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Kidney International Jun 2016Podocytes maintain the glomerular filtration barrier, and the stability of this barrier depends on their highly differentiated postmitotic phenotype, which also defines... (Review)
Review
Podocytes maintain the glomerular filtration barrier, and the stability of this barrier depends on their highly differentiated postmitotic phenotype, which also defines the particular vulnerability of the glomerulus. Recent podocyte biology and gene disruption studies in vivo indicate a causal relationship between abnormalities of single podocyte molecules and proteinuria and glomerulosclerosis. Podocytes live under various stresses and pathological stimuli. They adapt to maintain homeostasis, but excessive stress leads to maladaptation with complex biological changes including loss of integrity and dysregulation of cellular metabolism. Podocyte injury causes proteinuria and detachment from the glomerular basement membrane. In addition to "sick" podocytes and their detachment, our understanding of glomerular responses following podocyte loss needs to address the pathways from podocyte injury to sclerosis. Studies have found a variety of glomerular responses to podocyte dysfunction in vivo, such as disruption of podocyte-endothelial cross talk and activation of podocyte-parietal cell interactions, all of which help us to understand the complex scenario of podocyte injury and its consequences. This review focuses on the cellular aspects of podocyte dysfunction and the adaptive or maladaptive glomerular responses to podocyte injury that lead to its major consequence, glomerulosclerosis.
Topics: Apoptosis; Bowman Capsule; Cell Communication; Cell Differentiation; Endothelial Cells; Glomerular Basement Membrane; Glomerulosclerosis, Focal Segmental; Humans; Oxidative Stress; Podocytes; Proteinuria; Sclerosis; Stress, Mechanical
PubMed: 27165817
DOI: 10.1016/j.kint.2016.01.012 -
Indian Journal of Ophthalmology Sep 2018Lamellar keratoplasty (LK) has revolutionized corneal graft surgery in several ways. Deep anterior LK (DALK) has eliminated risk of failure due to endothelial rejection.... (Review)
Review
Lamellar keratoplasty (LK) has revolutionized corneal graft surgery in several ways. Deep anterior LK (DALK) has eliminated risk of failure due to endothelial rejection. Endothelial keratoplasty (EK) has almost eliminated induced astigmatism and the "weak" graft-host junction as seen with penetrating keratoplasty (PK) and also reduced the risk of endothelial rejection. LK provided new insights into posterior corneal anatomy that led to better understanding and performance of DALK and to the development of another EK procedure, namely pre-Descemet's EK (PDEK). Surgical procedures for LK were further refined based on the improved understanding and are able to deliver better surgical outcomes in terms of structural integrity and long-term patient satisfaction, reducing the need of further surgeries and minimizing patient discomfort. In most specialist centers, anterior lamellar techniques like DALK and EK techniques like Descemet's stripping EK (DSEK) and Descemet's membrane EK (DMEK) have replaced the full-thickness PK where possible. The introduction of microkeratome, femtosecond laser, and PDEK clamp have made LK techniques easier and more predictable and have led to the innovation of another LK procedure, namely Bowman membrane transplant (BMT). In this article, we discuss the evolution of different surgical techniques, their principles, main outcomes, and limitations. To date, experience with BMT is limited, but DALK has become the gold standard for anterior LK. The EK procedures too have undergone a rapid transition from DSEK to DMEK and PDEK emerging as a viable option. Ultrathin-DSEK may still have a role in modern EK.
