Anna Machalińska

Publications of Anna Machalińska

• Complement system activation and endothelial dysfunction in patients with age-related macular degeneration (AMD): possible relationship between AMD and atherosclerosis.

  Authors: Anna Machalińska, Miłosz P Kawa, Wojciech Marlicz, Bogusław Machaliński

  Acta ophthalmologica. 11/2011;

  Age-related macular degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). First, an association between AS and AMD is apparent from theAge-related macular degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). First, an association between AS and AMD is apparent from the analyses of the histological and biochemical structure of atherosclerotic plaques in the vascular walls and retinal drusen, the hallmark of AMD. Second, there is considerable evidence implicating endothelial dysfunction in the pathogenesis of both disorders, and cellular oxidative stress appears to be a common denominator underlying this process. Moreover, there are observations that the complement system (CS) triggering inflammatory response contributes to the onset and advancement of both diseases. The CS plays a role in the generation of drusen and neovascularization in AMD as well as in vascular endothelium activation, cell damage and ultimately atherosclerotic plaque formation in the course of systemic arteriosclerosis. It is widely recognized that both AMD and AS are not only related to local stimulation of the CS, but also result in its systemic activation. In addition, a specific Y402H polymorphism of the complement inhibitor factor H has been found to be associated with the incidence of both AMD and AS. Here, we propose a linking hypothesis between CS activation, endothelial dysfunction and the pathogenesis of two common and age-related pathological processes, AS and AMD. We also discuss the potential therapeutic value of pharmacological modulation of CS activation in these disorders.

• 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.

• [The role of circulating endothelial progenitor cells in the progression of retinopathy of prematurity--a prospective study].

  Authors: Anna Machalińska, Maciej Kotowski, Krzysztof Safranow, Joanna Lewandowska, Monika Modrzejewska, Jacek Rudnicki, Ryszard Czajka, Bogusław Machaliński

  Klinika oczna. 01/2011; 113(7-9):223-7.

  Retinopathy of prematurity (ROP) is the primary cause of visual impairment in preterm infants. There are available data confirming that circulating endothelial progenitor cells (EPCs) are involved inRetinopathy of prematurity (ROP) is the primary cause of visual impairment in preterm infants. There are available data confirming that circulating endothelial progenitor cells (EPCs) are involved in forming the growing network of blood vessels in the developing retina. In this study we sought to explore potential relationship between concentration of circulating bone marrow-derived EPCs and development of ROP in prospective study. The study groups consisted of 90 preterm (23-36 weeks of gestational age), and 52 full-term control infants. EPCs were analyzed in cord blood (CB) and subsequently in peripheral blood (PB) in second and sixth week since delivery. The incidence and stage of ROP was prospectively documented in the preterm infants. EPC concentration in CB was considerably higher in the preterm infants developing ROP. In the preterm infants a noticeable decrease in PB EPC concentration within six weeks of the follow up was found, whereas in full-term infants EPC concentration was maintained at invariable level. Of note, in the sixth week since delivery, EPC concentration in preterm infants with ROP was lower compared to preterm infants without ROP. Increase in CB EPC concentration in preterm infants, including those developing ROP, indicates that the circulating EPC cells contribute to the process of blood vessel formation, and their number in CB reflects the degree of prematurity. Impaired blood vessel formation within retina in the course of ROP may result from decrease in circulating EPC number observed at the sixth week since delivery.

• [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.

• [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.

• 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.

• 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.

• [Stem cells in adult retina--current state of research, future therapeutic prospects]

  Authors: Anna Machalińska, Ewa K Zuba-Surma

  Klinika oczna. 01/2009; 111(7-9):253-7.

  The latest research reports revealed the presence of stem/progenitor cells located in different regions of matured eye. They are able to differentiate into retinal pigment epithelium cells as well asThe latest research reports revealed the presence of stem/progenitor cells located in different regions of matured eye. They are able to differentiate into retinal pigment epithelium cells as well as neural structure of retina. These cells were identified in neurosensory retina, pigment epithelium and within cilliary body and iris epithelium. Moreover, it has been proved that Muller glia possess the potential of differentiation into retinal cells. These findings indicate the presence of potential mechanisms enabling retinal cell repopulation and retinal tissue regeneration. In the present work, the recent reports documenting the presence of different stem cell populations in eye have been reviewed, particularly focusing on recently identified very small embryonic-like stem cells (VSEL-SCs). The potential clinical applications of the residing stem cells and limitations of such therapeutic strategies have been also discussed.

