CN109010798A - A kind of new application of polypeptide - Google Patents
A kind of new application of polypeptide Download PDFInfo
- Publication number
- CN109010798A CN109010798A CN201811080426.7A CN201811080426A CN109010798A CN 109010798 A CN109010798 A CN 109010798A CN 201811080426 A CN201811080426 A CN 201811080426A CN 109010798 A CN109010798 A CN 109010798A
- Authority
- CN
- China
- Prior art keywords
- acid sequence
- amino acid
- polypeptide
- new application
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 93
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 93
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 93
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 50
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 33
- 230000002207 retinal effect Effects 0.000 claims abstract description 33
- 230000006378 damage Effects 0.000 claims abstract description 20
- 206010020772 Hypertension Diseases 0.000 claims abstract description 19
- 210000001525 retina Anatomy 0.000 claims abstract description 14
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 239000002773 nucleotide Substances 0.000 claims abstract description 5
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 5
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- BHONFOAYRQZPKZ-LCLOTLQISA-N chembl269478 Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O)C1=CC=CC=C1 BHONFOAYRQZPKZ-LCLOTLQISA-N 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 38
- 238000000034 method Methods 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 4
- 210000000170 cell membrane Anatomy 0.000 abstract 1
- 230000004410 intraocular pressure Effects 0.000 description 24
- 239000012925 reference material Substances 0.000 description 12
- 230000006698 induction Effects 0.000 description 11
- 230000001154 acute effect Effects 0.000 description 10
- 230000006870 function Effects 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 238000010171 animal model Methods 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 208000003098 Ganglion Cysts Diseases 0.000 description 4
- 241000700161 Rattus rattus Species 0.000 description 4
- 208000005400 Synovial Cyst Diseases 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
- 229910052753 mercury Inorganic materials 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 230000004112 neuroprotection Effects 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 210000003994 retinal ganglion cell Anatomy 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 206010057430 Retinal injury Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 210000002159 anterior chamber Anatomy 0.000 description 2
- 230000002424 anti-apoptotic effect Effects 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000005252 bulbus oculi Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 210000002592 gangliocyte Anatomy 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000009993 protective function Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
- -1 Cobalt amine Chemical class 0.000 description 1
- 238000011767 DBA/2J (JAX™ mouse strain) Methods 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 206010012565 Developmental glaucoma Diseases 0.000 description 1
- 241000223783 Glaucoma Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010067013 Normal tension glaucoma Diseases 0.000 description 1
- 208000030768 Optic nerve injury Diseases 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 201000001326 acute closed-angle glaucoma Diseases 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229960004774 citicoline sodium Drugs 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 235000006279 cobamamide Nutrition 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 230000004438 eyesight Effects 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- DVGHHMFBFOTGLM-UHFFFAOYSA-L fluorogold Chemical compound F[Au][Au]F DVGHHMFBFOTGLM-UHFFFAOYSA-L 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000001232 limbus corneae Anatomy 0.000 description 1
- 201000002978 low tension glaucoma Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960005321 mecobalamin Drugs 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000019581 neuron apoptotic process Effects 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- YWAFNFGRBBBSPD-OCMLZEEQSA-M sodium;[[(2r,3s,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound [Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 YWAFNFGRBBBSPD-OCMLZEEQSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The present invention provides a kind of new applications of polypeptide, it is characterized by: the amino acid sequence of the polypeptide includes the amino acid sequence with defencive function, the polypeptide is for reducing damage suffered by retinal ganglial cells in intraocular hypertension course of glaucoma to protect retinal ganglial cells, the amino acid sequence with defencive function of the polypeptide includes amino acid sequence DGIWKASFTTFTVTKYWFYR and carries out modifying derivative amino acid sequence on this basis, or the amino acid sequence with defencive function of the polypeptide is artificial synthesized amino acid sequence either using nucleotide as the amino acid sequence of templated synthesis, the polypeptide further includes the amino acid sequence with transmembrane ability, the amino acid sequence with transmembrane ability is used for the cell membrane across retina cell Into cell.The new application of polypeptide of the present invention is to protect retinal ganglial cells with a kind of method of biology; reduce side effect; and due to further including the amino acid sequence with transmembrane ability, so that the amino acid sequence with defencive function can rapidly protect retinal ganglial cells.
