Biomedical subjects

Andreas Reichenbach

Publications and source records attributed to Andreas Reichenbach.

At least 55 records · Page 3Linked to original sources

PubMed2005

Identification of P2Y receptor subtypes in human muller glial cells by physiology, single cell RT-PCR, and immunohistochemistry.

PURPOSE: Retinal Müller glial cells are known to express metabotropic P2Y receptors. The present study was conducted to identify certain subtypes of P2Y receptors in human Müller cells. METHODS: The patch-clamp technique was used to measure increases of Ca(2+)-dependent K+ currents mediated by the activation of P2Y receptors in freshly isolated human Müller cells. Several P2 agonists were used. Subsequently, the cells were harvested into the patch pipette and a single cell RT-PCR was performed. Moreover, retinal tissue from organ donors was used for immunohistochemistry. RESULTS: The electrophysiological data were consistent with the expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes. RT-PCR revealed that mRNA for all these subtypes was present in Müller cells. However, the incidence of P2Y2 receptor mRNA was significantly lower than that of the other subtypes. Immunoreactivity for all four subtypes was found in retinal tissue, partly colocalized with immunoreactivity for vimentin. CONCLUSIONS: The presented data obtained by different techniques revealed that human Müller cells express P2Y1, P2Y2, P2Y4, and P2Y6 receptors. The specific roles of these receptor subtypes in retinal physiology and/or pathophysiology remain to be investigated in future studies.

Fluorescent Antibody Technique, Indirect↗

PubMed2004

Glutamate-evoked alterations of glial and neuronal cell morphology in the guinea pig retina.

Neuronal activity is accompanied by transmembranous ion fluxes that cause cell volume changes. In whole mounts of the guinea pig retina, application of glutamate resulted in fast swelling of neuronal cell bodies in the ganglion cell layer (GCL) and the inner nuclear layer (INL) (by approximately 40%) and a concomitant decrease of the thickness of glial cell processes in the inner plexiform layer (IPL) (by approximately 40%) that was accompanied by an elongation of the glial cells, by a thickening of the whole retinal tissue, and by a shrinkage of the extracellular space (by approximately 18%). The half-maximal effect of glutamate was observed at approximately 250 mum, after approximately 4 min. The swelling was caused predominantly by AMPA-kainate receptor-mediated influx of Na+ into retinal neurons. Similar but transient morphological alterations were induced by high K+ and dopamine, which caused release of endogenous glutamate and subsequent activation of AMPA-kainate receptors. Apparently, retinal glutamatergic transmission is accompanied by neuronal cell swelling that causes compensatory morphological alterations of glial cells. The effect of dopamine was elicitable only during light adaptation but not in the dark, and glutamate and high K+ induced strong ereffects in the dark than in the light. This suggests that not only the endogenous release of dopamine but also the responsiveness of glutamatergic neurons to dopamine is regulated by light-dark adaptation. Similar morphological alterations (neuronal swelling and decreased glial process thickness) were observed in whole mounts isolated immediately after experimental retinal ischemia, suggesting an involvement of AMPA-kainate receptor activation in putative neurotoxic cell swelling in the postischemic retina.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2004

PEDF derived from glial Müller cells: a possible regulator of retinal angiogenesis.

A precise balance between stimulators and inhibitors of angiogenesis, such as vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), respectively, is essential for angiogenic homeostasis in ocular tissues. Retinal hypoxia is accompanied by some pathological conditions that may promote intraocular neovascularization. Here we demonstrate that retinal glial (Müller) cells express and release pigment epithelium-derived factor (PEDF). Decreasing oxygen concentrations cause strong attenuation of PEDF release resulting in enhanced VEGF/PEDF ratios. Exposure of Müller cells to VEGF suppressed PEDF release in a dose-dependent manner. This may represent a novel mechanism of ocular angiogenic homeostasis sufficient in the control of PEDF levels during normoxia or mild hypoxia but supplemented by other (hitherto unknown) mechanisms in cases of strong hypoxia. In spite of the enhanced VEGF/PEDF ratios resulting from hypoxia, conditioned media of Müller cells failed to stimulate additional proliferation of retinal endothelial cells. These findings suggest that in the ischemic retina, Müller cells generate a permissive condition for angiogenesis by secreting more VEGF and less PEDF, but the onset of retinal endothelial cell proliferation requires another triggering signal that remains to be identified.

