动物造模,药效评价,白内障 z-bio 2024-08-07 608

　　1. Macaques are higher animals belonging to the primate order, and their eye anatomy and physiology are very similar to those of humans. The normal crystalline lens of macaques is also colorless and transparent, with a biconvex lens shape and a protrusion at the back compared to the front. Macaques are closely related to humans in terms of biological evolution, anatomical structure, and physiological functions. The experimental results obtained from them are relatively easy to generalize to humans, making them the most ideal experimental animals. Qi Mingxin et al. studied the incidence of spontaneous cataracts in 102 macaques (aged 4-20 years, 34 males, 64 females, 204 eyes). Observe the opacity of the crystalline lens through a slit lamp microscope. The classification and grading standard for lens opacity adopts the LOCS III lens opacity classification system. The results showed that there were 51 kinds of cataract in 204 eyes, and the incidence rate was 25%. Among them, the incidence rate of the 0-5-year-old group was 8%, the incidence rate of the 6-10-year-old group was 11%, the incidence rate of the 11-15-year-old group was 59.38%, and the incidence rate of the 16-20-year-old group was 77.27%. It can be seen that the incidence rate increases with age, and the onset age is mainly over 10 years old. From the perspective of cataract type, degree, and morphological characteristics, there are significant differences between those over 10 years old and those under 10 years old. Under the age of 10, the main type of cataract is simple (cortical or subcapsular) cataract (86.66%), while mixed cataract accounts for only 13.34%; The turbidity level is mostly below 4.0; Cloudy morphology is more common in the form of dots and patches. The types of cataracts over 10 years old are mainly mixed (58.33%), and the degree of opacity is significantly aggravated. The most common forms of opacity are radial, chrysanthemum shaped, and feather shaped. It is believed that cataract in rhesus monkeys over 10 years old shows age-related morbidity characteristics in terms of incidence rate, type, degree and morphological characteristics of cataract, and is an age-related cataract. Macaques at the age of 10 correspond to humans at 40-50 years old. Humans begin to develop age-related cataracts at 40-50 years old, and macaques also experience corresponding age-related changes from the age of 10. The incidence pattern of cataracts in macaques over 10 years old is very similar to that of age-related cataracts in humans. The final conclusion is that cataracts in macaques aged 10 and above can serve as an ideal natural animal model for human age-related cataracts.

　　2.As early as 1920, since Lezenius reported a case of naphthalene cataract in humans, naphthalene cataract has always been one of the most important animal models for cataracts due to its easy induction of cataracts. The oxidation products of naphthalene intake, β - naphthoquinone, are pathogenic substances for cataracts. Due to the presence of phenoloxidase (tyrosinase) in iris pigment cells, which can synthesize melanin, iris pigment plays a major role in the oxidation reaction of naphthalene. Someone divided the rabbits into two groups, with two brown and one gray silk haired rabbits and one New Zealand white rabbit selected for both the experimental and control groups. The weight of each rabbit is approximately 3.3kg. Dissolve naphthalene in heated liquid paraffin (10g naphthalene dissolved in 100ml paraffin). After general anesthesia, the medication is administered through a gastric tube at a dose of 1g/kg (body weight). Topiramine eye drops and epinephrine eye drops dilate the pupils, 1/d. Inspect and photograph using a slit lamp microscope and ophthalmoscope. As a result, on the first day after medication, small bubbles were visible under the capsule around the posterior crossing line of the pigmented rabbit lens, and striped opacities appeared under the anterior capsule near the equator. On the second day, small diffuse opacities appeared in the posterior sutures. On the 6th day, the turbidity under the posterior capsule worsened, and vacuoles and stripes merged into a dense posterior shell. After 2 days, the anterior subcapsular opacity also worsened. At 11 days, a large liquefaction gap extends from the subcapsule of the lens to the nucleus, causing the entire lens to expand. The formation process of cataracts in New Zealand white rabbits is similar to that of pigmented silk rabbits, but the development is relatively slow, and the earliest signs of cataracts appear after 2 weeks. The dilation period of cataracts occurs after 12 weeks. Histological examination of two pigmented rabbit eyes revealed vacuolar changes and pathological mitosis in the lens epithelium beneath the anterior capsule, swelling of some fiber cells, and formation of vacuoles beneath the posterior capsule. They concluded that after taking naphthalene for 1 day, pigment rabbits showed vacuoles, widened posterior crossing lines, increased vacuoles, and turbidity under the anterior capsule. Two weeks after medication, a large water gap appeared and extended from the subcapsular cortex to the nucleus, reaching the peak of the dilation phase of cataracts. The formation of naphthalene induced cataracts and the location of subcapsular opacities are morphologically similar to those caused by different metabolic diseases in human subcapsular cataracts. The difference is that vacuoles first appear under the posterior capsule, and the posterior crossing line appears cloudy. This type of naphthalene cataract can quickly form lens opacity under the capsule, and it can also occur in elderly people. Senile subcapsular cataract is the fastest type of senile cataract, and human senile cataract vacuoles first appear under the posterior capsule. They believe that this cataract model can serve as a model for human senile subcapsular cataract.

