Concanavalin A

Last updated
Concanavalin A
3CNA Concanavalin A.png
Crystallographic structure of a tetramer of jack bean concanavalin A (the monomers are colored cyan, green, red, and magenta respectively). Calcium (gold) and manganese cations (grey) are depicted as spheres. [1]
Identifiers
Organism Canavalia ensiformis (jackbean)
SymbolConA
PDB 3CNA
UniProt P81461
Search for
Structures Swiss-model
Domains InterPro

Concanavalin A (ConA) is a lectin (carbohydrate-binding protein) originally extracted from the jack-bean (Canavalia ensiformis). It is a member of the legume lectin family. It binds specifically to certain structures found in various sugars, glycoproteins, and glycolipids, mainly internal and nonreducing terminal α-D-mannosyl and α-D-glucosyl groups. [2] [3] Its physiological function in plants, however, is still unknown. ConA is a plant mitogen, and is known for its ability to stimulate mouse T-cell subsets giving rise to four functionally distinct T cell populations, including precursors to regulatory T cells; [4] a subset of human suppressor T-cells is also sensitive to ConA. [4] ConA was the first lectin to be available on a commercial basis, and is widely used in biology and biochemistry to characterize glycoproteins and other sugar-containing entities on the surface of various cells. [5] It is also used to purify glycosylated macromolecules in lectin affinity chromatography, [6] as well as to study immune regulation by various immune cells. [4]

Contents

Structure and properties

Like most lectins, ConA is a homotetramer: each sub-unit (26.5kDa, 235 amino-acids, heavily glycated) binds a metallic atom (usually Mn2+ and a Ca2+). It has the D2 symmetry. [1] Its tertiary structure has been elucidated, [7] as have the molecular basis of its interactions with metals as well as its affinity for the sugars mannose and glucose [8] are well known.

ConA binds specifically α-D-mannosyl and α-D-glucosyl residues (two hexoses differing only in the alcohol on carbon 2) in terminal position of ramified structures from B-Glycans (rich in α-mannose, or hybrid and bi-antennary glycan complexes). It has 4 binding sites, corresponding to the 4 sub-units. [3] The molecular weight is 104–112 kDa and the isoelectric point (pI) is in the range of 4.5–5.5.

ConA can also initiate cell division (mitogenesis), primarily acting on T-lymphocytes, by stimulating their energy metabolism within seconds of exposure. [9]

Maturation process

ConA and its variants (found in closely related plants) are the only proteins known to undergo a post-translational sequence arrangement known as Circular permutation in proteins whereby the N-terminal half of the conA precursor is swapped to become the C-terminal half in the mature form; all other known circular permutations occur at the genetic level. [10] [11] ConA circular permutation is carried out by jack bean asparaginyl endopeptidase, [12] a versatile enzyme capable of cleaving and ligating peptide substrates at a single active site. [13] To convert conA to the mature form, jack bean asparaginyl endopeptidase cleaves the precursor of conA in the middle and ligates the two original termini.

Biological activity

Concanavalin A interacts with diverse receptors containing mannose carbohydrates, notably rhodopsin, blood group markers, insulin receptors, [14] the immunoglobulins and the carcino-embryonary antigen (CEA). It also interacts with lipoproteins. [15]

ConA strongly agglutinates erythrocytes irrespective of blood-group, and various cancerous cells. [16] [17] [18] It was demonstrated that transformed cells and trypsin-treated normal cells do not agglutinate at 4 °C, thereby suggesting that there is a temperature-sensitive step involved in ConA-mediated agglutination. [19] [20]

ConA-mediated agglutination of other cell types has been reported, including muscle cells, [21] B-lymphocytes (through surface immunoglobulins), [22] fibroblasts, [23] rat thymocytes, [24] human fetal (but not adult) intestinal epithelial cells, [25] and adipocytes. [26]

ConA is a lymphocyte mitogen. Similar to phytohemagglutinin (PHA), it is a selective T cell mitogen relative to its effects on B cells. PHA and ConA bind and cross-link components of the T cell receptor, and their ability to activate T cells is dependent on expression of the T cell receptor. [27] [28]

ConA interacts with the surface mannose residues of many microbes, including the bacteria E. coli , [29] and Bacillus subtilis [30] and the protist Dictyostelium discoideum . [31]

It has also been shown as a stimulator of several matrix metalloproteinases (MMPs). [32]