• [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.

• [Role of complement system in the pathogenesis of AMD].

  Authors: Anna Machalińska, Danuta Karczewicz

  Klinika oczna. 01/2009; 111(10-12):384-7.

  Age related macular degeneration (AMD), is the leading cause of blindness in individuals over age 50 years old. The pathogenesis of AMD is still not well understood with both genetic andAge related macular degeneration (AMD), is the leading cause of blindness in individuals over age 50 years old. The pathogenesis of AMD is still not well understood with both genetic and environmental factors known to influence susceptibility to this condition. Data accumulated in the last decade implicate the chronic inflammatory processes as playing an important role in the progression of AMD. According to the recent findings, complement system is suggested to be a triggering point of the initiation of pathologic inflammatory response in the development and clinical course of AMD.

• [Stem cells--new perspectives in the treatment of retinal disorders]

  Authors: Anna Machalińska, Danuta Karczewicz, Bogusław Machaliński

  Klinika oczna. 02/2006; 108(10-12):471-4.

  The progress of clinical science since a few last years indicates the possibility that stem cells could be used in the treatment of retinal disorders. The bone marrow seems to be the most availableThe progress of clinical science since a few last years indicates the possibility that stem cells could be used in the treatment of retinal disorders. The bone marrow seems to be the most available source of the stem cells for such purposes. This review describes the latest attempts to use the stem cells, isolated from the bone marrow, in the treatment of retinal injuries. The research performed in animal models, so far gives hope to use that innovatory strategy in humans.

• Hypoglycemic potency of novel trivalent chromium in hyperglycemic insulin-deficient rats.

  Authors: Bogusław Machaliński, Mieczysław Walczak, Anhelli Syrenicz, Anna Machalińska, Katarzyna Grymuła, Iwona Stecewicz, Barbara Wiszniewska, Elzbieta Dabkowska

  Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 02/2006; 20(1):33-9.

  Two sources of chromium III, "chromium 454" and "chromium picolinate," were tested in insulin-deficient Streptozocin-treated diabetic rats. This model was selected in order to evaluate theTwo sources of chromium III, "chromium 454" and "chromium picolinate," were tested in insulin-deficient Streptozocin-treated diabetic rats. This model was selected in order to evaluate the possibility of any hypoglycemic potency of chromium in a relative absence of blood insulin concentration. Three weeks of the treatment with CRC454 and CrP resulted in a 38% and 11% reduction of blood glucose levels, respectively. Body weight gains were equally improved by both treatments. Blood levels of CK, ALT and AST were significantly reduced by CRC454 and CrP. These results might suggest that any hypoglycemic effect of trivalent chromium under insulin-deficient conditions could be largely dependent upon the type of chromium agent and associated characteristics such as solubility and bioavalibility. In contrast, improvement of body weight gains and blood levels of CK, AST and ALT seems to be less dependent on the type of chromium compound under these experimental conditions. In conclusion, CRC454 showed significant reduction of hyperglycemia under insulin-deficient conditions.

• Hypoglycemic potency of novel trivalent chromium in hyperglycemic insulin-deficient rats

  Authors: Bogusław Machaliński, Mieczysław Walczak, Anhelli Syrenicz, Anna Machalińska, Katarzyna Grymuła, Iwona Stecewicz, Barbara Wiszniewska, Elżbieta Dąbkowska

  Journal of Trace Elements in Medicine and Biology.

  Two sources of chromium III, “chromium 454” and “chromium picolinate,” were tested in insulin-deficient Streptozocin-treated diabetic rats. This model was selected in order to evaluate theTwo sources of chromium III, “chromium 454” and “chromium picolinate,” were tested in insulin-deficient Streptozocin-treated diabetic rats. This model was selected in order to evaluate the possibility of any hypoglycemic potency of chromium in a relative absence of blood insulin concentration.Three weeks of the treatment with CRC454 and CrP resulted in a 38% and 11% reduction of blood glucose levels, respectively. Body weight gains were equally improved by both treatments. Blood levels of CK, ALT and AST were significantly reduced by CRC454 and CrP. These results might suggest that any hypoglycemic effect of trivalent chromium under insulin-deficient conditions could be largely dependent upon the type of chromium agent and associated characteristics such as solubility and bioavalibility. In contrast, improvement of body weight gains and blood levels of CK, AST and ALT seems to be less dependent on the type of chromium compound under these experimental conditions. In conclusion, CRC454 showed significant reduction of hyperglycemia under insulin-deficient conditions.