Mechanism Of Calcification Research Articles

Bevacizumab-induced tumor calcifications can be elicited in glioblastoma microspheroid culture and represent massive calcium accumulation death (MCAD) of tumor endothelial cells

AbstractBähr and colleagues reported that 22 of 36 glioblastoma patients treated with bevacizumab showed tumor calcifications on 8 week post therapy follow up with MRI. Early tumor calcification strongly predicted for response, time to progression, and overall survival. The authors didn’t understand the mechanism, but speculated that it was vascular in nature. At the 13th International Anti-Angiogenic Symposium (2011), we presented our discovery of the phenomenon of massive calcium accumulation death, wherein MCAD occurred in endothelial cells (tumor, circulating, and HUVEC), in response to VEGF depletion by bevacizumab and other putative anti-angiogenic agents, but not in response to non-specific cytotoxins. In subsequent work, we have documented marked MCAD to occur in primary microcluster cultures from 6 fresh human glioblastoma biopsies, following 96 hours of VEGF depletion in vitro by bevacizumab. The presence and degree of MCAD is strikingly dependent on the type of serum in the culture medium (RPMI-1640 + 25% serum) -- typically most striking in (very low VEGF) fetal calf serum, but inhibited (often) or enhanced (rarely) by 25% human serum from different patients or normal donors containing variable quantities of VEGF. There was not a linear relationship between VEGF concentration and MCAD inhibition (or enhancement), suggesting that other pro-angiogenic (or anti-angiogenic) serum factors may play a role. In epithelial metastatic tumors, circulating peripheral blood endothelial cells may be easily tested, using our methods, and the serum inhibition (or, rarely, enhancement) is faithfully reproduced on circulating endothelial cells, in comparison with the tumor cluster-associated endothelial cells. We propose MCAD as the mechanism of glioblastoma calcification following bevacizumab and further propose that testing tumor microclusters and/or circulating endothelial cells, in the presence of autologous serum, could be a useful predictive biomarker and research tool.

Confocal laser scanning microscopy in study of bone calcification

Bone regeneration in mandible and maxillae after extraction of teeth or tumor resection and the use of rough surface implants in bone induction must be investigated to elucidate the mechanism of calcification. The calcified tissues are subjected to chemical decalcification or physical grinding to observe their microscopic features with light microscopy and transmission electron microscopy where the microscopic tissue morphology is significantly altered. We investigated the usefulness of confocal laser scanning microscopy (CLSM) for this purpose. After staggering the time of administration of calcein and alizarin red to experimental rats and dogs, rat alveolar bone and dog femur grafted with coral as scaffold or dental implants were observed with CLSM. In rat alveolar bone, the calcification of newly-formed bone and net-like canaliculi was observed at the mesial bone from the roots progressed at the rate of 15μm/day. In dog femur grafted with coral, newly-formed bones along the space of coral were observed in an orderly manner. In dog femur with dental implants, after 8 weeks, newly-formed bone proceeded along the rough surface of the implants. CLSM produced high-magnification images of newly-formed bone and thin sections were not needed.

RETRACTED: The effect of alendronate on the expression of osteopontin and osteoprotegerin in calcified aortic tissue of the rat

Vascular calcification is a pathobiological process which leads to high morbidity and mortality in cardiovascular disease. The association between vascular calcification and osteoporosis has been reported widely, and there are close relationships among vascular calcification, related cardiovascular disease and osteoporosis, but the biochemical mechanism of vascular calcification is presently unclear. For exploring the possible mechanism of artery calcification we established aorta calcification in an animal model with vitamin D(3) and warfarin and tested the effect of alendronate on the expression of osteopontin and osteoprotegerin in calcified aorta tissue of the rat through measuring gene and protein expression of osteopontin and osteoprotegerin respectively. The results indicated compared with control group, the aortic calcium content of calcification group was obviously increased, osteopontin mRNA and osteoprotegerin mRNA were significantly reduced, and osteoprotegerin and osteopontin protein expressions were reduced. Compared with calcification group, the aortic calcium content of alendronate group was obviously reduced, osteopontin mRNA and osteoprotegerin mRNA were significantly increased, and osteopontin and osteoprotegerin protein expression were increased. We conclude that artery calcification may reduce the expression of osteopontin and osteoprotegerin. Alendronate may inhibit rat aorta calcification by up-regulating osteopontin and osteoprotegerin expression.

Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis and survival.