ConA has proven useful in applications requiring solid-phase immobilization of glycoenzymes, especially those that have proved difficult to immobilize by traditional covalent coupling. Using ConA-couple matrices, such enzymes may be immobilized in high quantities without a concurrent loss of activity or stability. Such noncovalent ConA-glycoenzyme couplings may be relatively easily reversed by competition with sugars or at acidic pH. If necessary for certain applications, these couplings can be converted to covalent bindings by chemical manipulation. [33]

A report from Taiwan (2009) demonstrated potent therapeutic effect of ConA against experimental hepatoma (liver cancer); in the study by Lei and Chang, [34] ConA was found to be sequestered more by hepatic tumor cells, in preference to surrounding normal hepatocytes. Internalization of ConA occurs preferentially to the mitochondria after binding to cell membrane glycoproteins, which triggers an autophagic cell death. ConA was found to partially inhibit tumor nodule growth independent of its lymphocyte activation; the eradication of the tumor in the murine in-situ hepatoma model in this study was additionally attributed to the mitogenic/lymphoproliferative action of ConA that may have activated a CD8+ T-cell-mediated, as well as NK- and NK-T cell-mediated, immune response in the liver. [34]

ConA intravitreal injection can be used in the modeling of proliferative vitreoretinopathy in rats. [35] [36]

Related Research Articles

<span class="mw-page-title-main">Integrin</span> Instance of a defined set in Homo sapiens with Reactome ID (R-HSA-374573)

Integrins are transmembrane receptors that help cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface.

<span class="mw-page-title-main">Lectin</span> Carbohydrate-binding protein

Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in recognition at the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins. Lectins also mediate attachment and binding of bacteria, viruses, and fungi to their intended targets.

An oligosaccharide is a saccharide polymer containing a small number of monosaccharides. Oligosaccharides can have many functions including cell recognition and cell adhesion.

<span class="mw-page-title-main">C3-convertase</span>

C3 convertase belongs to family of serine proteases and is necessary in innate immunity as a part of the complement system which eventuate in opsonisation of particles, release of inflammatory peptides, C5 convertase formation and cell lysis.

Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each other and to their surroundings. CAMs are crucial components in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in generating force and movement and consequently ensuring that organs are able to execute their functions normally. In addition to serving as "molecular glue", CAMs play important roles in the cellular mechanisms of growth, contact inhibition, and apoptosis. Aberrant expression of CAMs may result in a wide range of pathologies, ranging from frostbite to cancer.

Biological crosstalk refers to instances in which one or more components of one signal transduction pathway affects another. This can be achieved through a number of ways with the most common form being crosstalk between proteins of signaling cascades. In these signal transduction pathways, there are often shared components that can interact with either pathway. A more complex instance of crosstalk can be observed with transmembrane crosstalk between the extracellular matrix (ECM) and the cytoskeleton.

Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca2+-dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids that are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) of oligosaccharide origin. Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis, or inhibition of microbial growth. Other functions of collectins are modulation of inflammatory, allergic responses, adaptive immune system and clearance of apoptotic cells.

Pokeweed mitogen is a mitogen derived from the roots of Phytolacca americana. It functions as a lectin and a mitotic stimulus for the division of lymphocytes.

<span class="mw-page-title-main">Galectin</span> Protein family binding to β-galactoside sugars

Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, which can be bound to proteins by either N-linked or O-linked glycosylation. They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding. There have been about 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11 and -15 are uniquely found in sheep and goats. Members of the galectin family have also been discovered in other mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. They have distinct but overlapping distributions but found primarily in the cytosol, nucleus, extracellular matrix or in circulation. Although many galectins must be secreted, they do not have a typical signal peptide required for classical secretion. The mechanism and reason for this non-classical secretion pathway is unknown.

<span class="mw-page-title-main">Langerin</span>

Langerin (CD207) is a type II transmembrane protein which is encoded by the CD207 gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langerhans cells (LCs) and in mice also on dermal interstitial CD103+ dendritic cells (DC) and on resident CD8+ DC in lymph nodes.

<span class="mw-page-title-main">Insulin-like growth factor 2 receptor</span> Protein-coding gene in the species Homo sapiens

Insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR) is a protein that in humans is encoded by the IGF2R gene. IGF2R is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.