Description
Technical field
The present invention relates to a kind of new applications of polypeptide, more particularly to polypeptide is used to reduce in intraocular hypertension course of glaucoma and is regarded
Damage suffered by retinal ganglion cells is to protect retinal ganglial cells.
Background technique
Glaucoma is to lose the one kind being characterized with progressive eye optic neuropathy and adjoint irreversibility visual function
Disease.It is estimated that will have about 80,000,000 glaucoma patients to the year two thousand twenty whole world, China to the year two thousand twenty will have about 22,000,000 glaucomas
Patient.Glaucoma has become the blinding eye disease of global second, wherein having one third or so is caused by intraocular hypertension.
Glaucoma is a kind of common ophthalmological disorder for seriously endangering eyesight, and clinically essential therapeutic arsenals are intraocular pressure controls at present
System and neuroprotection.
Hypotensive agents object is broadly divided into: 1, β adrenergic receptor retarding agent;2, prostaglandin derivating agent;3, adrenal gland energy
Receptor stimulating agent (sympathetic transmitter releasers);4, carbonic anhydrase inhibitor;5, high osmotic agent.
But the use of hypotensive agents object can only reduce the intraocular hypertension of glaucoma patient, and intraocular pressure is made to maintain normal range (NR) one
Under, the lesions such as the optic cell damaged cannot be reversed.
Another kind is optic nerve protection drug, and experimental study is more, but by the less of clinical test application, mainly there is first
Cobalt amine, Citicoline sodium tablets etc., Mecobalamin are a kind of endogenic cobamamides, one carbon unit circulation are participated in, for view
Repairing of neural injury plays the role of comfort property, and C14H25N4NaO11P2 participates in the biosynthesis of internal lecithin, belongs to cerebral metabolism and swashs
Agent living, can increase cerebral blood flow, improve brain circulation, repair optic nerve injury without basic effect.
Summary of the invention
Based on the deficiencies of the prior art, inefficiency, the purpose of innovation and creation of the present invention provide a kind of new application of polypeptide,
Polypeptide is used to reduce damage suffered by retinal ganglial cells in intraocular hypertension course of glaucoma to protect retina refreshing
Through ganglion cell.
To achieve the goals above, the present invention provides a kind of new applications of polypeptide, it is characterised in that: the ammonia of the polypeptide
Base acid sequence includes the amino acid sequence with defencive function, and the polypeptide is for reducing retina in intraocular hypertension course of glaucoma
Damage suffered by gangliocyte is to protect retinal ganglial cells.
The improvement of new application as polypeptide of the present invention, the described of the polypeptide of the new application of polypeptide of the present invention have guarantor
The amino acid sequence of protective function includes amino acid sequence DGIWKASFTTFTVTKYWFYR and carries out modification institute on this basis
Derivative amino acid sequence.
The improvement of new application as polypeptide of the present invention, the described of the polypeptide of the new application of polypeptide of the present invention have guarantor
The amino acid sequence of protective function is artificial synthesized amino acid sequence either using nucleotide as the amino acid sequence of templated synthesis.
The improvement of new application as polypeptide of the present invention, the polypeptide of the new application of polypeptide of the present invention further includes having
The amino acid sequence of transmembrane ability, the amino acid sequence with transmembrane ability are used for across retina.
The improvement of new application as polypeptide of the present invention, the polypeptide of the new application of polypeptide of the present invention it is described have wear
The amino acid sequence of film function includes that amino acid sequence RQIKIWFQNRRMKWKK and being modified on this basis derives
Amino acid sequence.
