothelial growth factor (VEGF), nowadays constitutes the first-line treatment in neovascular age-related macular degeneration (AMD). However, its potential systemic effect on vascular homeostasis as the consequence of such therapy has not been extensively investigated. Peripheral blood (PB) samples from 12 patients with newly diagnosed neovascular AMD were analyzed before as well as 1 and 4 weeks after intravitreal treatment with ranibizumab. VEGF plasma levels, the number of circulating endothelial progenitor cells (EPCs), and the intracellular expression of hypoxia-inducible factor (HIF) in PB cells were determined by enzyme-linked immunosorbent assay, flow cytometry, and real-time quantitative reverse transcriptase-polymerase chain reaction assays, respectively. No significant changes within the analyzed parameters were found in the first or fourth weeks after ranibizumab injection compared with the primary, basic values before treatment. Based on our findings, intravitreal ranibizumab does not induce significant systemic effects or vascular impairment. Evaluation of the VEGF plasma level, the PB EPC concentration, and intracellular HIF expression may be supportive indicators of drug safety for ranibizumab.

• Stem Cells are mobilized from the bone marrow into the peripheral circulation in response to retinal pigment epithelium damage--a pathophysiological attempt to induce endogenous regeneration.

  Authors: Anna Machalińska, Patrycja Kłos, Bartłomiej Baumert, Magdalena Baśkiewicz, Miłosz Kawa, Michał Rudnicki, Wojciech Lubiński, Barbara Wiszniewska, Danuta Karczewicz, Bogusław Machaliński

  Current eye research. 07/2011; 36(7):663-72.

  Stem cell regeneration of damaged tissue has recently been reported in many different organs. Here, we investigated the mobilization of different stem/progenitor cell (SPC) populations into theStem cell regeneration of damaged tissue has recently been reported in many different organs. Here, we investigated the mobilization of different stem/progenitor cell (SPC) populations into the peripheral blood (PB), their subsequent homing to the injured retina (IR) and contribution to its regeneration in a retinal pigment epithelium (RPE) damage model induced by sodium iodate (NaIO(3)). Mobilization of SPCs was evaluated by flow cytometry. SPCs distribution in IR was assessed using bone marrow (BM)-derived GFP(+)Lin(-) cells transplanted intravenously into NaIO(3)-treated C57Bl/6 mice. The quantity of the chemokine SDF-1 in PB and IR was measured by ELISA and qRT-PCR, respectively. Apoptosis (TUNEL assay), cell proliferation (PCNA analysis) as well as functional retinal activity (electroretinogram) were examined at several time points after NaIO(3) administration. Mobilization of SPCs along with the highest cell proliferation and massive apoptosis within IR were observed on the third day after NaIO(3) administration. Similarly, donor GFP(+)Lin(-) cells were detected in the retina as soon as day 4 after NaIO(3) injection. Plasma levels of SDF-1 did not differ significantly in mice exposed to NaIO(3) compared to healthy controls, however mRNA for SDF-1 was overexpressed locally in IR. Functional retinal recovery was not achieved. Our study provides evidence that BM SPCs egress into PB and home to the injured retina, but are not capable of restoring its function. These results indicate that if the range of retinal destruction is profound, endogenous regeneration is ineffective and may ultimately require adjuvant therapeutic transplantation of specific SPCs subpopulations.

• [Cases of congenital eye malformations in children].

  Authors: Monika Modrzejewska, Ewelina Lachowicz, Danuta Karczewicz

  Annales Academiae Medicae Stetinensis. 01/2011; 57(1):17-25.

