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CN105943186A - Establishment method for chronic high intraocular pressure animal model - Google Patents

Establishment method for chronic high intraocular pressure animal model Download PDF

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Publication number
CN105943186A
CN105943186A CN201610249471.5A CN201610249471A CN105943186A CN 105943186 A CN105943186 A CN 105943186A CN 201610249471 A CN201610249471 A CN 201610249471A CN 105943186 A CN105943186 A CN 105943186A
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China
Prior art keywords
intraocular pressure
animal model
schlemm
chronic
building
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CN201610249471.5A
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Chinese (zh)
Inventor
梁远波
胡城
廖娜
徐晶
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Wenzhou Yan Shiguang Development Co Ltd
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Wenzhou Yan Shiguang Development Co Ltd
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Priority to CN201610249471.5A priority Critical patent/CN105943186A/en
Publication of CN105943186A publication Critical patent/CN105943186A/en
Priority to PCT/CN2017/078965 priority patent/WO2017181835A1/en
Priority to JP2018532502A priority patent/JP6505325B2/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61DVETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D1/00Surgical instruments for veterinary use

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Materials For Medical Uses (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Provided is an establishment method for a chronic high intraocular pressure animal model. Through placing materials to block an outflow pathway of aqueous humor by operation, a glaucoma animal model which is increased in intraocular pressure and damaged in optic nerve is made. Increased intraocular pressure is maintained stable, and the intraocular pressure is easy to obtain and operate. The obtained model is advantaged in stable intraocular pressure increasing, low fluctuation, long high intraocular pressure duration time, and controllable target intraocular pressure. The intraocular pressure of the chronic high intraocular pressure animal model made by the method can be regulated according to different Schlemm blocking ranges. According to Schlemm pipe diameters of different animal kinds, fiber conduits in different specifications and dimensions can be selected, so as to complete blocking of the Schlemm pipe, and generate chronic high intraocular pressure models of various kinds of animals. Preferably establishing modeling animals and modeling methods fit with clinic in chronic high intraocular pressure glaucoma mechanism research provides foundation for chronic glaucoma optic nerve injury mechanism.