Topics: Cornea; Corneal Diseases; Humans; Keratoplasty, Penetrating; Visual Acuity
PubMed: 30127133
DOI: 10.4103/ijo.IJO_95_18 -
F1000Research 2016Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbor cells of the Bowman's capsule. When it comes to glomerular... (Review)
Review
Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbor cells of the Bowman's capsule. When it comes to glomerular filtration, podocytes play an active role in preventing plasma proteins from entering the urinary ultrafiltrate by providing a barrier comprising filtration slits between foot processes, which in aggregate represent a dynamic network of cellular extensions. Foot processes interdigitate with foot processes from adjacent podocytes and form a network of narrow and rather uniform gaps. The fenestrated endothelial cells retain blood cells but permit passage of small solutes and an overlying basement membrane less permeable to macromolecules, in particular to albumin. The cytoskeletal dynamics and structural plasticity of podocytes as well as the signaling between each of these distinct layers are essential for an efficient glomerular filtration and thus for proper renal function. The genetic or acquired impairment of podocytes may lead to foot process effacement (podocyte fusion or retraction), a morphological hallmark of proteinuric renal diseases. Here, we briefly discuss aspects of a contemporary view of podocytes in glomerular filtration, the patterns of structural changes in podocytes associated with common glomerular diseases, and the current state of basic and clinical research.
PubMed: 26918173
DOI: 10.12688/f1000research.7255.1 -
Frontiers in Medicine 2021The glomerulus is the functional unit for filtration of blood and formation of primary urine. This intricate structure is composed of the endothelium with its glycocalyx... (Review)
Review
The glomerulus is the functional unit for filtration of blood and formation of primary urine. This intricate structure is composed of the endothelium with its glycocalyx facing the blood, the glomerular basement membrane and the podocytes facing the urinary space of Bowman's capsule. The mesangial cells are the central hub connecting and supporting all these structures. The components as a unit ensure a high permselectivity hindering large plasma proteins from passing into the urine while readily filtering water and small solutes. There has been a long-standing interest and discussion regarding the functional contribution of the different cellular components but the mesangial cells have been somewhat overlooked in this context. The mesangium is situated in close proximity to all other cellular components of the glomerulus and should be considered important in pathophysiological events leading to glomerular disease. This review will highlight the role of the mesangium in both glomerular function and intra-glomerular crosstalk. It also aims to explain the role of the mesangium as a central component involved in disease onset and progression as well as signaling to maintain the functions of other glomerular cells to uphold permselectivity and glomerular health.
PubMed: 35155460
DOI: 10.3389/fmed.2021.740527 -
Orphanet Journal of Rare Diseases Feb 2009The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The... (Review)
Review
The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses, lipidoses, mucolipidoses), and several skin diseases (X-linked ichthyosis, keratosis follicularis spinolosa decalvans). The management of the corneal dystrophies varies with the specific disease. Some are treated medically or with methods that excise or ablate the abnormal corneal tissue, such as deep lamellar endothelial keratoplasty (DLEK) and phototherapeutic keratectomy (PTK). Other less debilitating or asymptomatic dystrophies do not warrant treatment. The prognosis varies from minimal effect on the vision to corneal blindness, with marked phenotypic variability.
Topics: Corneal Dystrophies, Hereditary; Humans
PubMed: 19236704
DOI: 10.1186/1750-1172-4-7 -
Digital Journal of Ophthalmology : DJO Apr 2019Spheroidal degeneration, involving the cornea and/or the conjunctiva, is characterized by amber-colored homogeneous, translucent spherules in the corneal stroma,...
Spheroidal degeneration, involving the cornea and/or the conjunctiva, is characterized by amber-colored homogeneous, translucent spherules in the corneal stroma, Bowman's membrane, and subepithelium. The condition has a higher prevalence in areas with extreme temperatures, low humidity, high wind, and presence of sand. We report the case of a 46-year-old man with a 10-year history of gradual progressive diminution of vision, severe blepharospasm, and photophobia. Examination revealed bilateral plaques of amber-colored nodules covering about half of the cornea. Superficial keratectomy was performed for the lesions in both eyes, leaving an epithelial defect overlying a plane of opaque cornea. Histopathology showed amorphous protein in the anterior stroma, confirming the clinical diagnosis of advanced grade 4 spheroidal degeneration. Visual acuity and other symptoms dramatically improved, and the patient was scheduled for keratoplasty.
Topics: Cornea; Corneal Diseases; Disease Progression; Humans; Keratoplasty, Penetrating; Male; Middle Aged; Visual Acuity
PubMed: 32076391
DOI: 10.5693/djo.02.2019.11.001