  The aim of this work was to present a clinical picture of congenital defects in the anterior and posterior segment of the eye and coexisting systemic developmental anomalies in a group of childrenThe aim of this work was to present a clinical picture of congenital defects in the anterior and posterior segment of the eye and coexisting systemic developmental anomalies in a group of children during the infantile period. We performed a retrospective analysis in a group of 1507 infants seen at our outpatient ophthalmology clinic in 2006-2010. Attention was focused on case histories of nine children (0.6%) with congenital defects of the eye. A routine ophthalmologic examination was done and photographs of the anterior and posterior segment of the eye were archived with the Ret - Cam II apparatus. Maternal risk factors during pregnancy and the perinatal period were analyzed, as well as genetic, familial, infectious, traumatic, metabolic, and toxic factors, and drugs which could have contributed to the pathology of the organ of vision. Additionally, congenital polydysplasia was confirmed using ultrasonography, radiography, and imaging techniques (USG, X-ray, MRI). Congenital anomalies of the anterior and posterior segment of the eye were identified in the study group. Abnomalities of the anterior segment of the eye in four infants were in the form of congenital corneal anomalies (keratopathy, microcornea, sclerocornea, congenital mesenchymal dysgenesis), coloboma of the iris, and aniridia. Additionally, ectopic pupil, congenital cataract, aplasia of the lacrimal point, and palpebral coloboma were observed. Developmental anomalies of the posterior segment of the eye in the form of persistent hyperplastic primary vitreous body or primary fetal vasculature syndrome (PHVB or PFVS), choroid coloboma, coloboma of the optic nerve, and optic disc fovea were recognized in eight children. Anomalies of the anterior and posterior segment of the eye were observed in three children and were associated with microphthalmia, nystagmus, and strabismus. Moreover, systemic anomalies coexisting with ophthalmologic defects were confirmed in 6 children. They were seen in the heart (patent ductus arteriosus (PDA), patent foramen ovale (Pfo), atrial septal defect (ASD), nervous system (aplasia of the corpus callosum, hydrocephalus), osteoarticular system (talipes equinovarus, bifurcate rib, butterfly vertebra, dysmorphic splanchnocranium, contracture of the fingers), genitourinary system (cryptorchism, Wilms' tumor, vesicoureteral reflux grade IV), auditory organ (microtia, aplasia of the external auditory meatus, tympanic cavity, and internal ear), and skin (telangiectasia, syndactyly, appendages, and vegetations). Genetic tests revealed one case of an abnormal karyotype (49, XXXXX). Infections, metabolic disorders, and intoxications were excluded as the background for the anomalies. The finding of a congenital eye anomaly should be followed by a search for other systemic anomalies. Developmental anomalies of the eye and other organs will require a multidisciplinary approach to treatment and care.

• Visual outcomes three and six months after implantation of diffractive and refractive multifocal IOL combinations.

  Authors: Wojciech Lubiński, Karolina Podboraczyńska-Jodko, Jolanta Gronkowska-Serafin, Danuta Karczewicz

  Klinika oczna. 01/2011; 113(7-9):209-15.

  To evaluate 3 and 6 months binocular visual outcomes after cataract surgery using a multifocal IOL "mix and match" approach, with a refractive (ReZoom) IOL in the dominant eye and a diffractiveTo evaluate 3 and 6 months binocular visual outcomes after cataract surgery using a multifocal IOL "mix and match" approach, with a refractive (ReZoom) IOL in the dominant eye and a diffractive (Tecnis) IOL in the fellow eye. Three and 6 months after bilateral cataract surgery, 40 eyes of 20 patients were evaluated for binocular UDVA, UNVA and UIVA (logMAR), spectacle independence, contrast sensitivities (CS), stereoscopic vision, subjective symptoms, patient satisfaction and complications. Three months after surgery mean binocular UDVA did not differ from the six-month follow-up (-0.13 +/- 0.08 vs. -0.18 +/- 0.08; p = NS ). All patients achieved binocular UNVA of 0.0 at both follow-ups. Mean binocular UIVA improved significantly from 0.06 to 0.01 (p<0.027), 6 months after surgery. All patients had very function at good visual all distances and were totally spectacle independent. CS under various conditions was within normal age-matched limits at both follow-ups. For some spatial frequencies six months postoperative results were significantly better than for the 3 months follow-up (p<0.05). Stereoscopic vision was normal. A low degree of glare/halo was detected in 75% of subjects. Overall patient satisfaction was very high (9.6/10). There were no postoperative complications. Mixing and matching multifocal IOLs in selected cataract patients provides an excellent visual outcome, a high level of patient satisfaction and spectacle-free visual function. A period of neuroadaptation lasting at least six months is necessary to obtain better visual function results.

• [Elevated level of circulating endothelial cells as an exponent of chronic vascular dysfunction in the course of AMD].