The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes. It is the first member of a family of endocytic receptors that includes Endo180 (CD280), M-type PLA2R, and DEC-205 (CD205).

Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and α-actinin.

<span class="mw-page-title-main">ICAM3</span> Mammalian protein found in Homo sapiens

Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.

<span class="mw-page-title-main">CD69</span> Human lectin protein

CD69 is a human transmembrane C-Type lectin protein encoded by the CD69 gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is also implicated in T cell differentiation as well as lymphocyte retention in lymphoid organs.

<span class="mw-page-title-main">Signal-regulatory protein alpha</span> Protein-coding gene in the species Homo sapiens

Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.

<span class="mw-page-title-main">LMAN1</span> Protein-coding gene in the species Homo sapiens

Protein ERGIC-53 also known as ER-Golgi intermediate compartment 53 kDa protein or lectin mannose-binding 1 is a protein that in humans is encoded by the LMAN1 gene.

<span class="mw-page-title-main">Hemagglutinin</span>

In molecular biology, hemagglutinins are receptor-binding membrane fusion glycoproteins produced by viruses in the Paramyxoviridae and Orthomyxoviridae families. Hemagglutinins are responsible for binding to receptors on red blood cells to initiate viral attachment and infection. The agglutination of red cells occurs when antibodies on one cell bind to those on others, causing amorphous aggregates of clumped cells.

<span class="mw-page-title-main">Cell surface receptor</span> Class of ligand activated receptors localized in surface of plama cell membrane

Cell surface receptors are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

Feline coronavirus (FCoV) is a positive-stranded RNA virus that infects cats worldwide. It is a coronavirus of the species Alphacoronavirus 1, which includes canine coronavirus (CCoV) and porcine transmissible gastroenteritis coronavirus (TGEV). FCoV has two different forms: feline enteric coronavirus (FECV), which infects the intestines, and feline infectious peritonitis virus (FIPV), which causes the disease feline infectious peritonitis (FIP).