Animals↗

PubMed2004

Neuropeptide Y-evoked proliferation of retinal glial (Muller) cells.

BACKGROUND: Glial cells in human retinas and in fibrocellular membranes from patients with proliferative vitreoretinopathy (PVR) have been described to upregulate their expression of Y1 receptors for neuropeptide Y (NPY) (Soler et al.: Glia 39:320, 2002). However, it is unknown whether Y1 receptor activation causes proliferation of retinal glial cells. We investigated whether NPY exerts a proliferation-stimulating effect on retinal glial cells, and compared the NPY-evoked signaling with the signaling of purinergic P2Y receptors. METHODS: Proliferation assays using bromodeoxyuridine were carried out on primarily cultured Muller glial cells of the guinea pig, in the absence and presence of blockers of Y1 receptors, of receptor tyrosine kinases (RTKs), of mitogen-activated protein kinases (MAPKs) and of phosphatidylinositol-3 kinase (PI3K). RESULTS: NPY exerted a biphasic effect on Muller cell proliferation. At low concentrations (0.1 ng/ml and 1 ng/ml) it decreased the proliferation rate of the cells, while at higher concentration (100 ng/ml) it increased Muller cell proliferation. The NPY-evoked proliferation was mediated by Y1 receptor stimulation and by activation of the p44/p42 MAPKs and partially of the p38 MAPK. Moreover, Y1 receptor-induced activation of PI3K as well as transactivations of the platelet-derived and the epidermal growth factor RTKs were necessary for full mitogenic effect of NPY. Y1 and P2Y receptors share partially common signal transduction pathways in Muller cells. CONCLUSION: It is suggested that NPY may be involved in stimulation of retinal glial cell proliferation during PVR when it is released at higher amounts into the injured retina.

Adenosine Triphosphate↗

PubMed2004

Switch of K+ buffering conditions in rabbit retinal Müller glial cells during postnatal development.

Although spatial buffering of excess extracellular K+ by K+ channels is a main function of retinal glial (Müller) cells, there are severe limitations to long distance K+-spatial buffering that have been predicted for (immature) glial cells: (i) a lack of inwardly rectifying K+ (Kir) channels [Glia 21(1997) 46]; and (ii) high internal resistance of outgrowing (cable like) processes [W. Rall, Handbook of Physiology, Section 1, vol. 1, Part 1, American Physiological Society, Bethesda, 1977, pp. 39-97]. In order to determine if changes in developing Müller cells improve or worsen their capability of carrying K+ spatial buffering currents, we compared the whole-cell currents of acutely isolated Müller cells at 5, 11 and 28 postnatal days of rabbits. Both K+-spatial buffer limitations described above were found in early postnatal stage (5 days), however, the cells overcome these limitations shortly after 11 days. During the period of 11-28 days, rabbit Müller cells simultaneously increase stalk axial conductance and express Kir channels. Both processes take place during the critical stage of retinal maturation, and should dramatically improve "cable" K+-spatial buffering.

Animals↗

PubMed2004

Angiogenesis-related factors derived from retinal glial (Müller) cells in hypoxia.

Retinal glial (Müller) cells may play a major role in vascular eye diseases as they secrete vascular endothelial growth factor (VEGF), a hypoxia-induced angiogenic cytokine. They also release significant amounts of the anti-angiogenic factors, transforming growth factor (TGF)-beta2, pigment epithelium derived factor (PEDF), and thrombospondin-1 (TSP-1). Exposure of human (MIO-M1) and guinea-pig Müller cells to hypoxia resulted in a decreased release of TGF-beta2 and PEDF but in an elevated secretion of TSP-1. When retinal endothelial cells were exposed to VEGF/anti-angiogenic factor ratios mimicking those found in culture media of Müller cells under normoxia or hypoxia, their proliferation was significantly inhibited by TGF-beta2, PEDF or TSP-1. Thus Müller cells may provide a permanent anti-proliferative condition for retinal endothelial cells.

Analysis of Variance↗

PubMed2004

Under stress, the absence of intermediate filaments from Müller cells in the retina has structural and functional consequences.