  Authors: Anna Machalińska, Krzysztof Safranow, Zofia Sylwestrzak, Krzysztof Szmatłoch, Leszek Kuprjanowicz, Danuta Karczewicz

  Klinika oczna. 01/2011; 113(7-9):228-32.

  In recent years, emerging data support the concept of endothelial dysfunction in the course of age-related macular degeneration (AMD). Circulating endothelial cells (CECs) are desquamated matureIn recent years, emerging data support the concept of endothelial dysfunction in the course of age-related macular degeneration (AMD). Circulating endothelial cells (CECs) are desquamated mature cells that have detached from the intimal monolayer in response to endothelial injury. In this study we sought to explore the potential role of endothelial dysfunction in pathogenesis of AMD by measuring the concentration of CECs in peripheral blood of AMD patients. Peripheral blood samples from 31 patients with diagnosed dry AMD and 46 patients with neovascular AMD were collected. Forty six, age- and sex-matched volunteers without AMD were enrolled as a control group. CECs were counted and analyzed by flow cytometry. Multivariate analyses of patients and controls adjusted for age, gender, presence of ischemic heart disease, hypertension and smoking (current or past) revealed that both wet (beta = +0.45, p = 0.0003) and dry (beta = +0.28, p = 0.027) forms of AMD are independent factors associated with higher number of CECs. Our results suggest that there is an endothelial alteration accompanying AMD. Increased numbers of CECs AMD patients reflect a severe vascular disturbance and may contribute to the disease process. These findings can help expand our knowledge of the pathogenic mechanisms of AMD and may be relevant to the potential treatment of this disease.

• [Combined photodynamic therapy and intravitreal injection of triamcinolone acetonide in patients with wet form of AMD. Introductory report].

  Authors: Katarzyna Mozolewska-Piotrowska, Karol Krzystolik, Danuta Karczewicz, Monika Drobek-Słowik, Katarzyna Kubasik-Kładna

  Klinika oczna. 01/2011; 113(7-9):233-6.

  To evaluate the efficacy of combined PDT and 4 mg intravitreal triamcinolone acetonide injection, performed 48-72 hours after PDT, in patients with wet form of AMD. Nonrandomised, interventional caseTo evaluate the efficacy of combined PDT and 4 mg intravitreal triamcinolone acetonide injection, performed 48-72 hours after PDT, in patients with wet form of AMD. Nonrandomised, interventional case series, 13 eyes of 13 patients with subfoveal CNV due to AMD that did not respond to PDT monotherapy - 7 females, 6 males - at the age of 65-85 (average age 76.6 +/- 6.7 years); standard PDT was performed in all patients followed by a 4 mg intravitreal injection of triamcinolone acetonide given 48-72 hours after PDT. Follow up visits were scheduled 1 and 7 days after the injection and then every 3 months afterwards and included: BVCA (Snellen chart), IOP measurements, FA, OCT, slit lamp and eye fundus examination. Lesions with active CNV leakage in FA were retreated every 3 months. Average observation time was 10.8 +/- 3.5 months. Baseline visual acuity before PDT monotherapy was applied (Vo) was 0.17 +/- 0.12 (0.06-0.5), and after the therapy decreased to (V1) 0.14 +/- 0.13 (0.05-0.2). After combined PDT and Tc treatment BVCA increased to (V2) 0.21 +/- 0.13 (0.06-0.5), p<0,03. 76,9% of patients gained or maintained visual acuity after combined therapy in the observation time. In 70% of eyes no signs of active CNV was observed in AF and OCT after 1 session of combined PDT and Tc treatment. Only 4 patients required 1 repeated treatment session. 1. Combination of PDT and IVTA may be effective in patients with wet AMD with no response to PDT alone and significantly reduces the repeated treatment rate. 2. Intravitreal Tc injection performed 48-72 hours after PDT may improve the final functional effects in treated eyes as compared with PDT monotherapy. Our results need further investigation.

• Chorioretinitis in infants.

  Authors: Monika Modrzejewska, Ewelina Lachowicz, Danuta Karczewicz, Alicja Zdanowska

  Klinika oczna. 01/2011; 113(10-12):352-6.