　　3. After studying Emory mice, Kuck et al. found that cataracts in Emory mice have a typical cataract development process. For Emory mice with a family history of cataracts, obvious lens opacity is likely to occur at 6-8 months, and many macroscopic and microscopic features are similar to age-related cataracts. This model can be used as an animal model for age-related cataracts, and has many ideal characteristics, such as slow cataract development, which can be used for early cataract research, as well as to evaluate the effects of drugs or other pathogenic factors on cataracts. Hosokawa et al. conducted a study on SAM-R/3 mice and found that in the fourth generation of this mouse strain, cataracts were evident at 10 weeks of age and worsened with age. At 20 weeks, the incidence rate of cataract in male rats is 50%~60%, while the incidence rate of cataract in female rats will continue to increase, reaching more than 90% at the end of life. After 32 weeks, 81% (52/64) female mice and 49% (23/47) male mice had at least one eye cataract, and the incidence rate of both eyes was high. Lens opacity mainly occurs in the posterior pole, characterized by protrusion of the posterior pole and dislocation of the lens nucleus. Based on the results of histology and biochemical indicators, it is believed that the onset of cataracts in SAM-R/3 mice is relatively late and age-related. They ultimately concluded that the SAM-R/3 mouse cataract model is a useful animal model for studying histological and biochemical changes in age-related cataracts.

　　4. Kolosova et al. selected 1122 (male and female) OXYS rats (55-68 generations) and used Wistar rats of the same age as controls for slit lamp microscopy examination. Select 11 OXYS rats and 11 Wistar rats, aged 10 months and 14 months, for light and electron microscopy examination. The results showed that the age of lens opacity in OXYS rats was significantly lower than that in Wistar rats. The formation of cataracts in OXYS rats is not related to gender, but to the age of the animal (F (10.897)=9.6, P=0.001). At 6 months, in the 55-56 generation of OXYS rats, 30% -40% of the lenses appeared cloudy. From generation 61 to 68 of OXYS rats, 100% showed lens opacity. These changes in the 65-68 generation crystalline lens can be detected as early as 2 months, and by 4 months, 86% (41% of both eyes) of OXYs rats can detect changes in the crystalline lens; At this age, less than 5% of Wistar rats developed cataracts, and there was not a single case of bilateral cataracts. At the age of 12 months, the bilateral lenses of OXYS rats are usually affected, while the incidence rate of cataract in Wistar rats is only 20%~28%. Actually, all Wistar rats will not develop cataracts until 28 months, but some animals still have monocular onset at this time. Microscopic examination of the crystalline lens of OXYS rats revealed the formation of mainly circular, vesicular, and dendritic cataracts. Circular opacities mainly occur in the cortex and/or nucleus of the crystalline lens, while vesicular cataracts mainly occur under the anterior capsule, and dendritic cataracts mainly occur around the nucleus of the crystalline lens. Circular cataracts are the most common, with opacities ranging from the cortex to the nucleus, becoming more pronounced with age, but not always affecting all layers of the lens, making it a typical age-related cataract change. These changes can also occur in 2-3 year old Wistar rats. The light microscopy results showed that OXYS rat cataracts involve changes in all structures of the lens, including typical atrophic changes in the lens epithelium of age-related cataracts, which worsen with age. At 10 months, a semi thin section of the equatorial region epithelium of the lens showed polymorphic features, with flattened lens epithelium, depressed cell membrane, and dense subepithelial layer. Under electron microscopy, there is mainly heterogeneity in tissue structure, osmiophilicity of the lens epithelial cell matrix, and vacuolization of membrane organelles, with some epithelial cells producing secretory substances. Moreover, a deep invagination is formed between the upper and basal cell membranes, which can connect the lens epithelium, capsule, and contents. The cytoplasm of lens epithelial fibers is mainly characterized by homogeneity and compactness, which is completely consistent with human senile cataracts. They concluded that the formation of early cataracts in OXYS rats is consistent with age-related cataracts, and this OXYS rat cataract model can serve as an ideal model for studying the pathogenesis and prevention methods of age-related cataracts.