In epithelial and muscle cells, intermediate filaments (IFs) are important for resistance to mechanical stress. The aim of this study was to elucidate whether IFs are also important for providing resistance to mechanical stress in the Müller cells of the retina and whether this has any pathophysiological consequences. We used mice deficient in IF proteins glial fibrillary acidic protein and/or vimentin (GFAP(-/-), Vim(-/-) and GFAP(-/-) Vim(-/-)), and stress on the retina was applied by excision of the eyes immediately post mortem (compared with in situ fixation) or by inducing a neovascular response to oxygen-induced retinopathy (OIR). The structure of unchallenged retinas was normal, but mechanical stress caused local separation of the inner limiting membrane (ILM) and adjacent tissue from the rest of the retina in GFAP(-/-) Vim(-/-) mice and, to a lesser extent, in Vim(-/-) mice. This detachment occurred within the endfeet of Müller cells, structures normally rich in IFs but IF-free in GFAP(-/-) Vim(-/-) mice. Hypoxia-induced neovascularization was comparable in all groups of mice with respect to the retinal surface area occupied by new vessels. However, the vessels traversed the ILM and penetrated the vitreous body less frequently than in wild-type retinas (31-55% in Vim(-/-), 66-79% in GFAP(-/-) Vim(-/-)). We conclude that IFs are important for maintaining the mechanical integrity of Müller-cell endfeet and the inner retinal layers under a mechanical challenge. Furthermore, the absence of IFs in Müller cells leads to an abnormal response of the vascular system to ischemia, specifically decreased ability of newly formed blood vessels to traverse the ILM.

Animals↗

PubMed2004

Rabbit retinal organ culture as an in-vitro model of hepatic retinopathy.

BACKGROUND: In patients with liver insufficiency the blood ammonia concentration is elevated, which induces structural and functional retinal alterations referred to as "hepatic retinopathy". The fact that some of these alterations are reversible after timely liver transplantation rationalizes therapeutic/preventive approaches to maintain the retina before a donor organ is available. Here, we describe further elaboration and characterization of our retinal organ culture model. METHODS: Retinal pieces of neonatal rabbits were explanted and cultured for up to 22 days. After 7 days in vitro (DIV7), some of the cultures were exposed to 0.25, 0.5, 1.0, 3.0, or 7.0 mM ammonia for varying periods of time and then studied by light and electron microscopy. RESULTS: Untreated (control) cultures underwent several changes during prolonged culturing; these included increased expression of GFAP and of Bcl-2, and decreased levels of glutamine synthetase, in Müller (glial) cells. However, the retinal layering remained intact and even some retinal ganglion cells survived although their axons had been cut. Exposure to elevated levels of ammonia caused morphologic alterations in the explants compatible with those noted in hepatic retinopathy in vivo. Specifically, we observed neuronal cellular degeneration with destruction of retinal layers and formation of rosettes, as well as decreased expression of intermediate filament proteins, migration of cell nuclei, cell swelling, and up-regulation of glutamine synthetase immunoreactivity in (some) Müller cells. CONCLUSION: Our findings indicate that the organ culture model may be a useful tool for detailed studies on the cellular and subcellular mechanisms underlying hepatic retinopathy and for in vitro testing of measures to alleviate HR symptoms.

Ammonia↗

PubMed2004

Tandem-pore K(+) channels display an uneven distribution in amphibian retina.

Previous studies in retinal glial (Müller) cells have suggested that the dominant membrane currents are mediated by K(+) inward-rectifier (Kir) channels. After blockade of inwardly (Kir) and outwardly (KD and BK) conducting channels, a large K(+) conductance remains, but its nature has not been determined. Tandem-pore K(+) channels are likely candidates for this potassium conductance and the purpose of the present study was to determine, using immunocytochemistry, whether Müller cells express TASK-1, TASK-2, TREK-1 and/or TREK-2 potassium channel subunits. The results reveal that retinal glial cells express TASK-1 and TASK-2 subunits, but not TREK-1 or TREK-2 subunits. Furthermore, the distribution of TASK subunits differs from that of Kir channels and may contribute to the potassium conductance of Müller cells.

Animals↗

PubMed2004

Selective staining by vital dyes of Müller glial cells in retinal wholemounts.