Patients with chronic kidney disease (CKD) have a high prevalence of vascular calcification, and cardiovascular disease is the leading cause of death in this population. However, the molecular mechanisms of vascular calcification, which are multifactorial, cell-mediated and dynamic, are not yet fully understood. We need to address ways to improve outcomes in CKD patients, both in terms of vascular calcification and cardiovascular morbidity and mortality—and to these ends, we investigate the role of magnesium. Magnesium’s role in the pathogenesis of vascular calcification has not been extensively studied. Nonetheless, several in vitro and animal studies point towards a protective role of magnesium through multiple molecular mechanisms. Magnesium is a natural calcium antagonist and both human and animal studies have shown that low circulating magnesium levels are associated with vascular calcification. Clinical evidence from observational studies of dialysis patients has shown that low-magnesium levels occur concurrently with mitral annular calcification, peripheral arterial calcification and increased carotid intima–media thickness. Few interventional studies have been performed. Two interventional studies suggest that there may be benefits such as retardation of arterial calcification and/or reductions in carotid intima–media thickness in response to magnesium supplementation in CKD patients, though both studies have limitations. Finally, observational studies have shown that low serum magnesium may be an independent risk factor for premature death in CKD patients, and patients with mildly elevated serum magnesium levels could have a survival advantage over those with lower magnesium levels.

Kidney and bone update : the 5-year history and future of CKD-MBD. Bisphosphonates treatment for chronic kidney disease-mineral and bone disorder

Recently, much of the attention given to bone-mineral disorder as the prognostic factor for mortality has focused on their links to chronic-kidney disease. High-frequency severe atherosclerosis/calcinosis is observed in chronic dialysis, which leads to cardiovascular events. Recent progress in basic research has revealed certain similarities between processes of bone calcification and calcifications of vascular tissues which contribute to several cardiovascular diseases. However, the effective treatment for suppressing the progression of vascular calcification has not been established. Here we review the mechanism of vascular calcification and present our findings that a bisphosphonate is useful in prevention of vascular calcification in chronic renal failure.

3．加齢による動脈硬化の分子機序

3．加齢による動脈硬化の分子機序

The mechanism of vascular calcification – a systematic review

SummaryCalcification of vessels reduces their elasticity, affecting hemodynamic parameters of the cardiovascular system. The development of arterial hypertension, cardiac hypertrophy, ischemic heart disease or peripheral arterial disease significantly increases mortality in patients over 60 years of age. Stage of advancement and the extent of accumulation of calcium deposits in vessel walls are key risk factors of ischemic events.Vascular calcification is an active and complex process that involves numerous mechanisms responsible for calcium depositions in arterial walls. They lead to increase in arterial stiffness and in pulse wave velocity, which in turn increases cardiovascular disease morbidity and mortality.In-depth study and thorough understanding of vascular calcification mechanisms may be crucial for establishing an effective vasculoprotective therapy.The aim of this study was to present a comprehensive survey of current state-of-the-art research into the impact of metabolic and hormonal disorders on development of vascular calcification.Due to strong resemblance to the processes occurring in bone tissue, drugs used for osteoporosis treatment (calcitriol, estradiol, bisphosphonates) may interfere with the processes occurring in the vessel wall. On the other hand, drugs used to treat cardiovascular problems (statins, angiotensin convertase inhibitors, warfarin, heparins) may have an effect on bone tissue metabolism. Efforts to optimally control calcium and phosphate concentrations are also beneficial for patients with end-stage renal disease, for whom vessel calcification remains a major problem.

Unicommissural aortic valves: gross, histological, and immunohistochemical analysis of 52 cases (1978-2008)

Unicommissural aortic valves (UAVs) are rare anomalies in which adjacent cusps of two commissures are congenitally fused. Currently, features of UAVs are poorly characterized. Fifty-two surgical and autopsy cases of UAV at Mayo Clinic were evaluated for various clinicopathologic features. Histology and immunohistochemistry (IHC) were used in 30 UAVs to identify biomarkers important to developing aortic stenosis. In 52 UAV patients (58% were male, 42% were female), their ages ranged from 18 weeks' gestation to 80 years (mean, 28 years). Functional status was pure stenosis in 20, pure regurgitation in 9, combined in 22, and normal in 1. Common additional cardiovascular disorders included left ventricular hypertrophy (56%) and ascending aortopathies (42%). The position of the true commissure was determined in 30 UAVs and was left posterior in 73%. Gross calcification increased exponentially with age, starting as early as 16 years. Microscopically, the values of the 3 youngest patients showed dysplasia. Other UAVs exhibited fibrous thickening (93%), ventricular pads (89%), aortic pads (81%), and thickened spongy layer (74%). Macrophages were the most common leukocyte by IHC. Bone morphogenetic protein-2 was positive in 27 IHC cases; osteopontin was positive in 15, and matrix metalloproteinase (MMP) 2, MMP-9, and MMP-14 were positive in 1, 6, and 4 cases, respectively. The functional status of UAVs typically involves stenosis but can vary in type and degree or rarely be normal. In early stenosis (<16 years), the pathology is primarily fibrosis with minimal calcification. UAVs show more calcification compared with age-matched bicuspid or tricuspid aortic valves. The molecular mechanisms of calcification and fibrosis in UAVs remain incompletely understood.