The improvement of new application as polypeptide of the present invention, the polypeptide of the new application of polypeptide of the present invention it is described have wear
The amino acid sequence of film function is the amino acid sequence using nucleotide as templated synthesis.
The improvement of new application as polypeptide of the present invention, the polypeptide of the new application of polypeptide of the present invention it is described have wear
The amino acid sequence of film function is the amino acid sequence with autonomous transmembrane ability.
Compared with prior art, the new application of polypeptide of the present invention is to protect retina neural with a kind of method of biology
Ganglion cell reduces side effect, and due to further including the amino acid sequence with transmembrane ability, so that having defencive function
Amino acid sequence can rapidly protect retinal ganglial cells.
Detailed description of the invention
Fig. 1 is the retinal ganglial cells amount of survival comparison diagram of the new application preferred embodiment 1 of polypeptide of the present invention.
Fig. 2 is the retinal ganglial cells amount of survival statistical result of the new application preferred embodiment 1 of polypeptide of the present invention
Figure.
Fig. 3 is the retinal ganglion cells apoptosis quantitative comparison figure of the new application preferred embodiment 2 of polypeptide of the present invention.
Fig. 4 is the retinal ganglion cells apoptosis quantity statistics result of the new application preferred embodiment 2 of polypeptide of the present invention
Figure.
Fig. 5 is the black rat Ocular hypertensive model schematic diagram of the new application preferred embodiment 1,2 of polypeptide of the present invention.
Specific embodiment
The new application of polypeptide of the present invention is for reducing in intraocular hypertension course of glaucoma suffered by retinal ganglial cells
Damage is to protect retinal ganglial cells.
Acute high intraocular pressure damage is one of the main reason for leading to glaucoma.
The current pathogenesis of glaucoma is not yet clear, and building can preferably simulate the model of disease development process, is
The task of top priority of glaucoma pathogenesis is studied, the building of glaucoma animal model is also always the difficult point in GLAUCOMA RESEARCH field
With hot spot.Currently, there are many methods can simulate the portion link in different type glaucoma pathogenic process, but there is no one
Model can perfectly simulate the overall process of certain glaucoma occurrence and development.
The animal model of common glaucoma has following a few classes:
1, genetic manipulation animal glaucoma model, can be subdivided into Ocular hypertensive model, normal tension glaucoma model and
It is unified that the characteristics of developmental glaucoma model etc., genetic manipulation glaucoma animal model, is that intraocular pressure increases, and can be mass and just
In the Mechanism Study for being directed to specific gene of opening a business, deficiency is that intraocular pressure increases mostly in the specific period, and intraocular pressure elevation amplitude is little,
Such as: DBA/2J Ocular hypertensive model mouse intraocular pressure increases in June to intraocular pressure during December, and intraocular pressure lifting range is in 20-30 millimeters of mercury
Between column.
2, the glaucoma model of intraocular hypertension induction, as episclera vein ligation or coagulation induce intraocular hypertension, damage from laser
The characteristics of room angle induction intraocular hypertension and anterior chamber's injected material blocking room angle induction intraocular hypertension etc., this class model is that intraocular pressure increases width
Degree is big, often causes retinal ganglial cells to damage in a short time, but its deficiency is that certain form of model is unstable, often not
It can induce out the retinal ganglial cells damage that intraocular pressure increases or intraocular pressure raising is caused.
3, induced retinal gangliocyte damages, not with the glaucoma model of intraocular hypertension, such as optic nerve clamp or cutting,
The characteristics of intraocular injection excitatory toxicity substance, this class model of glaucoma caused by ischemical reperfusion injury etc. is induced retinal mind
Warp knuckle cell death is more clear, and method is reliable and stable.But its deficiency is differed greatly with glaucoma pathogenic process.