Description

A kind of method for building up of chronic intraocular hypertension animal model
Technical field
The present invention relates to medical animal model field, be specifically related to the method for building up of a kind of chronic intraocular hypertension animal model.
Background technology
Glaucoma is a kind of irreversibility optic nerve degeneration, for whole world second diseases causing blindness.The pathogenesis of its complexity is the most still not very clear, although Bulbi hypertonia is not the single factor that glaucoma regards infringement, but Bulbi hypertonia is one of factor the most dangerous in Deterioration of Optic Nerve in Glaucoma generation and development mechanism.In GLAUCOMA RESEARCH field, animal model has become important research tool.Glaucoma animal model has important effect for the damage mechanisms and remedy measures being better understood from glaucomatous optic neuropathy.Bulbi hypertonia is the topmost risk factor of Deterioration of Optic Nerve in Glaucoma, so the animal model of most of GLAUCOMA RESEARCH remains induced animal Bulbi hypertonia, and then studies the aspects such as the physiology of glaucoma, pathology, pharmacology.Preferably experimental animal model requires: its construction method is simple, with low cost, it is easy to raise and control, and the intraocular pressure of rising remains stable, and the distinctive pathological change of retina optic nerve occurs.
The animal being currently used for making glaucoma model is low mammal such as grade, mainly has rabbit, Mus, monkey.Although Mus is prone to transgenic technology transformation and breeding, and the structure of rathole is similar with human eye at a lot of aspects, and such as girder, Schlemm pipe, corpus ciliare, retinal vessel etc., but rathole is relatively small, is unfavorable for being operated.The Ocular hypertensive model of the monkey of induced with laser is the optimal Bulbi hypertonia animal model generally acknowledged at present, but because involving great expense, operates more complicated, and domestic application is few.Although lagophthalmos has Morphological Differences with the chamber-angle structure of human eye, but ah outflow passage is identical, has continuous print endotheliocyte liner.And rabbit price is inexpensive, personality is docile, be easily obtained and operate, therefore rabbit is most commonly used for making the laboratory animal of glaucoma model.
It is divided into according to Bulbi hypertonia Forming Mechanism and medicine site of action and acts on angle of anterior chamber (and girder) type, such as injected into anterior chambers hyaluronic acid, methylcellulose, hemocyte, Carbomer liquid, back room injection 5. Chymotrypsin, laser photocoagulation trabecular reticulum, the method such as eyes external corticosteroid hormone;Act on the most conventional scleral surface intravenous injection hypertonic saline method (Morre-Morrison model) of sclera aqueous humor drains intravenous type, burn episcleral aqueous humor drainage vein method (Shareef-Sharma model) and modification method;Additionally, also have the spontaneous mouse of some special germlines and transgenic technology to build glaucoma model, such as the mouse inbred lines of DBA/2J and AKXD-28/Ty, utilize the natural glaucoma model etc. that gene targeting builds.The most various models pathologic in terms of retinal ganglial cells (RGCs), optic nerve, retinal function is changed and be evaluated, assess the Positive and Negative Aspects of various model, preferably build, in chronic intraocular hypertension glaucoma Mechanism Study, the modeling animal agreed with mutually with clinic and modeling method provides foundation, the more mechanism of in-depth study chronic intraocular hypertension glaucoma, provides new thinking for its treatment.
Although the method making Bulbi hypertonia animal model has a lot, but current glaucoma animal model great majority are all acute high IOP models, although intraocular pressure raises, but its Bulbi hypertonia is held time short, and it is big to fluctuate, it is difficult to simulate the characteristic optic nerve lesion of glaucoma.
Summary of the invention
In order to overcome the defect of prior art, the invention provides the method for building up of a kind of chronic intraocular hypertension animal model.
The technical solution that the present invention uses is: the method for building up of a kind of chronic intraocular hypertension animal model, comprise the following steps: animal pattern bondage is lain on the back in operating-table by (1), art eye sterile drape, put eye speculum, rinse conjunctival sac, under art eye conjunctiva after the anesthesia of local profit, do superior rectus traction sutures and fix;
(2) timepiece dial telegoniometer is pressed, in 11 positions to 1 position edge ring bulbar conjunctiva incision, centered by 12 positions, place makees the shallow-layer scleral flap of 1/3 scleral thickness of size 4*4mm with limbus of corneae as substrate, size 3*3mm is done again below shallow-layer scleral flap, the Deep Layer of Sclera lobe of thickness 2/3 scleral thickness, and peel off to cornea direction, find Schlemm to manage and cut Schlemm pipe outer wall;
(3) in Schlemm pipe two ends, polymer hyaluronic acid is injected, fiber duct conduit is passed through opening, in 9 or 3 o ' clock orientation limbus of corneae at 1.0 mm, flat iris direction row paracentesis of anterior chamber, light pressure puncture orifice trailing edge, release water and reduce intraocular pressure, anterior chamber is reduced pressure and fiber duct is inserted after puncturing the broken ends of fractured bone of Schlemm pipe, 360 degree or 270 degree or 180 degree or 90 degree are detoured along Schlemm pipe, cut off conduit, it is placed in Schlemm blocking Schlemm pipe, stop ah outflow, sew up scleral flap, , paracentesis of anterior chamber mouth injection balance saline solution, sew up conjunctival flap, give anti-inflammatory drug, finally set up the animal model that intraocular pressure raises.
Described step (1) use dilution iodophor solution rinse conjunctival sac.
Described step (1) use the lignocaine of 0.4ml 2% carry out profit anesthesia in local under art eye conjunctiva.
Described step (1) use 30G syringe needle inject polymer hyaluronic acid in Schlemm pipe two ends.
In described step (3), fiber duct includes a cylindrical solid conduit, and described tube at one end is spherical structure.
The long 10cm of described fiber duct, diameter 200 μm, the spherical diameter of described tube at one end is 250 μm.
Described fiber duct uses polypropylene material to make.
The invention has the beneficial effects as follows: the invention provides the method for building up of a kind of chronic intraocular hypertension animal model, place material by operation and block its aqueous humor flow pass, intraocular pressure is caused to raise the chronic glaucoma animal model of optic nerve lesion, the chronic intraocular hypertension animal model produced by this method, its intraocular pressure can regulate and control according to the scope difference of blocking Schlemm.And the fiber duct of different specification size can be selected according to different animals kind Schlemm caliber, complete Schlemm blockage, thus produce the ocular hypertension model of many animals type.In chronic intraocular hypertension glaucoma Mechanism Study, preferably build the modeling animal agreed with mutually with clinic and modeling method, provide basis for carrying out chronic glaucoma optic nerve injury mechanism.
Accompanying drawing explanation
Fig. 1 is fiber duct structural representation of the present invention.
Detailed description of the invention
In conjunction with Fig. 1, the present invention is further described: operating procedure: operation needs a long 10cm diameter 200 μm solid fibers conduit being made by polypropylene material, the a diameter of 250 μm local bulkiness of conduit head end spherical, damages Schlemm tube wall tissue when preventing from intubating.
Animal pattern extremity bondage is lain on the back in operating-table, art eye routine disinfection drape, put eye speculum, dilution iodophor solution rinses conjunctival sac, take after locally moistening anesthesia under 0.4ml 2% lignocaine Rhizoma Atractylodis Macrocephalae eye conjunctiva, do superior rectus traction sutures to fix, by timepiece dial telegoniometer, in 11 positions to 1 position edge ring bulbar conjunctiva incision, centered by 12 positions, place makees the shallow-layer scleral flap of 1/3 scleral thickness of the size about 4*4mm with limbus of corneae as substrate, a size about 3*3mm, the Deep Layer of Sclera lobe of thickness about 2/3 scleral thickness is done again below shallow-layer scleral flap.And peel off to cornea direction, find Schlemm to manage and cut Schlemm pipe outer wall, in Schlemm pipe two ends, injecting polymer hyaluronic acid (Healon GV) with 30G syringe needle, enable the duct to easily by opening.In 9 or 3 o ' clock orientation limbus of corneae at 1.0 mm, flat iris direction row paracentesis of anterior chamber, light pressure puncture orifice trailing edge, releases appropriate aqueous humor and reduces intraocular pressure, and anterior chamber is reduced pressure and microtubular is inserted after puncturing the broken ends of fractured bone of Schlemm pipe, difference according to required target intraocular pressure, detour 360 degree or 270 degree or 180 degree or 90 degree along Schlemm pipe respectively, cut off conduit, be placed in Schlemm blocking Schlemm pipe, stop ah outflow, cause the model that its intraocular pressure raises.Finally with 10-0 polypropylene line tight suture scleral flap 4-6 pin, paracentesis of anterior chamber mouth injection balance saline solution is observed, and sews up with the non-leakage watertight that is considered as, then with 10-0 polypropylene suturing with thread management conjunctival flap 2 pin.The postoperative anti-inflammatory drug that gives, monitors intraocular pressure, prosthomere response situation.
The present invention places material by operation and blocks its aqueous humor flow pass, intraocular pressure is caused to raise the glaucoma animal model of optic nerve lesion, the chronic intraocular hypertension animal model produced by this method, its intraocular pressure can regulate and control according to the scope difference of blocking Schlemm.And the fiber duct of different specification size can be selected according to different animals kind Schlemm caliber, complete Schlemm blockage, thus produce the ocular hypertension model of many animals type..The fiber duct specification that lagophthalmos, the animal model of monkey eye use can use long 10cm diameter 200 μm, and conduit head end spherical diameter is 250 μm, the optional conduit specification matched with its Schlemm caliber of other animals.In chronic intraocular hypertension glaucoma Mechanism Study, preferably build the modeling animal agreed with mutually with clinic and modeling method, provide basis for carrying out chronic glaucoma optic nerve injury mechanism.
The above is only the preferred embodiment of the present invention, and protection scope of the present invention is not limited merely to above-described embodiment, and all technical schemes belonged under thinking of the present invention belong to protection scope of the present invention.It should be pointed out that, for those skilled in the art, some improvements and modifications without departing from the principles of the present invention, these improvements and modifications also should be regarded as protection scope of the present invention.