Reviewing -Gal in valve immunology

Calcification of bioprosthetic heart valves is an unsolved problem ever since. Lim et al. [1] recently made another attempt to improve tissue performance by applying the novel fixation agent genipin. Numerous efforts of chemical tissue pretreatment have been tested, but up to now, the longevity of biovalves has not substantially increased, especially not in young recipients. Our group has shown that the implantation of biovalves causes an increase in anti-Gal immunoglobulin M and immunoglobulin G (IgG) titers in patients [2, 3]. Thus, we suggested a mechanism of chronic xenograft rejection and consecutive calcification via that anti-Gal response. The α-Gal barrier is known to prevent xenotransplantation from suitable animals to humans, because humans and old world monkeys are the sole mammals which produce anti-Gal antibodies in high titers and lack the α-Gal epitope [4]. Since recently, biovalve researchers perceive the problem of α-Gal antigenicity in glutaraldehyde-fixed biovalves, and α-Gal knockout pigs are proposed as a possible source for valve tissue [5, 6]. Lim et al. [1] delivered a concise report on the use of the cross-linking agent genipin in the pretreatment of bovine pericardium and evaluated calcification in a rabbit intramuscular transplantation model. They proved the superiority of genipin over glutaraldehyde to prevent tissue calcification in a clear sequence of experiments. However, their interpretation of the α-Gal barrier in their setup is disconcerting. They implanted bovine tissue into a rabbit muscle and measured anti-Gal IgG antibodies in plasma before, 12 and 60 days after implantation. Genipin-treated tissue recipients showed significantly lower anti-Gal IgG titers than glutaraldehyde-treated tissue recipients. Furthermore, they showed that decellularization of tissue before implantation abolished this titer increase. But rabbits do not have any anti-α-Gal antibodies, as they express the α-Gal epitope themselves; at least according to the present opinion. How are these results possible then? The authors do not give a clear statement; they indicate an explanation by not correctly citing Macher and Galili [4], saying ‘the differences in the fine specificity of natural anti-Gal in various species may cause the multiple B-cell clones to produce anti-Gal antibodies which have specificities that differ slightly from each other, and thus recognize various facets of the a-Gal epitope in its three-dimensional form’. But Macher and Galili never mention ‘various species’, they merely speak of anti-Gal varieties among individuals. Do the authors suggest differing α-Gal epitopes among different species? This is unlikely, as the sequence homology of α1,3GT is very high among a wide range of species [4]. If uniform Gal epitopes are assumed, one would expect autoimmunologic affection in animals with elevated anti-Gal titers; did the transplanted animals show any signs of systemic inflammation? Most of the researchers who measure anti-Gal antibodies use self-established ELISAs with internal or no standards. Such ELISAs require extensive titration steps to yield a reliable technique that is suitable for publication. Reevaluation and verification of the results of Lim et al. should be considered.

Bone and calcium update; diagnosis and therapy of bone metabolism disease update. Molecular mechanism in cardiac valve calcification

When cardiac valve stenosis is accompanied by calcification, symptoms and prognosis become much worse and may cause sudden cardiac death. The prevalence of this disease has increased with the rapidly aging in Japanese society. It has recently been revealed that several genes which relate to physiological ossification and calcification play important roles in this process. To find a suitable target for medical treatment, the molecular mechanism for calcification of cardiac valves should be elucidated in detail. In this review, we summarize the current knowledge on the pathology and molecular mechanism for ectopic calcification of the cardiac valve.