Müller glial cells within the retina may respond to different signaling molecules with an elevation of their intracellular free calcium. To prove the localization of the recorded calcium responses in Müller cells within acutely isolated retinal wholemounts, retinal pieces from adult animals and humans were exposed to different vital dyes just after the calcium imaging records were finished. The dyes, Mitotracker Orange, Mitotracker Green, Celltracker Orange, Celltracker Green, and monochlorobimane, are all selectively taken up by Müller glial cells, while neuronal cells remain largely devoid of the dyes. By using this method, it can be demonstrated that the free calcium alterations within the wholemounts indeed occur within Müller cells. Moreover, the cross-sectional areas of (dye-filled) Müller glial cell bodies, as well as of (dye-free) neuronal cell bodies, can be measured in retinal wholemounts, and the spatial densities of both types of cells can be determined. The vital dye loading of Müller cells may facilitate investigations of stimulus-induced alterations of retinal glial cell physiology and morphology.

Animals↗

PubMed2004

Electrophysiological properties of retinal Müller glial cells from myelin mutant rat.

The structural and functional similarities between Müller cells and oligodendrocytes prompted the present study of the electrophysiological properties of Müller (glia) cells obtained from the retinae of control and myelin mutant taiep rats during the postnatal developmental period (P12-P180). The whole-cell configuration of the patch-clamp technique was used to characterize the general properties and the K+ currents from dissociated Müller cells. During the first 3 weeks of life, a decrease of the membrane resistance and an increase of the membrane potential were observed in Müller cells from both control and taiep rats. However, Müller cells from taiep rats never achieved the very negative membrane potential (-50 mV vs -80 mV) and the low membrane resistance characteristic for control cells. Furthermore, Müller cells displayed increased inward and outward K+ currents during postnatal development up to P30/60 in controls; however, in taiep rats, this increase ceased at P20/30, and low-amplitude currents persisted into adulthood. These results provide first evidence of physiological changes in retinal Müller cells as a consequence of a myelin mutation causing a progressive deterioration of the central nervous system (CNS) due to a disturbance of the microtubule network of oligodendrocytes. We hypothesize that the progressive dysmyelination process of the optic nerve, accompanied by functional deficits of retinal neurons (e.g., ganglion cells), induces physiological alterations of Müller cells.

Animals↗

PubMed2004

GABA(A) receptors in Müller glial cells of the human retina.

The present study was aimed at characterizing the GABA(A) receptor-mediated currents in acutely isolated glial (Müller) cells of the human retina and investigating their subcellular localization across the Müller cell membrane. Extracellular application of GABA evoked two current responses in human Müller cells: a fast transient GABA(A) receptor-mediated current that inactivated within 10 s and that was independent of extracellular Na(+), and a sustained current that was dependent on extracellular Na(+) and that was mediated by high-affinity GABA transporters. The receptor current was half-maximally activated at a GABA concentration of 32 microM, while the transporter current showed an affinity constant of 7.9 microM GABA. The receptor currents were blocked by bicuculline and picrotoxin and were also activated by muscimol or by other amino acids. The receptor currents are Cl(-) currents, as indicated by the close relationship between the reversal potential of these currents and the Cl(-) equilibrium potential. Using perforated-patch recordings, a mean intracellular Cl(-) concentration of 37 +/- 12 mM was determined in human Müller cells. Using electrophysiological and fluorescence imaging methods, it was revealed that GABA(A) receptors are unevenly distributed across the Müller cell membrane, with higher densities at the endfoot, at the soma, and at the distal sclerad end of the cells. It is concluded that GABA(A) receptor expression may allow a sensing of retinal GABAergic neuronal signal transmission by Müller cells.

Action Potentials↗

PubMed2004

A potassium channel-linked mechanism of glial cell swelling in the postischemic retina.

The cellular mechanisms underlying glial cell swelling, a central cause of edema formation in the brain and retina, are not yet known. Here, we show that glial cells in the postischemic rat retina, but not in control retina, swell upon hypotonic stress. Swelling of control cells could be evoked when their K(+) channels were blocked. After transient ischemia, glial cells strongly downregulated their K(+) conductance and their prominent Kir4.1 protein expression at blood vessels and the vitreous body. In contrast, the expression of the aquaporin-4 (AQP4) (water channel) protein was only slightly altered after ischemia. Activation of D(2) dopaminergic receptors prevents the hypotonic glial cell swelling. The present results elucidate the coupling of transmembraneous water fluxes to K(+) currents in glial cells and reveal the role of altered K(+) channel expression in the development of cytotoxic edema. We propose a mechanism of postischemic glial cell swelling where a downregulation of their K(+) conductance prevents the emission of intracellularly accumulated K(+) ions, resulting in osmotically driven water fluxes from the blood into the glial cells via aquaporins. Inhibition of these water fluxes may be beneficial to prevent ischemia-evoked glial cell swelling.