  The aim of this review is to present cases of chorioretinitis in infants caused by viral and parasitic infections. Four infants with viral chorioretinitis were identified in a routineThe aim of this review is to present cases of chorioretinitis in infants caused by viral and parasitic infections. Four infants with viral chorioretinitis were identified in a routine ophthalmological examination. Laboratory tests towards bacterial, viral and parasitic diseases were performed. Toxoplasmosis, rubella, and CMV infections were diagnosed in clinical and laboratory tests. After a wide spectrum of therapy a total remission of inflammatory process in all the discussed children was observed. Posterior uveitis is an ocular complication which can be connected with viral or parasitic infections in postnatal period. Prematurity, normal delivery, intrauterine transmission, breast feeding, comorbid diseases might be associated with chorioretinitis in infants.

• [Persistent fetal vasculature syndrome--clinical image and diagnostic difficulties].

  Authors: Monika Modrzejewska, Ewelina Lachowicz, Danuta Karczewicz, Ewa Sawińska

  Klinika oczna. 01/2011; 113(10-12):357-63.

  The aim of this review is to present cases of clinically differentiated picture of persistent fetal vasculature syndrome--PFVS (also called persistent hyperplastic primary vitreous body--PHPVB)The aim of this review is to present cases of clinically differentiated picture of persistent fetal vasculature syndrome--PFVS (also called persistent hyperplastic primary vitreous body--PHPVB) observed in group of infants and children. Case records of four children with characteristic changes of posterior form of persistent fetal vasculature syndrome, which were observed on fundus of the eyes, were analyzed retrospectively. Routine ophthalmological examination, genetic, cytogenetic and laboratory tests towards coexisting bacterial, viral and parasitic diseases and congenital anomaly of the eye or chorioretinal neoplastic changes of neonatal period were performed. Ophthalmological changes were archived using Ret-Cam II apparatus (Clarity Medical Systems). Measurement of the axial diameter of the eyes and exclusion coexisting ocular disease by ultrasonography (A-scan US i B-scan US and color Doppler ultrasonography--CDU), were performed. Different clinical image of posterior form of persistent hyperplastic primary vitreous body was observe in ophthalmological examination. Changes such as fibrovascular tissue connecting optic disc (n. II) with ora serrata of the retina coexisting with retinoschisis, retrolental mass or persistent hyaloid artery were observed. Additionally concomitant features in pathological eyes were: iris hypoplasia, corectopia, microphthalmia, congenital cataract, secondary glaucoma, degeneration or retinoschisis and intrvitreous haemorrhage. Strabismus, nystagmus and heart disease in the form of persistent fetal circulation were associated with ophthalmological changes. Inflammatory and genetically determined diseases were excluded in differential diagnosis. The diagnosis of persistent hyperplastic primary vitreous body (PHPVB) was confirmed by characteristic clinical symptoms and results of the additional research. Suggestion of recognition of this syndrome (PHPVB) as well as persistent fetal vasculature syndrome (PFVS) should be implemented diagnostics towards other optic and systemic development defects.

• [Functional improvement of injured retina following the adjuvant stem cell-based therapy. Preliminary report].

  Authors: Anna Machalińska, Wojciech Lubiński, Krzysztof Penkala, Miłosz Kawa, Bartłomiej Baumert, Barbara Wiszniewska, Danuta Karczewicz, Bogusław Machaliński

  Klinika oczna. 01/2011; 113(4-6):117-21.

  The purpose of this study was to appraise the functional response of damaged retina to the stem cell-based therapy in mice. The majority of disorders leading to the irreversible vision loss in theThe purpose of this study was to appraise the functional response of damaged retina to the stem cell-based therapy in mice. The majority of disorders leading to the irreversible vision loss in the developed world is caused by retinal degeneration. Since, recent reports emphasized regenerative potential of bone marrow stem marrow stem/progenitor cells (SPCs), we investigated here the beneficial effect of intravenously administrated SPCs on regeneration of acutely injured retina. Selective chemical injury of murine retinas was induced by intravenous administration of sodium iodate (NalO3) in its toxic dose. Flash electroretinogram (ERG), was performed in different time points after infusion of bone marrow-derived and negative for linage antigens population of SPCs. Stem cell-based therapy resulted in gradual increase of b-wave amplitude in ERG recordings starting from the 3rd day after NalO3 administration, what confirmed the improvement of retinal function in long-term observation. Our preliminary findings revealed that the selected stem cell-based therapy employed in the adjuvant mode has been shown to be effective in supporting the retinal function recovery after acute retinal damage.