References

  1. 1 2 PDB: 3CNA ​; Hardman KD, Ainsworth CF (December 1972). "Structure of concanavalin A at 2.4-A resolution". Biochemistry. 11 (26): 4910–4919. doi:10.1021/bi00776a006. PMID   4638345.
  2. ↑ Goldstein, Irwin J.; Poretz, Ronald D. (2012). "Isolation, physicochemical characterization, and carbohydrate-binding specificity of lectins". In Liener, Irvin E.; Sharon, Nathan; Goldstein, Irwin J. (eds.). The Lectins Properties, Functions and Applications in Biology and Medicine. Elsevier. pp. 33–247. ISBN   978-0-323-14444-5.
  3. 1 2 Sumner JB, Gralën N, Eriksson-Quensel IB (April 1938). "The Molecular Weights of Urease, Canavalin, Concanavalin a and Concanavalin B". Science. 87 (2261): 395–396. Bibcode:1938Sci....87..395S. doi:10.1126/science.87.2261.395. PMID   17746464.
  4. 1 2 3 Dwyer JM, Johnson C (November 1981). "The use of concanavalin A to study the immunoregulation of human T cells". Clinical and Experimental Immunology. 46 (2): 237–249. PMC   1536405 . PMID   6461456.
  5. ↑ Schiefer HG, Krauss H, Brunner H, Gerhardt U (December 1975). "Ultrastructural visualization of surface carbohydrate structures on mycoplasma membranes by concanavalin A". Journal of Bacteriology. 124 (3): 1598–1600. doi:10.1128/JB.124.3.1598-1600.1975. PMC   236075 . PMID   1104592.
  6. ↑ GE Healthcare Life Sciences, Immobilized lectin Archived 2012-03-03 at the Wayback Machine [ full citation needed ]
  7. ↑ Min W, Dunn AJ, Jones DH (April 1992). "Non-glycosylated recombinant pro-concanavalin A is active without polypeptide cleavage". The EMBO Journal. 11 (4): 1303–1307. doi:10.1002/j.1460-2075.1992.tb05174.x. PMC   556578 . PMID   1563347.
  8. ↑ Loris R, Hamelryck T, Bouckaert J, Wyns L (March 1998). "Legume lectin structure". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1383 (1): 9–36. doi:10.1016/S0167-4838(97)00182-9. PMID   9546043.
  9. ↑ Krauss S, Buttgereit F, Brand MD (June 1999). "Effects of the mitogen concanavalin A on pathways of thymocyte energy metabolism". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1412 (2): 129–138. doi: 10.1016/S0005-2728(99)00058-4 . PMID   10393256.
  10. ↑ Carrington DM, Auffret A, Hanke DE (1985). "Polypeptide ligation occurs during post-translational modification of concanavalin A". Nature. 313 (5997): 64–67. Bibcode:1985Natur.313...64C. doi:10.1038/313064a0. PMID   3965973. S2CID   4359482.
  11. ↑ Hendrix RW (April 1991). "Protein carpentry". Current Biology. 1 (2): 71–73. doi:10.1016/0960-9822(91)90280-a. PMID   15336168. S2CID   45963307.
  12. ↑ Nonis SG, Haywood J, Schmidberger JW, Mackie ER, Soares da Costa TP, Bond CS, Mylne JS (August 2021). "Structural and biochemical analyses of concanavalin A circular permutation by jack bean asparaginyl endopeptidase". The Plant Cell. 33 (8): 2794–2811. doi:10.1093/plcell/koab130. PMC   8408470 . PMID   34235541.
  13. ↑ Nonis SG, Haywood J, Mylne JS (April 2021). "Plant asparaginyl endopeptidases and their structural determinants of function". Biochemical Society Transactions. 49 (2): 965–976. doi:10.1042/BST20200908. PMC   8106488 . PMID   33666219.
  14. ↑ Cuatrecasas P, Tell GP (February 1973). "Insulin-like activity of concanavalin A and wheat germ agglutinin--direct interactions with insulin receptors". Proceedings of the National Academy of Sciences of the United States of America. 70 (2): 485–489. Bibcode:1973PNAS...70..485C. doi: 10.1073/pnas.70.2.485 . JSTOR   62526. PMC   433288 . PMID   4510292.
  15. ↑ Harmony JA, Cordes EH (November 1975). "Interaction of human plasma low density lipoprotein with concanavalin A and with ricin". The Journal of Biological Chemistry. 250 (22): 8614–8617. doi: 10.1016/S0021-9258(19)40714-X . PMID   171260.[ permanent dead link ]
  16. ↑ Betton GR (November 1976). "Agglutination reactions of spontaneous canine tumour cells, induced by concanavalin A, demonstrated by an isotopic assay". International Journal of Cancer. 18 (5): 687–696. doi:10.1002/ijc.2910180518. PMID   992901. S2CID   36612952.
  17. ↑ Kakizoe T, Komatsu H, Niijima T, Kawachi T, Sugimura T (June 1980). "Increased agglutinability of bladder cells by concanavalin A after administration of carcinogens". Cancer Research. 40 (6): 2006–2009. PMID   7371036.
  18. ↑ Becker FF, Shurgin A (October 1975). "Concanavalin A agglutination of cells from primary hepatocellular carcinomas and hepatic nodules induced by N-2-fluorenylacetamide". Cancer Research. 35 (10): 2879–2883. PMID   168971.
  19. ↑ Inbar M, Ben-Bassat H, Sachs L (November 1971). "A specific metabolic activity on the surface membrane in malignant cell-transformation". Proceedings of the National Academy of Sciences of the United States of America. 68 (11): 2748–2751. Bibcode:1971PNAS...68.2748I. doi: 10.1073/pnas.68.11.2748 . JSTOR   61219. PMC   389516 . PMID   4330939.