Abstract 17354: Aortic Stenosis in Women vs. Men: Differential Severity to Calcification Load Relationship

Introduction: Aortic Stenosis (AS) is a common valve disease of the adult, caused by calcification of aortic cusps. The relationship between cusp calcification and severity of AS has been established mostly in men and it is unclear whether the calcification process and its relation to AS severity is similar in women Hypothesis: We hypothesized that the physiologic relation between aortic valve calcification (AVC) load and AS severity is different in men and women and that lower calcification loads may lead to severe AS in women Methods: We prospectively performed high resolution computed tomography (CT) without contrast in 679 patients with AS (Aortic valve area (AVA) &lt;2cm 2 , Mean gradient ≥10 mmHg) at two academic centers (Rochester, MN; Paris, France) to measure AVC scores and compare these to the hemodynamic obstruction measured by Echo-Doppler. Results: Women vs. men were older (76±11 vs 74±11, p&lt;0.0001) with slightly higher ejection fraction (62±12 vs 59±13, p=0.001) but AS severity was similar (AVA/body surface area 0.55±0.2 vs 0.56±0.2 cm 2 /m 2 ; Peak velocity 4±1 vs 3.9±1 m/s; Mean gradient 41±21 vs 38±18 mmHg, all p≥0.1). Yet, AVC load was lower in women vs men, score absolute or normalized for LVOT area (551±383 vs 626±399 all p&lt;0.0001). For those with severe AS (Mean gradient &gt;40 mmHg), AVC scores were 2433±1412 in women vs 3805±1587 in men. Multivariate analysis adjusting for age, BSA, LVOT area and mean gradient, confirmed that severe AS was achieved with lower AVC load in women (all p&lt;0.0001). Conclusions: In this large multicenter AS population, women reached similar AS severity than males for lower calcium loads, even after adjustment for lower body and LVOT size. Hence the relation between valvular calcification process and severity of AS differs in women vs. men. Thus, future studies are needed to determine the differential mechanism of aortic calcification in men and women and diagnostic consideration must be given to gender in the interpretation of AS severity by AVC load.

Calcifying coral abundance near low-pH springs: implications for future ocean acidification

Rising atmospheric CO2 and its equilibration with surface ocean seawater is lowering both the pH and carbonate saturation state (Ω) of the oceans. Numerous calcifying organisms, including reef-building corals, may be severely impacted by declining aragonite and calcite saturation, but the fate of coral reef ecosystems in response to ocean acidification remains largely unexplored. Naturally low saturation (Ω ~ 0.5) low pH (6.70–7.30) groundwater has been discharging for millennia at localized submarine springs (called “ojos”) at Puerto Morelos, México near the Mesoamerican Reef. This ecosystem provides insights into potential long term responses of coral ecosystems to low saturation conditions. In-situ chemical and biological data indicate that both coral species richness and coral colony size decline with increasing proximity to low-saturation, low-pH waters at the ojo centers. Only three scleractinian coral species (Porites astreoides, Porites divaricata, and Siderastrea radians) occur in undersaturated waters at all ojos examined. Because these three species are rarely major contributors to Caribbean reef framework, these data may indicate that today’s more complex frame-building species may be replaced by smaller, possibly patchy, colonies of only a few species along the Mesoamerican Barrier Reef. The growth of these scleractinian coral species at undersaturated conditions illustrates that the response to ocean acidification is likely to vary across species and environments; thus, our data emphasize the need to better understand the mechanisms of calcification to more accurately predict future impacts of ocean acidification.

Expressions of Runx2 and osteocalcin in the calcified heart valve

Objective To study mechanism for valve calcification in rheumatic and degenerative heart diseases.Methods In patients with rheumatic and degenerative diseases,We examined calcified human heart valves which were replaced at surgery ( n =10).The control group was obtained from four removed hearts suffered from dilated cardiomyopathy.Results Von Kossa staining was used to assess the extent of mineralization and confirm the presence of calcification in both calcified groups.Immunohistochemistry verified the presentation of Runx2 in valve interstitial cells and osteocalcin in the endothecium of the valve.Reverse transcription-polymerase chain reaction (RT-PCR) revealed the increased mRNA levels of Runx2 (0.297 ±0.154 vs.0.287 ±0.172) and osteocalcin (0.178 ±0.087 vs.190 ±0.095).Conclusion These findings support the concept that there is the similar mechanism of calcification in rheumatic and degenerative diseases.Meanwhile,Runx2 is a potential biological marker in the pathogenesis. Key words: Heart valves; Runx2 ; Osteocalcin; Calcification