Animals↗

PubMed2004

Peeling of the basal membrane in the human retina: ultrastructural effects.

PURPOSE: To study the effects of internal limiting membrane (ILM) peeling, usually performed in cases of macular hole formation, on the structural integrity of the human retina. DESIGN: Experimental study. MATERIAL: Two human donor eyes. METHODS: A human donor retina was subjected to ILM peeling shortly after enucleation, fixed, and studied by electron microscopy. MAIN OUTCOME MEASURES: Electron microscopic findings. RESULTS: Within the peeled area, and even at its margins, a substantial number of Müller (glial) cell endfeet and vitreal Müller cell processes was severely damaged. However, many glial cells remained intact, and the cell bodies of the injured cells showed no signs of destruction. CONCLUSIONS: We have shown that ILM peeling results in minor, but demonstrable, damage of the adjacent retina. Clinical studies are required to demonstrate unequivocally that ILM peeling does not induce functional deficits rather than improvement of visual function.

Basement Membrane↗

PubMed2004

The effects of axotomy on neurons and satellite glial cells in mouse trigeminal ganglion.

Damage to peripheral nerves induces ectopic firing in sensory neurons, which can contribute to neuropathic pain. As most of the information on this topic is on dorsal root ganglia we decided to examine the influence of infra-orbital nerve section on cells of murine trigeminal ganglia. We characterized the electrophysiological properties of neurons with intracellular electrodes. Changes in the coupling of satellite glial cells (SGCs) were monitored by intracelluar injection of the fluorescent dye Lucifer yellow. Electrophysiology of SGCs was studied with the patch-clamp technique. Six to eight days after axotomy, the percentage of neurons that fire spontaneously increased from 1.6 to 12.8%, the membrane depolarized from -51.1 to -45.5 mV, the percentage of cells with spontaneous potential oscillations increased from 19 to 37%, the membrane input resistance decreased from 44.4 to 39.5 MOmega, and the threshold for firing an action potential decreased from 0.61 to 0.42 nA. These changes are consistent with increased neuronal excitability. SGCs were mutually coupled around a given neuron in 21% of the cases, and to SGCs around neighboring neurons in only 4.8% of the cases. After axotomy these values increased to 37.1 and 25.8%, respectively. After axotomy the membrane resistance of SGCs decreased from 101 MOmega in controls to 40 MOmega, possibly due to increased coupling among these cells. We conclude that axotomy affects both neurons and SGCs in the trigeminal ganglion. The increased neuronal excitability and ectopic firing may play a major role in neuropathic pain.

Action Potentials↗

PubMed2004

Glial cell expression of hepatocyte growth factor in vitreoretinal proliferative disease.

The hepatocyte growth factor (HGF) has been crucially implicated in the development of proliferative retinal diseases; however, it is unclear whether retinal glial cells express or respond to HGF. Therefore, we examined the expression of HGF and of the receptor for HGF, c-Met, by immunohistochemical costaining with glial fibrillary acidic protein (GFAP) in epiretinal membranes of patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), respectively. Furthermore, it was determined whether cells of the human retinal glial cell line, MIO-M1, secrete HGF protein, and whether HGF stimulates proliferation and chemotaxis, and secretion of the vascular endothelial growth factor (VEGF). Neuroretinas of patients with PVR express elevated mRNA level for HGF in comparison to control retinas. In epiretinal membranes of patients with PVR or PDR, immunoreactivity for HGF and for c-Met, respectively, partially colocalized with immunoreactivity for GFAP. Fetal bovine serum and basic fibroblast growth factor, but not heparin-binding epidermal or platelet-derived growth factors, evoked HGF secretion by cultured retinal glial cells. HGF displayed only a marginal effect on cell proliferation while it stimulated chemotaxis. HGF promoted the secretion of VEGF, via activation of the phosphatidylinositol-3 kinase. It is concluded that glial cells in epiretinal membranes express both HGF protein and c-Met receptors. The results suggest an autocrine/paracrine role of HGF in glial cell responses during proliferative vitreoretinal disorders as well as in retinal neovascularization, by stimulating of VEGF release.