  20. ↑ Sela BA, Lis H, Sharon N, Sachs L (December 1971). "Quantitation of N-acetyl-D-galactosamine-like sites on the surface membrane of normal and transformed mammalian cells". Biochimica et Biophysica Acta (BBA) - Biomembranes. 249 (2): 564–568. doi:10.1016/0005-2736(71)90132-5. PMID   4332414.
  21. ↑ Gartner TK, Podleski TR (December 1975). "Evidence that a membrane bound lectin mediates fusion of L6 myoblasts". Biochemical and Biophysical Research Communications. 67 (3): 972–978. doi:10.1016/0006-291X(75)90770-6. PMID   1201086.
  22. ↑ de Petris S (April 1975). "Concanavalin A receptors, immunoglobulins, and theta antigen of the lymphocyte surface. Interactions with concanavalin A and with Cytoplasmic structures". The Journal of Cell Biology. 65 (1): 123–146. doi:10.1083/jcb.65.1.123. PMC   2111157 . PMID   1092699.
  23. ↑ Noonan KD, Burger MM (October 1973). "The relationship of concanavalin A binding to lectin-initiated cell agglutination". The Journal of Cell Biology. 59 (1): 134–142. doi:10.1083/jcb.59.1.134. PMC   2110924 . PMID   4201706.
  24. ↑ Capo C, Garrouste F, Benoliel AM, Bongrand P, Ryter A, Bell GI (August 1982). "Concanavalin-A-mediated thymocyte agglutination: a model for a quantitative study of cell adhesion". Journal of Cell Science. 56: 21–48. doi:10.1242/jcs.56.1.21. PMID   7166565.
  25. ↑ Weiser MM (August 1972). "Concanavalin A agglutination of intestinal cells from the human fetus". Science. 177 (4048): 525–526. Bibcode:1972Sci...177..525W. doi:10.1126/science.177.4048.525. PMID   5050484. S2CID   23661797.
  26. ↑ Cuatrecasas P (March 1973). "Interaction of wheat germ agglutinin and concanavalin A with isolated fat cells". Biochemistry. 12 (7): 1312–1323. doi:10.1021/bi00731a011. PMID   4696755.
  27. ↑ Weiss A, Shields R, Newton M, Manger B, Imboden J (April 1987). "Ligand-receptor interactions required for commitment to the activation of the interleukin 2 gene". Journal of Immunology. 138 (7): 2169–2176. doi: 10.4049/jimmunol.138.7.2169 . PMID   3104454. S2CID   35173412.
  28. ↑ Kanellopoulos JM, De Petris S, Leca G, Crumpton MJ (May 1985). "The mitogenic lectin from Phaseolus vulgaris does not recognize the T3 antigen of human T lymphocytes". European Journal of Immunology. 15 (5): 479–486. doi:10.1002/eji.1830150512. PMID   3873340. S2CID   21414006.
  29. ↑ Ofek I, Mirelman D, Sharon N (February 1977). "Adherence of Escherichia coli to human mucosal cells mediated by mannose receptors". Nature. 265 (5595): 623–625. Bibcode:1977Natur.265..623O. doi:10.1038/265623a0. PMID   323718. S2CID   4223466.
  30. ↑ Doyle RJ, Birdsell DC (February 1972). "Interaction of concanavalin A with the cell wall of Bacillus subtilis". Journal of Bacteriology. 109 (2): 652–658. doi:10.1128/JB.109.2.652-658.1972. PMC   285189 . PMID   4621684.
  31. ↑ West CM, McMahon D (July 1977). "Identification of concanavalin A receptors and galactose-binding proteins in purified plasma membranes of Dictyostelium discoideum". The Journal of Cell Biology. 74 (1): 264–273. doi:10.1083/jcb.74.1.264. PMC   2109878 . PMID   559679.
  32. ↑ Yu M, Sato H, Seiki M, Thompson EW (August 1995). "Complex regulation of membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation by concanavalin A in MDA-MB-231 human breast cancer cells". Cancer Research. 55 (15): 3272–3277. PMID   7614461.
  33. ↑ Saleemuddin M, Husain Q (April 1991). "Concanavalin A: a useful ligand for glycoenzyme immobilization--a review". Enzyme and Microbial Technology. 13 (4): 290–295. doi:10.1016/0141-0229(91)90146-2. PMID   1367163.
  34. 1 2 Lei HY, Chang CP (January 2009). "Lectin of Concanavalin A as an anti-hepatoma therapeutic agent". Journal of Biomedical Science. 16 (1): 10. doi: 10.1186/1423-0127-16-10 . PMC   2644972 . PMID   19272170.
  35. ↑ Erdiakov AK, Tikhonovich MV, Rzhavina EM, Gavrilova SA (May 2015). "[The characteristics of retina at the development of proliferative vitreoretinopathy in rats after intraocular injection of concanavalin a and dispase]". Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova. 101 (5): 572–585. PMID   26263683.
  36. ↑ Tikhonovich MV, Erdiakov AK, Gavrilova SA (August 2018). "Nonsteroid anti-inflammatory therapy suppresses the development of proliferative vitreoretinopathy more effectively than a steroid one". International Ophthalmology. 38 (4): 1365–1378. doi:10.1007/s10792-017-0594-3. PMID   28639085. S2CID   4017540.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.