Present application relates generally to the polypeptide in the application to intraocular injection to the neuroprotection of glaucoma, it is contemplated that this
Polypeptide in the half-life period problem that polypeptide in application is metabolized as therapeutic agent, and previous research in the application is to tumour blood
The influence of pipe and the adjusting of retina stable state;
Selected glaucoma animal model should meet claimed below in correlative study in the application:
1, clearly retinal ganglial cells can be caused to damage in a short time;
2, experimental result stable and consistent has preferable repeatability;
3, damage caused by glaucoma can be preferably simulated in its mechanism of action.
By analyzing above, in conjunction with correlative study laboratory existence conditions in the application, applicant is from common mould at present
Damage from laser induction glaucoma, bead injection induction glaucoma and ischemic perfusion injury induction glaucoma have been selected in type, point
It Chang Shi not construct, by preliminary experiment early period, it is found by the applicant that in C57BL/6 mouse, it is high by the more difficult induced stable of 810 laser
Intraocular pressure, analyzing its reason may be 810 laser to pigment dependence, therefore because plant issue abandons the trial of the model;Thereafter apply
People has attempted using microballon blocking room angle induction intraocular hypertension, by practice it is found by the applicant that model intraocular pressure in mouse increases model
It is with limit, this has greater difference with document report.And the model poor repeatability, it is not able to satisfy the mesh of the correlative study in the application
, therefore abandon the trial of the model.Then, applicant induces acute high intraocular pressure by reverse headgear, so as to cause retina urgency
Property ischemic, after intraocular hypertension 1 hour restore intraocular pressure so that induce retina reperfusion injury.The model can cause bright in a short time
True retinal ganglial cells damage, simulates the partial injury pathophysiological process of acute angle-closure glaucoma, and the mould
Type induces intraocular pressure to increase stable and consistent, and model foundation is simple, and learning curve is short.So the model is the phase carried out in the application
It closes and studies relatively good glaucoma animal model.
Experiment is C57 black mice with black rat in the application related embodiment, and leading vitreous body of eye chamber injects this Shen
Please in polypeptide or reference material, after half an hour, pass through reverse headgear and maintain intraocular pressure to 110 millimetress of mercury, acute high intraocular pressure induction
It treat retinal ischemic 1 hour, then pulls out reverse headgear needle, restores intraocular pressure to eyeball is collected after normal level 2 days, slice is done
TUNEL dyeing, observes retinal cell apoptosis situation.
TUNEL method is to detect the universal method of non-living body retinal damage in biomedicine.
TUNEL method, that is, terminal dexynucleotidyl transferaseTdT-mediated dUTP nick
End labeling, is translated as the dUTP Nick End marker determination method of terminal deoxynucleotidyl transferase mediation, and also referred to as DNA is disconnected
The situ end labeling split, the 3 '-OH that this method can be broken DNA molecular in notch carry out labeled in situ, by one kind
Observable marker, such as fluorescein, the 3 ' ends-OH that can be generated in the core DNA to apoptotic cell carry out labeled in situ, and use is glimmering
Light microscope can be observed.
In the application related embodiment experiment reference material refer to only with transmembrane ability amino acid sequence without
Amino acid sequence with defencive function.
With reference to Fig. 1 and Fig. 2, the preferred embodiment 1 of the new application of the present invention is described in detail polypeptide.
By 7 days after FG, that is, fluorogold retrogradation marker retinal ganglial cells, applicant was in control group and the application
The polypeptide group polypeptide in the polypeptide reference material and the application into 2 μ l the application of intravitreal respectively, built after 4 hours
Vertical acute high IOP model.