• Different populations of circulating endothelial cells in patients with age-related macular degeneration: a novel insight into pathogenesis.

  Authors: Anna Machalinska, Krzysztof Safranow, Violetta Dziedziejko, Katarzyna Mozolewska-Piotrowska, Edyta Paczkowska, Patrycja Klos, Ewa Pius, Katarzyna Grymula, Barbara Wiszniewska, Danuta Karczewicz, Boguslaw Machalinski

  Investigative ophthalmology & visual science. 01/2011; 52(1):93-100.

  Circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) may serve as novel markers of endothelial dysfunction. The presence and clinical implications of CECs and the expressionCirculating endothelial cells (CECs) and endothelial progenitor cells (EPCs) may serve as novel markers of endothelial dysfunction. The presence and clinical implications of CECs and the expression of endothelin (ET)-1, one of the most potent vasoconstrictors, have not been evaluated in patients with the neovascular form of age-related macular degeneration (AMD). This study was conducted to determine the different populations of endothelial cells (ECs) in the peripheral blood of AMD patients and to correlate these findings with the expression of ET-1 and the cytokines and growth factors responsible for EC migration and function. Peripheral blood samples were collected from 29 patients with diagnosed neovascular AMD and from 38 healthy control subjects. CD133(-)CD144(+) CECs and CD34(+)CD133(+)CD144(+) EPCs were counted and analyzed by flow cytometry. The intracellular expression of ET-1 in peripheral blood nuclear cells (PBNCs) was studied by using qRT-PCR, Western blot, and immunocytofluorescence assays, and ET-1, IGF-1, VEGF, SDF-1, and HGF plasma concentrations were measured in enzyme-linked immunosorbent assays. Increased CECs and EPCs were found in the AMD patients compared with the counts in healthy individuals. The expression of intracellular ET-1 was significantly elevated in PBNCs from the AMD patients compared with the control subjects. In addition a significantly higher plasma concentration of IGF-1 was observed, but a lower SDF-1 level in the group of AMD patients. These findings suggest that circulating endothelial cells, together with high ET-1 content, may contribute to the development of AMD. Further prospective investigations on the mechanism involved may be relevant to the potential treatment of this disease.

• Sodium iodate selectively injuries the posterior pole of the retina in a dose-dependent manner: morphological and electrophysiological study.

  Authors: Anna Machalińska, Wojciech Lubiński, Patrycja Kłos, Miłosz Kawa, Bartłomiej Baumert, Krzysztof Penkala, Ryszard Grzegrzółka, Danuta Karczewicz, Barbara Wiszniewska, Bogusław Machaliński

  Neurochemical research. 11/2010; 35(11):1819-27.

  Sequential morphological and functional features of retinal damage in mice exposed to different doses (40 vs. 20 mg/kg) of sodium iodate (NaIO(3)) were analyzed. Retinal morphology, apoptosis (TUNELSequential morphological and functional features of retinal damage in mice exposed to different doses (40 vs. 20 mg/kg) of sodium iodate (NaIO(3)) were analyzed. Retinal morphology, apoptosis (TUNEL assay), and function (electroretinography; ERG) were examined at several time points after NaIO(3) administration. The higher dose of NaIO(3) caused progressive degeneration of the whole retinal area and total suppression of scotopic and photopic ERG. In contrast, the lower dose induced much less severe degeneration in peripheral part of retina along with a moderate decline of b- and a-wave amplitudes in ERG, corroborating the presence of regions within retina that retain their function. The peak of photoreceptor apoptosis was found on the 3rd day, but the lower dose induced more intense reaction within the central retina than in its peripheral region. In conclusion, these results indicate that peripheral area of the retina reveals better resistance to NaIO(3) injury than its central part.

• Circulating stem cell populations in preterm infants: implications for the development of retinopathy of prematurity.