Claims (7)

1. the method for building up of a chronic intraocular hypertension animal model, it is characterised in that comprise the following steps: animal pattern bondage is lain on the back by (1), art eye sterile drape, puts eye speculum, rinses conjunctival sac, under art eye conjunctiva after the anesthesia of local profit, do superior rectus traction sutures and fix;
(2) timepiece dial telegoniometer is pressed, in 11 positions to 1 position edge ring bulbar conjunctiva incision, centered by 12 positions, place makees the shallow-layer scleral flap of 1/3 scleral thickness of size 4*4mm with limbus of corneae as substrate, size 3*3mm is done again below shallow-layer scleral flap, the Deep Layer of Sclera lobe of thickness 2/3 scleral thickness, and peel off to cornea direction, find Schlemm to manage and cut Schlemm pipe outer wall;
(3) in Schlemm pipe two ends, polymer hyaluronic acid is injected, fiber duct conduit is passed through opening, in 9 or 3 o ' clock orientation limbus of corneae at 1.0 mm, flat iris direction row paracentesis of anterior chamber, light pressure puncture orifice trailing edge, release water and reduce intraocular pressure, anterior chamber is reduced pressure and fiber duct is inserted after puncturing the broken ends of fractured bone of Schlemm pipe, 360 degree or 270 degree or 180 degree or 90 degree are detoured along Schlemm pipe, cut off conduit, it is placed in Schlemm blocking Schlemm pipe, stop ah outflow, sew up scleral flap, , paracentesis of anterior chamber mouth injection balance saline solution, sew up conjunctival flap, give anti-inflammatory drug, finally set up the animal model that intraocular pressure raises.
The method for building up of a kind of chronic intraocular hypertension animal model the most according to claim 1, it is characterised in that use dilution iodophor solution to rinse conjunctival sac in described step (1).
The method for building up of a kind of chronic intraocular hypertension animal model the most according to claim 1, it is characterised in that use the lignocaine of 0.4ml 2% to carry out profit anesthesia in local under art eye conjunctiva in described step (1).
The method for building up of a kind of chronic intraocular hypertension animal model the most according to claim 1, it is characterised in that use 30G syringe needle to inject polymer hyaluronic acid in Schlemm pipe two ends in described step (1).
The method for building up of a kind of chronic intraocular hypertension animal model the most according to claim 1, it is characterised in that in described step (3), fiber duct includes a cylindrical solid conduit, described tube at one end is spherical structure.
The method for building up of a kind of chronic intraocular hypertension animal model the most according to claim 5, it is characterised in that the long 10cm of described fiber duct, diameter 200 μm, the spherical diameter of described tube at one end is 250 μm.
The method for building up of a kind of chronic intraocular hypertension animal model the most according to claim 5, it is characterised in that described fiber duct uses polypropylene material to make.
CN201610249471.5A 2016-04-21 2016-04-21 Establishment method for chronic high intraocular pressure animal model Pending CN105943186A (en)