It is as follows to establish acute high IOP model concrete operations: after anesthesia, physiological saline infusion bottle being hung on away from small rathole
It is about 110 millimetress of mercury after intraocular pressure converts at ball vertical height 150cm, patient's left hand holds the slightly fixed eyeball of mouse of tweezer, the right hand
The infusion niidl inclined-plane of 30G connection perfusion tube is pierced at corneoscleral junction to right side of mice camera oculi anterior upward.Slightly stop at this time
, it is further continued for being pierced into infusion niidl when the physiological saline that mouse anterior chamber is flowed into is full, stop when entering about 2-3 millimeters of length
Only.Fixed needle prevents syringe needle from causing piercing to damage in iris and crystalline lens etc..Pay attention to the complete stroke thermal insulating from after mouse anesthesia,
After intraocular hypertension saline infusions continue 1 hour, perfusion bottle height is turned down, infusion niidl is gently extracted.Mouse sends breeding room back to
Normal raising.
After 3 days, puts to death black rat and collect retina row tile counting retinal ganglial cells quantity.It has been found that
Compared with the polypeptide group in the application, the reference material group retinal ganglial cells quantity of the polypeptide in the application is significantly reduced.
With the reference material group 172.4 ± 3.385 of the polypeptide in the application;N=5 compares, the polypeptide group 232.3 ± 8.340 in the application;
N=6, P=0.0002 retinal ganglial cells quantity increased significantly, and prompt the polypeptide in the application that can improve acute high intraocular pressure
The retinal ganglial cells of induction are survived.As shown in Figure 1, the part of its Green is the retinal ganglial cells of survival,
Fig. 1 is that applicant does secondary result schematic diagram with regard to above-mentioned experiment repeatedly.
With reference to Fig. 3 and Fig. 4, the preferred embodiment 2 of the new application of the present invention is described in detail polypeptide.
In order to verify protective effect of the polypeptide in the application to retinal neuronal cell in acute high intraocular pressure damage, application
Polypeptide group of the people in control group and the application the polypeptide reference material into 2 μ l the application of intravitreal and this Shen respectively
Please in polypeptide, establish acute high IOP model after 4 hours.
After 3 days, execution black rat collects retina and does specificity antiapoptotic cell dyeing, detects retinal cell apoptosis feelings
Condition.It has been found that the polypeptide in the application can substantially reduce acute high eye compared with the reference material group of the polypeptide in the application
The retinal neuronal cell apoptosis quantity for pressing induction, there is significant statistical difference: the reference material group of the polypeptide in the application:
42.73±2.723;Polypeptide group in the application: 17.77 ± 2.448;N=5, p=0.0001, meanwhile, applicant have observed that special
Anisotropic apoptotic cell staining positive cells are distributed in each major nerve layer of retina.
In order to study the polypeptide in the application to the rule of each confluent monolayer cells neuroprotection of retina, applicant is to this Shen
Please in polypeptide group and the application in the reference material group-specific apoptotic cell staining positive cells number of polypeptide be layered
Statistics, it has been found that the reference material group of the polypeptide of GCL ganglion-cell layer in this application: 6.671 ± 0.8828, this Shen
Please in polypeptide group: 3.233 ± 0.7314, n=5, p=0.0171;The reference material of the polypeptide of INL inner nuclear layer in this application
Group: 20.24 ± 2.183, the polypeptide group in the application: 5.867 ± 0.9286, n=5, p=0.0003 and this Shen of ONL outer nuclear layer
Please in polypeptide reference material group 15.96 ± 2.245, the polypeptide group 8.567 ± 1.378 in the application, n=5, p=0.0230.
In each layer, the polypeptide group specificity antiapoptotic cells staining positive cell quantity in the application is compared with the control of the polypeptide in the application
Object group is few, and the polypeptide in the application is prompted to can be reduced the retinal damage of acute high intraocular pressure induction.As shown in figure 3, its Green
Part be apoptosis retinal neuronal cell, Fig. 3 is that applicant does secondary result schematic diagram with regard to above-mentioned experiment repeatedly.
Compared with prior art, the new application of polypeptide of the present invention is to protect retina neural with a kind of method of biology
Ganglion cell reduces side effect, and due to further including the amino acid sequence with transmembrane ability, so that having defencive function
Amino acid sequence can rapidly protect retinal ganglial cells.