Adolescent↗

PubMed2004

Contrary effects of cytokines on mRNAs of cell cycle- and ECM-related proteins in hRPE cells in vitro.

PURPOSE: Retinal pigment epithelial (RPE) cells play a pivotal role in the pathogenesis of proliferative vitreoretinopathy (PVR). As a result of a breakdown of the blood-retina barrier, growth factors obtain access to the subretinal space and stimulate several retinal cell types. The aim of the present study was to analyze the effect of several growth factors on the proliferation of human (h)RPE cells, and on the mRNA expression of transcription factors, cell cycle proteins, and extracellular matrix (ECM) proteins. METHODS: hRPE cells were incubated in the presence of TGF-beta1, TGF-beta2, PDGF, VEGF, or bFGF for 24-72 h. Cell proliferation was assessed by determinating BrdU incorporation. Changes in mRNA expression of c-fos, c-myc, PCNA, FEN1, Ki67, collagen III, and collagen IV were investigated by ribonuclease protection assay (RPA). RESULTS: RPE cell proliferation was significantly increased by exposure to PDGF and bFGF for 48 h, and was decreased by application of TGF-beta1 and TGF-beta2 for 48 and 72 h. All the tested growth factors significantly elevated the amounts of c-fos mRNA (after 1 h) and of c-myc mRNA (after 24 h). PDGF and bFGF up-regulated the expression of Ki67 mRNA, and down-regulated that of collagen III and collagen IV mRNA after 24 h. TGF-beta1 and TGF-beta2 decreased the expression of Ki67 mRNA, and increased that of collagen III and collagen IV mRNA. CONCLUSION: Our results show that distinct cytokines may induce contrary effects with respect to proliferation of, and ECM formation by, hRPE cells in vitro. This knowledge may be useful for the development of improved therapeutic approaches.

Cell Cycle Proteins↗

PubMed2004

Expression of LRP1 in retinal pigment epithelial cells and its regulation by growth factors.

PURPOSE: The retinal pigment epithelial (RPE) cells are mitotically inactive under normal conditions, but play a pivotal role in the pathogenesis of proliferative vitreoretinopathy (PVR). Triggered by changes in the concentrations of growth factors, RPE cells reenter the cell cycle, proliferate, and migrate onto the retinal surface, into the subretinal space, and into the vitreous. The receptor for alpha(2)-macroglobulin (low-density lipoprotein receptor-related protein [LRP1], or CD91) is known to be involved in the processes of cell migration and invasion, as well as in the regulation of growth factor homeostasis. The purpose of this study was to investigate the expression of this receptor and its regulation, at the protein and mRNA levels, in human (h)RPE cells. METHODS: The cell surface expression of the receptor was studied by immunocytochemistry and flow cytometry. The endocytosis-related activity of LRP1 in hRPE cells was examined by assessing the uptake of FITC-labeled, methylamine (MA)-treated alpha(2)-M (alpha(2)-M-MA). LRP1 mRNA expression was analyzed by means of the RNase protection assay (RPA) after the hRPE cells were stimulated with the growth factors TGF-beta1, TGF-beta2, PDGF, VEGF (each 10 ng/mL), or bFGF (5 ng/mL). RESULTS: hRPE cells expressed LRP1 on their cell surface. The receptor mediated rapid binding and endocytosis of FITC-labeled alpha(2)-M-MA. The expression of LRP1 mRNA strongly increased on stimulation of the cells with TGF-beta1, TGF-beta2, or VEGF, whereas PDGF or bFGF elicited only minor effects. CONCLUSIONS: The expression of functionally active LRP1 in hRPE cells suggests that the receptor may be involved in cell migration and invasion, as reported for other LRP1-expressing cells. Thus, certain growth factors may control RPE cell migration and invasion in vivo through a regulation of LRP1 expression. As LRP1 mediates the clearance of alpha(2)-M, known to regulate the homeostasis of many cytokines and growth factors, this receptor may be a promising target for therapeutic intervention in PVR.

Aged↗