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CN201610249471.5A CN105943186A (en) 2016-04-21 2016-04-21 Establishment method for chronic high intraocular pressure animal model
PCT/CN2017/078965 WO2017181835A1 (en) 2016-04-21 2017-03-31 Method for establishing chronic ocular hypertension animal model
JP2018532502A JP6505325B2 (en) 2016-04-21 2017-03-31 Method of producing chronic high intraocular pressure non-human animal model

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WO2017181835A1 (en) * 2016-04-21 2017-10-26 温州眼视光发展有限公司 Method for establishing chronic ocular hypertension animal model
CN107981969A (en) * 2017-12-29 2018-05-04 温州医科大学附属眼视光医院 Drainage substitutes biomimetic scaffolds in a kind of glaucoma
CN109481071A (en) * 2019-01-16 2019-03-19 沈阳眼产业技术研究院有限公司 A kind of method for building up of chronic intraocular hypertension animal model
CN109907857A (en) * 2019-02-28 2019-06-21 中国人民解放军第四军医大学 A device for injecting polyester fiber microspheres in front of mouse eyeball
CN111053626A (en) * 2019-12-26 2020-04-24 中国人民解放军总医院 Molding method, animal model and application thereof
CN113133431A (en) * 2021-02-25 2021-07-20 中南大学 Establishment method, model and application of chronic ocular hypertension combined long-axis animal model
CN113273546A (en) * 2021-02-25 2021-08-20 中南大学 Application of lauromacrogol in preparation of chronic ocular hypertension animal model and animal model

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CN111110441A (en) * 2020-01-08 2020-05-08 孙河 An experimental rat episcleral vein injection device and method

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Publication number Priority date Publication date Assignee Title
WO2017181835A1 (en) * 2016-04-21 2017-10-26 温州眼视光发展有限公司 Method for establishing chronic ocular hypertension animal model
CN107981969A (en) * 2017-12-29 2018-05-04 温州医科大学附属眼视光医院 Drainage substitutes biomimetic scaffolds in a kind of glaucoma
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CN109481071A (en) * 2019-01-16 2019-03-19 沈阳眼产业技术研究院有限公司 A kind of method for building up of chronic intraocular hypertension animal model
CN109907857A (en) * 2019-02-28 2019-06-21 中国人民解放军第四军医大学 A device for injecting polyester fiber microspheres in front of mouse eyeball
CN109907857B (en) * 2019-02-28 2023-10-31 中国人民解放军第四军医大学 A device for injecting polyester fiber microspheres into the front of mouse eyeballs
CN111053626A (en) * 2019-12-26 2020-04-24 中国人民解放军总医院 Molding method, animal model and application thereof
CN111053626B (en) * 2019-12-26 2021-08-20 中国人民解放军总医院 A kind of modeling method and animal model and its application
CN113133431A (en) * 2021-02-25 2021-07-20 中南大学 Establishment method, model and application of chronic ocular hypertension combined long-axis animal model
CN113273546A (en) * 2021-02-25 2021-08-20 中南大学 Application of lauromacrogol in preparation of chronic ocular hypertension animal model and animal model

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JP6505325B2 (en) 2019-04-24
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Application publication date: 20160921