Above disclosed is only presently preferred embodiments of the present invention, cannot limit the right of the present invention with this certainly
Range, therefore according to equivalent variations made by scope of the present invention patent, still belong to the scope that the present invention is covered.
Claims (8)
1. a kind of new application of polypeptide, it is characterised in that: the amino acid sequence of the polypeptide includes the amino with defencive function
Acid sequence, the polypeptide is for reducing damage suffered by retinal ganglial cells in intraocular hypertension course of glaucoma to protect
Retinal ganglial cells.
2. the new application of polypeptide according to claim 1, it is characterised in that: the polypeptide it is described with defencive function
Amino acid sequence includes amino acid sequence DGIWKASFTTFTVTKYWFYR and carries out modifying derivative ammonia on this basis
Base acid sequence.
3. the new application of polypeptide according to claim 1, it is characterised in that: the polypeptide it is described with defencive function
Amino acid sequence is artificial synthesized amino acid sequence either using nucleotide as the amino acid sequence of templated synthesis.
4. the new application of polypeptide according to claim 2 or 3, it is characterised in that: the polypeptide further includes having to wear film
The amino acid sequence of function, the amino acid sequence with transmembrane ability are used for across retina.
5. the new application of polypeptide according to claim 4, it is characterised in that: the polypeptide it is described with transmembrane ability
Amino acid sequence includes amino acid sequence RQIKIWFQNRRMKWKK and carries out modifying derivative amino acid on this basis
Sequence.
6. the new application of polypeptide according to claim 4, it is characterised in that: the polypeptide it is described with transmembrane ability
Amino acid sequence is the amino acid sequence using nucleotide as templated synthesis.
7. the new application of polypeptide according to claim 5, it is characterised in that: the polypeptide it is described with transmembrane ability
Amino acid sequence is the amino acid sequence with autonomous transmembrane ability.
8. the new application of polypeptide according to claim 6, it is characterised in that: the polypeptide it is described with transmembrane ability
Amino acid sequence is the amino acid sequence with autonomous transmembrane ability.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811080426.7A CN109010798A (en) | 2018-09-17 | 2018-09-17 | A kind of new application of polypeptide |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811080426.7A CN109010798A (en) | 2018-09-17 | 2018-09-17 | A kind of new application of polypeptide |
Publications (1)
Publication Number | Publication Date |
---|---|
CN109010798A true CN109010798A (en) | 2018-12-18 |
Family
ID=64621893
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811080426.7A Pending CN109010798A (en) | 2018-09-17 | 2018-09-17 | A kind of new application of polypeptide |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109010798A (en) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020127198A1 (en) * | 1999-08-24 | 2002-09-12 | Rothbard Jonathan B. | Compositions and methods for enhancing drug delivery across and into epithelial tissues |
CN101711863A (en) * | 2009-11-20 | 2010-05-26 | 中国人民解放军第三军医大学第三附属医院 | Vaccine eye drops used for treating and preventing glaucoma and preparation method |
US20150141340A1 (en) * | 2012-06-04 | 2015-05-21 | Yale University | Method of treating and preventing ocular angiogenesis |
CN104861058A (en) * | 2014-02-26 | 2015-08-26 | 上海市第一人民医院 | Novel polypeptide with nerve protection function |
CN105017406A (en) * | 2014-04-21 | 2015-11-04 | 上海市第一人民医院 | Novel polypeptide with nerve protection function |
CN105263948A (en) * | 2013-03-15 | 2016-01-20 | 得克萨斯州大学系统董事会 | Inhibition of pulmonary fibrosis with Nutlin-3a and peptides |
-
2018