  Authors: Anna Machalinska, Monika Modrzejewska, Maciej Kotowski, Violetta Dziedziejko, Magda Kucia, Milosz Kawa, Krzysztof Safranow, Magdalena Baskiewicz-Masiuk, Anna Modrzejewska, Danuta Karczewicz, Jacek Rudnicki, Boguslaw Machalinski

  Archives of ophthalmology. 10/2010; 128(10):1311-9.

  To investigate the association among different circulating stem cell (SC) populations, the levels of selected growth factors and chemokines regulating SC migration in the peripheral blood, and theTo investigate the association among different circulating stem cell (SC) populations, the levels of selected growth factors and chemokines regulating SC migration in the peripheral blood, and the incidence of retinopathy of prematurity (ROP). We evaluated 88 participants in this study: 29 preterm infants with ROP, 29 preterm infants without ROP, and 30 healthy full-term infants. Peripheral blood samples collected 10 weeks after delivery were analyzed using flow cytometry, immunofluorescence, real-time reverse transcriptase-polymerase chain reaction, and enzyme-linked immunosorbent assay. The following cell populations were analyzed: (1) lin⁻CXCR4(+)CD45⁻ (enriched in very small embryonic-like SCs), (2) lin⁻CXCR4(+)CD45(+) (enriched in hematopoietic SCs), and (3) CD34(+)CD133(+)CD144(+) (early endothelial progenitor cells) [lin indicates lineage]. The concentrations of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and stromal cell-derived factor 1 were measured in the plasma. The very small embryonic-like SCs and early endothelial progenitor cells expressing neural and endothelial markers were significantly increased in the preterm infants. The number of early endothelial progenitor cells in the peripheral blood was significantly greater in the preterm infants with ROP than in the preterm infants without ROP. An accompanying increase in the concentrations of vascular endothelial growth factor and hepatocyte growth factor was found in the peripheral blood of the preterm infants with ROP. No significant associations were found between hematopoietic SCs and ROP or prematurity. The increased number of early endothelial progenitor cells along with elevated levels of vascular endothelial growth factor and hepatocyte growth factor in preterm infants with ROP suggest that circulating vasculogenic factors may play a role in the development and progression of ROP. The increased number of very small embryonic-like SCs in preterm infants suggests that the development of immature tissues and organs, including the retina, may require a contribution of circulating SCs.

• Refractive status and ocular axial length in preterm infants without retinopathy of prematurity with regard to birth weight and gestational age.

  Authors: Monika Modrzejewska, Wilhelm Grzesiak, Danuta Karczewicz, Daniel Zaborski

  Journal of perinatal medicine. 05/2010; 38(3):327-31.

  To obtain ultrasonographic measurements of ocular axial length (AL) in preterm infants without retinopathy of prematurity (ROP) but with different refractive power in regard to birth weight (BW) andTo obtain ultrasonographic measurements of ocular axial length (AL) in preterm infants without retinopathy of prematurity (ROP) but with different refractive power in regard to birth weight (BW) and gestational age (GA). Refraction was measured after cycloplegia (at 6 months of life) in 350 eyes of 180 preterm (non-astigmatic) infants without ROP. Subjects were grouped according to the refractive error: A [above -6.0 dioptres (D)]; B (-3.1 to -6.0 D); C (0 to -3.0 D); D (0.1 to +3.0 D); E (+3.1 to +6.0 D); F (above +6.0 D). The AL measurement was performed by ocular A-scan ultrasound biometry (10 MHz probe). The longest AL was found in group B (20.62 mm) compared to group D and E (19.35, 19.28 mm; P< or =0.01) and group F and A (19.63, 19.39 mm; P< or =0.05). Only regressive correction for BW was statistically significant. Correlations between AL and BW (Rs=0.23) or GA (Rs=0.17) were found only in group E. AL of myopic eyes was significantly longer. In general, hyperopia was positively correlated with BW, whereas correlation between myopia and BW or GA was not found.

• Ophthalmological and electrophysiological features of Parkinson's disease.

  Authors: Barbara Nowacka, Wojciech Lubiński, Danuta Karczewicz

  Klinika oczna. 01/2010; 112(7-9):247-52.

