动物造模,药效评价,低眼压青光眼 z-bio 2024-08-01 487

　　Low intraocular pressure can cause damage to eye tissue. Long term low intraocular pressure can cause papilledema, retinal hemorrhage, exudation, and radial wrinkles in the macula. The optic disc is a part of the central nervous system, not peripheral nerve tissue. Just like brain tissue is sensitive to hypoxia and ischemia, prolonged low intraocular pressure can cause nutritional and metabolic disorders in the optic nerve, leading to pathological changes.

　　The main causes of low intraocular pressure in clinical practice are eye trauma, eye surgery, intraocular inflammation, etc. Temporary low intraocular pressure may be caused by local vascular and neurological dysfunction, or by damage to capillary endothelium and ciliary epithelium, resulting in reduced aqueous humor production. Long term persistent low intraocular pressure can be caused by detachment of the ciliary body, resulting in obstruction between the anterior chamber and the upper ciliary body, forming an aqueous humor bypass.

　　[Modeling Method] Rabbit, weighing 1.5-3.0kg, with normal intraocular pressure in both eyes. One eye of the experimental rabbit will be used as the experimental eye, and the other eye will be used as the control eye. Anesthetize the ear vein with a 25% Uratan solution, administer 0.5% lidocaine eye drops to the experimental eye for ocular surface anesthesia, then remove the 2.0mm × 3.0mm deep sclera, perform ciliary body thermocoagulation, and perform a major iridectomy at 12 o'clock. Postoperative anti-inflammatory treatment, observation and recording of eye conditions, and measurement of intraocular pressure. Rabbit eyes with intraocular pressure consistently below 1.3kPa (10mmHg) are considered successful in modeling.

　　[Model Features]

　　1. The ultrastructure of the optic disc in normal control eyes is mainly composed of a large number of myelinated nerve fibers and a small number of glial cells. The outer layer of myelinated nerve fibers shows neatly arranged lamellar myelin sheaths, and a large number of microfilaments and microtubules can be seen in the axons.

　　2. Experimental study on the ultrastructure of the optic disc: ① After 7 days of low intraocular pressure, most of the optic nerve fiber structures were basically normal, with a small amount of myelinated nerve fibers showing mild vacuoles, and normal glial cells. ② When the intraocular pressure is low for 10 days, most of the nerve fiber axons show mild vacuoles, a small amount of nerve fibers are normal, and glial cells are normal At 14 days of low intraocular pressure, there was significant vacuolization in the axons of nerve fibers, with some myelin sheaths dispersing between layers. Mitochondria in astrocytes showed mild vacuolization (mild pathological changes) At 21 days of low intraocular pressure, there is severe vacuolization in the axons of nerve fibers, dissolution of microfilaments and microtubules, aggravated separation of myelin sheaths, partial rupture of some nerve fibers, vacuolization of mitochondria in astrocytes, and widening of the perinuclear space (significant pathological changes) At 30 days of low intraocular pressure, there is extreme vacuolization of nerve fiber axons, dissolution of microfilaments and microtubules, rupture and fragmentation of myelin sheath layer structure, swelling of astrocytes and oligodendrocytes, extreme vacuolization of mitochondria, rupture of cell membranes, and significant widening of perinuclear spaces (severe irreversible pathological changes).

　　This method is simple and easy to implement for model evaluation and application. In addition, laser-induced and alpha chymotrypsin can also induce a low intraocular pressure model of glaucoma in rabbits. The following drugs can also be used to create low intraocular pressure: after using 0.15% Timonolol eye drops, intraocular pressure significantly decreases and is related to the physiological cycle of intraocular pressure; 2% docetamide causes a significant decrease in intraocular pressure, and also has a good effect on reducing intraocular pressure at night; 1% adrenaline causes a long-term decrease in intraocular pressure, but the side effects are significant, leading to increased eye closure and blinking. This model is suitable for studying the occurrence, development, and treatment outcomes of low intraocular pressure diseases.