Calcification mechanism in freshwater mussels: potential targets for cadmium

In freshwater mussels (Bivalvia, Unionoida), the uptake, transport, and metabolism of calcium is a highly ordered and regulated mechanism. Large amounts of calcium ion is required for the construction of the bivalve exoskeleton, the shell, yet itis additionally used in many physiological functions such as cellular signaling, acid–base regulation, and muscular contraction. Due to the relatively low Ca2+ concentrations in most freshwater environments, calcium uptake in unionids is mainly an active transport. The actively pumped calcium has to be transitorily stored inside the body for the main calcification events: shell construction of adults and larvae, latter of which are brooded in female gills. In addition, calcium stores have an active role in the acid–base regulation of internal fluids. The transport of calcium toward and from the transitory stores by diffusion or transcellular processes is highly regulated. Against this background, any detectable changes in this sensible physiological mechanism that are caused by external factors, such as pollutants, may be used to evaluate the toxicological effects on these animals. Cadmium, as a calcium ion competitor, disrupts this mechanism at several levels. Thus, cadmium uptake, transport, storage, and regulation greatly affect the main biomineralization events, and might lead to unstructured brittle shells and a decrease or even halt in recruitment.

Vascular Calcification in Patients With Chronic Kidney Disease

Vascular calcification is very prevalent in patients with chronic kidney disease (CKD). In addition to having more traditional cardiovascular (CV) risk factors, CKD patients also have a number of non-traditional CV risk factors that may play a prominent role in the pathogenesis of vascular calcification. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of vascular calcification in the presence of calcium (Ca) and phosphorus (P) deposition due to abnormal bone metabolism and impaired renal excretion. Vascular calcification causes increased arterial stiffness, left ventricular hypertrophy, decreased coronary artery perfusion, myocardial ischemia, and increased cardiovascular morbidity and mortality. Although current treatment strategies focus on correcting abnormal Ca, P, parathyroid hormone, or vitamin D levels in CKD, a better understanding of the mechanisms of abnormal tissue calcification may lead to the development of new therapeutic agents that are capable of reducing vascular calcification and improving the CV outcome of CKD patients. This review article summarizes the following: (i) the pathophysiological mechanism responsible for vascular calcification; (ii) the methods of detecting vascular calcification in CKD patients; and (iii) the treatment of vascular calcification in CKD patients.

Severe calcification of the aorta (porcelain aorta) associated with sarcoidosis in a pediatric heart transplant recipient

We report a unique case of severe calcification of the aorta, bilateral coronary ostial stenoses and calcification of the mitral valve and left ventricle due to sarcoidosis. The patient underwent neonatal orthotopic heart transplantation secondary to hypoplastic left heart syndrome and developed hypercalcemia with other features of sarcoidosis at 10 yr of age. The mechanism for severe extra-renal calcification localized to the allograft is poorly understood, but may involve discordant local immune modulation and/or calcification-regulation between graft and host tissues.

High-density lipoproteins (HDL) are present in stenotic aortic valves and may interfere with the mechanisms of valvular calcification

ObjectiveTo determine whether differences exist in valvular high density lipoprotein (HDL) content between non-stenotic and stenotic aortic valves, and whether HDL could retard valvular calcification locally. MethodsStenotic aortic valves were obtained from valve replacement surgery and non-stenotic control valves from cardiac transplantations or at autopsy. The valvular localization and concentration of apolipoproteinA-I (apoA-I) were analyzed by immunohistochemistry and ELISA. The effects of HDL on the secretion of calcifying mediators and proinflammatory cytokines by cultured aortic valve myofibroblasts were assessed by ELISA and real-time PCR. ResultsThe concentration of apoA-I was higher in control than in stenotic valves (p<0.05). ApoA-I surrounded the calcific deposits in stenotic valves, co-localizing with apoB, apoE, and osteoprotegerin (OPG). Incubation of cultured valve myofibroblasts with HDL increased their secretion of OPG (p<0.001). Furthermore, incubation of myofibroblasts with HDL led to decreased mRNA expression of tumor necrosis factor alpha (TNF-α) (p<0.05). ConclusionsThe amount of valvular HDL is reduced in aortic valve stenosis. HDL both induces the secretion of OPG and reduces the expression of TNF-αin vitro. Since OPG is known to inhibit and TNF-α to promote aortic valve calcification, HDL may have an anti-calcifying effect in human aortic valves.