  Based on available literature, the authors describe the most frequent ocular diseases and symptoms, as well as bioelectrical dysfunction of the visual pathway in patients with Parkinson's diseaseBased on available literature, the authors describe the most frequent ocular diseases and symptoms, as well as bioelectrical dysfunction of the visual pathway in patients with Parkinson's disease (PD). Data published in literature available in PubMed library. The most often ocular diseases, symptoms and the bioelectrical dysfunction were diagnosed using routine ophthalmological examination including tear film tests, perimetry, optical coherence tomography (OCT), color and contrast sensitivity tests, and electrophysiological recordings like EOGs, flash, pattern and multifocal ERGs, VEPs. The most frequent ocular diseases in PD are dry eye syndrome and glaucoma. At least 25% of PD patients manifest visual hallucinations. The most prominent bioelectrical dysfunction of the visual pathway was observed in outer layers of the retina (retinal pigmented epithelium, phoptreceptors) and it was registered mainly in EOG, PERG and mfERG tests. During examination of PD patents, general ophthalmologists should especially pay attention to diagnosis and treatment of glaucoma and dry eye syndrome. In PD visual deficits may occur without any noticeable changes in the routine ophthalmological examination. Electrophysiological recordings can explain, at least partially, visual dysfunction in course of PD.

• Associations between high myopia and class II HLA.

  Authors: Maria Zejmo, Damian Czepita, Andrzej Mikłaszewicz, Olimpia Sipak-Szmigiel, Aneta Dołubeczko, Danuta Karczewicz, Stefania Giedrys-Kalemba

  Acta ophthalmologica. 12/2009;

• Ocular circulation in systemic lupus erythematosus.

  Authors: Monika Modrzejewska, Lidia Ostanek, Danuta Bobrowska-Snarska, Danuta Karczewicz, Grazyna Wilk, Marek Brzosko, Alon Harris

  Medical science monitor : international medical journal of experimental and clinical research. 11/2009; 15(11):CR573-8.

  BACKGROUND: Mean vascular resistance in the retrobulbar arteries of SLE patients and the statistical relationship between its parameters and the presence of certain antibodies were determined.BACKGROUND: Mean vascular resistance in the retrobulbar arteries of SLE patients and the statistical relationship between its parameters and the presence of certain antibodies were determined. MATERIAL/METHODS: Forty-three eyes of 43 SLE female patients aged 46.28+/-8.45 years with disease duration of 10.03+/-7.96 years were examined. Physical and ophthalmic examinations with assessments of the immunological markers ANA/IgG-IgM, aCL, anti-beta2GPI, LA, and anti-dsDNA antibodies were performed. color Doppler imaging (CDI) was used in the OA, CRA, LPCA, and MPCA vessels. The vascular resistance indices (RIs) were compared with those of 43 eyes of 43 female controls. Covariance and multiple regression analysis with chi squared, Pearson, Shapiro-Wilk, and Levene tests were used in the statistical analysis (significance levels at p<or=0.01 and p<or=0.05). RESULTS: Significantly increased RIs in the OA, CRA, LPCA, and MPCA were recorded. aCL, abeta2GPI, and LAC correlated significantly with increased RI in the CRA. SLE diagnosis significantly correlated with RI in the OA and PCAs. Significant relationship between age and RI in the CRA and LPCA was detected. CONCLUSIONS: Retrobulbar resistance disturbances were detected in SLE patients by CDI. SLE diagnoses and presence of aPLs antibodies were associated with an increased resistivity index in ophthalmic and retino-choroidal vessels.

• Potential application of adult stem cells in retinal repair--challenge for regenerative medicine.

  Authors: Anna Machalińska, Bartłomiej Baumert, Leszek Kuprjanowicz, Barbara Wiszniewska, Danuta Karczewicz, Bogusław Machaliński

  Current eye research. 09/2009; 34(9):748-60.