- 2018-09-17 CN CN201811080426.7A patent/CN109010798A/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020127198A1 (en) * | 1999-08-24 | 2002-09-12 | Rothbard Jonathan B. | Compositions and methods for enhancing drug delivery across and into epithelial tissues |
CN101711863A (en) * | 2009-11-20 | 2010-05-26 | 中国人民解放军第三军医大学第三附属医院 | Vaccine eye drops used for treating and preventing glaucoma and preparation method |
US20150141340A1 (en) * | 2012-06-04 | 2015-05-21 | Yale University | Method of treating and preventing ocular angiogenesis |
CN105263948A (en) * | 2013-03-15 | 2016-01-20 | 得克萨斯州大学系统董事会 | Inhibition of pulmonary fibrosis with Nutlin-3a and peptides |
CN104861058A (en) * | 2014-02-26 | 2015-08-26 | 上海市第一人民医院 | Novel polypeptide with nerve protection function |
CN105017406A (en) * | 2014-04-21 | 2015-11-04 | 上海市第一人民医院 | Novel polypeptide with nerve protection function |
Non-Patent Citations (2)
Title |
---|
BO O ZHOU等: "Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1", 《ELIFE》 * |
LIWEI ZHANG等: "Caveolin-1 Protects Retinal Ganglion Cells against Acute Ocular Hypertension Injury via Modulating Microglial Phenotypes and Distribution and Activating AKT pathway", 《SCIENTIFIC REPORTS》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Minckler et al. | Orthograde and retrograde axoplasmic transport during acute ocular hypertension in the monkey. | |
Kubota et al. | Decreased choroidal thickness in eyes with secondary angle closure glaucoma. An aetiological factor for deep retinal changes in glaucoma? | |
Abbott et al. | Evaluation of retinal nerve fiber layer thickness and axonal transport 1 and 2 weeks after 8 hours of acute intraocular pressure elevation in rats | |
Tso et al. | Experimental macular edema after lens extraction. | |
Sharif | Therapeutic drugs and devices for tackling ocular hypertension and glaucoma, and need for neuroprotection and cytoprotective therapies | |
Lewczuk et al. | Schlemm's canal: the outflow ‘vessel’ | |
CN101683343A (en) | Method of using (2-imidazolin-2-ylamino) quinoxalines in treating neural injury | |
Rittenhouse et al. | Microdialysis and drug delivery to the eye | |
Gu et al. | Real-time monitoring of suprachoroidal space (SCS) following SCS injection using ultra-high resolution optical coherence tomography in guinea pig eyes | |
Kaufman et al. | Presbyopia and glaucoma: Two diseases, one pathophysiology? The 2017 Friedenwald lecture | |
CN108210520A (en) | Open-angle glaucoma method for building animal model and its application | |
CN109330732A (en) | Establishment and application of a mouse model of herpes simplex virus keratitis | |
CN101797223B (en) | Huperzine A ophthalmic preparation and its application | |
CN109010798A (en) | A kind of new application of polypeptide | |
Toris | Aqueous humor dynamics and intraocular pressure elevation | |
JP2014510115A (en) | Ophthalmic formulation based on PACAP (pituitary adenylate cyclase activating polypeptide) that restores normal visual function in early glaucoma | |
Lee et al. | Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) antibody via Tower Microneedle | |
Dawidek et al. | Beta-adrenergic receptors in human anterior optic nerve: an autoradiographic study | |
Liu et al. | Neuroprotective effect of compound anisodine in a mouse model with chronic ocular hypertension | |
CN111494354B (en) | Use of ABCA1 agonist in preparing medicine for treating eye diseases | |
Algvere et al. | Drainage of microspheres and RBCs from the vitreous of aphakic and phakic eyes | |
Zhong | A modified chronic ocular hypertension rat model for retinal ganglion cell neuroprotection | |
CN109806253A (en) | Application and method of L-aspartate β-hydroxamate in the preparation of drugs for inhibiting choroidal neovascularization | |
CN106389470A (en) | Stem cell preparation, method for preparing same and application of stem cell preparation | |
Hsu et al. | Surgical removal of vitreous: its effect on intraocular fibroblast proliferation in the rabbit |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181218 |