Initiation and progression of ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy)

IntroductionOssification of the posterior longitudinal ligament (OPLL) is a significantly critical pathology that can eventually cause serious myelopathy. Ossification commences in the vertebral posterior longitudinal ligaments, and intensifies and spreads with the progression of the disease, resulting in osseous projections and compression of the spinal cord. However, the paucity of histological studies the underlying mechanisms of calcification and ossification processes remain obscure. The pathological process could be simulated in the ossifying process of the ligament in mutant spinal hyperostotic mouse (twy/twy). The aim of this study is to observe that enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of the posterior longitudinal ligament of twy/twy mice.Materials and methodsThe mutant twy/twy mice (6 to 22-week-old) were used in the present study. The vertebral column was analyzed histologically and immunohistochemically.ResultsWe observed that the enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilaginous tissues participated in the initiation of ossification of posterior longitudinal ligament of twy/twy mice. In this regards, the cells of the protruded hyperplastic annulus fibrosus invaded the longitudinal ligaments and induced neovascularization and metaplasia of primitive mesenchymal cells to osteoblasts in the spinal ligaments of twy/twy mice.ConclusionSince genetic mechanisms could play a role in human OPLL, the age-related enlargement of the nucleus pulposus in the twy/twy mouse may primarily occur as a result of overproduction of mucopolysaccharide matrix material induced by certain genetic abnormalities.Electronic supplementary materialThe online version of this article (doi:10.1007/s00586-011-1971-7) contains supplementary material, which is available to authorized users.

MiR-125b Regulates Calcification of Vascular Smooth Muscle Cells

Vascular calcification is a prominent feature of atherosclerosis and is closely linked to osteoporosis. Cellular differentiation is regulated by various microRNAs (miRs), including miR-125b, which is known to be involved in osteoblast differentiation. However, no specific miR has been defined that modulates vascular calcification. Herein, we assessed the impact of miR-125b in osteogenic transformation of vascular smooth muscle cells. Osteogenic transdifferentiation of human coronary artery smooth muscle cells was induced by osteogenic medium and enhanced the formation of mineralized matrix, resulting in a significantly higher mineral deposition after 21 days. Increased expression of miR-125b was time-dependent in human coronary artery smooth muscle cells and diminished during osteogenic transdifferentiation. At day 21, miR-125b was significantly reduced (-42%) compared with that in the untreated control. The expression of miR-processing enzymes, RNase III endonucleases DICER1 and DROSHA, was also decreased. Furthermore, inhibition of endogenous miR-125b promoted osteogenic transdifferentiation, as measured by increased alkaline phosphatase activity and matrix mineralization. Expression analysis revealed the osteoblast transcription factor SP7 (osterix) as a target of miR-125b. In vivo, miR-125b was decreased in calcified aortas of apolipoprotein E knockout mice. In conclusion, our results suggest that miR-125b is involved in vascular calcification in vitro and in vivo, at least partially by targeting SP7. Evaluating the role of miRs in arterial calcification in vivo may have important therapeutic implications.

Experimental Investigation on Mechanism of Hydrophilic Acrylic Intraocular Lens Calcification

To construct a model simulating intraocular lens (IOL) opacification attributable to the formation of calcium phosphate deposits and to investigate the kinetics of deposit formation. Prospective laboratory investigation. Department of Ophthalmology, Medical School and Department of Chemical Engineering, Laboratory of Inorganic and Analytical Chemistry, University of Patras, Greece. Three hydrophilic acrylic IOLs (26% water content) were placed inside a 10-mL double-walled thermostated reactor simulating the anterior chamber. Simulated aqueous humor was injected continuously into the reactor using a pump with variable speed. The observation of IOLs was carried out in situ daily by optical microscopy. Scanning electron microscopy and energy-dispersive radiographic spectroscopy were used for the identification of the morphologic features and the composition of the deposits. The lenses were removed and inspected 5, 9, and 12 months after the initiation of the experiment. Investigation showed deposits of calcium phosphate crystallites in the interior of opacified IOLs. However, these deposits were not observed on the surface of the IOLs. In agreement with earlier reports by our group and in the literature, IOL opacification is the result of calcification. It is suggested that the surface hydroxyl groups of the polyacrylic polymeric components of the IOLs are capable of inducing surface nucleation and crystal growth of calcium phosphates. However, most important is the finding that the calcification of IOLs is initiated from their interior through the development of sufficiently high local supersaturation, realized through the diffusion of calcium and phosphate ions.