  Stem cells (SCs) maintain the balance among somatic cell populations in various tissues and are responsible for organ regeneration. The remarkable progress of regenerative medicine in the last fewStem cells (SCs) maintain the balance among somatic cell populations in various tissues and are responsible for organ regeneration. The remarkable progress of regenerative medicine in the last few years indicates promise for the use of SCs in ophthalmic disorder treatment. This review describes the current view on hierarchy in the SC compartment and presents the latest attempts to use adult SCs in the regeneration of the retina. Research performed primarily in animal models gives hope for using similar strategies in humans. However, the search for the optimal source of SCs for cell therapy continues. We briefly discuss various potential sources of adult SCs that could be employed in regenerative medicine, particularly focusing on recently identified, very small embryonic-like SCs (VSEL-SCs). These cells are even present in the bone marrow and adult tissues of older patients and could be harvested from cord blood. We believe that VSEL-SCs, after the establishment of ex vivo expansion and differentiation protocols, could be harnessed for retina regeneration.

• Elevated Plasma Levels of C3a Complement Compound in the Exudative Form of Age-Related Macular Degeneration.

  Authors: Anna Machalińska, Violetta Dziedziejko, Katarzyna Mozolewska-Piotrowska, Danuta Karczewicz, Barbara Wiszniewska, Bogusław Machaliński

  Ophthalmic research. 06/2009; 42(1):54-59.

  Aim: Recent findings suggest that chronic inflammatory processes play a role in the progression of age-related macular degeneration (AMD). Here we asked whether the development of different forms ofAim: Recent findings suggest that chronic inflammatory processes play a role in the progression of age-related macular degeneration (AMD). Here we asked whether the development of different forms of AMD is connected with the elevation of plasma C3a-desArg concentration. Methods: We recruited 30 subjects with a clinical diagnosis of exudative AMD with newly diagnosed choroidal neovascularization (CNV), 30 subjects with dry AMD and 30 age- and sex-matched volunteers without AMD. The concentration of C3a-desArg complement compound was measured in the subjects' peripheral blood. We evaluated the association between the level of C3a-desArg and age, sex, smoking, atherosclerosis, and hypertension. Results: We found that the levels of C3a-desArg were significantly elevated in patients with exudative AMD compared to the control group. The concentrations of C3a-desArg in patients with dry AMD were similar to those of controls. Additionally, patients and controls with documented atherosclerosis (AS) displayed significantly higher levels of C3a-desArg compared to subjects without AS. Conclusions: Our results suggest an association between systemic complement activation and the development of CNV. Moreover, we found an association of complement activation with atherosclerosis and confirmed the hypothesis that AMD can be a local manifestation of systemic disease.

• [Evaluation of VEGF and IGF-1 plasma levels in preterm infants--potential correlation with retinopathy of prematurity, clinical implications].

  Authors: Anna Machalińska, Monika Modrzejewska, Violetta Dziedziejko, Maciej Kotowski, Krzysztof Safranow, Aleksandra Herbowska, Danuta Karczewicz

  Klinika oczna. 01/2009; 111(10-12):302-6.

  Insulin-like growth factor-1 plays an important role in fetal growth and development, and its level increases with gestational age. The latest reports show that IGF-1 can directly influence theInsulin-like growth factor-1 plays an important role in fetal growth and development, and its level increases with gestational age. The latest reports show that IGF-1 can directly influence the production of VEGF and regulate the development of blood vessels. Thus, the aim of the study was to evaluate the plasma concentrations of IGF-1 and VEGF as well as analyze their mutual correlation in preterm infants with retinopathy of prematurity (ROP), compared with preterm infants without ROP and full-term babies. To address this issue, peripheral blood samples (PB) were analyzed and collected 10 weeks after delivery from: 25 preterm infants with proliferative stage of retinopathy of prematurity (ROP) and neovascularization (stage 3 or more advanced), 25 preterm infants without ROP, and 25 healthy full-term control infants. Plasma concentrations of VEGF and IGF-1 were measured using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Increased concentrations of VEGF (p < 0.05), were found in the PB of the preterm infants with ROP compared with the preterm babies without retinopathy as well as with the full-term control infants, in whom the lowest levels of the growth factor were observed. The plasma concentrations of IGF-1 in the preterm infants were significantly lower than those of the full-term babies (p < 0.001). After adjustment for gestational age as a independent variable, a tendency to higher concentrations of IGF-1 was observed in the preterm infants with ROP. Disturbances in the interactions of VEGF and IGF-1 at early stages of ROP, leading to uncontrolled increases in their levels in the proliferative phase of disease, can play an important role in the pathogenesis of retinopathy of prematurity.