녹내장성 마우스 모델 DBA/2J의 비정상적 안구 형태변화와 실험모델로써의 적합성

Abstract

Glaucoma is a degenerative disease of the optic nerve associated with abnormal intraocular pressure, linked to the abnormal production and outflow of aqueous humor circulating within the eye. If the amount generated becomes abnormally excessive or if the drainage angle is blocked, leading to a significant increase in intraocular pressure, degeneration occurs in the retinal layers and the optic nerve. Particularly, damage is known to occur in the layer of nerve cells. Globally, it has an incidence rate of approximately 3.54% between the ages of 40 and 60. Prior to conducting experiments on glaucoma, we aimed to perform a phenotype analysis of DBA/2J, which serves as the experimental group. Previously reported characteristics in this strain include iris atrophy and depigmentation, closure of the anterior chamber angle, abnormally increased intraocular pressure (IOP) speculated to be due to these changes, and subsequent degeneration of glaucomatous retinal layers, all occurring between 3 and 6 months of age. DBA/2N from the same lineage was used as the control group, and observations were made from 1 to 15 months of age. Various observations were conducted to confirm the expression of these phenomena. These included observations of iris atrophy and depigmentation through anterior segment photography, intraocular pressure measurement using a tonometer, observations of the anterior chamber angle and retinal layers using optical coherence tomography (OCT) and electroretinography (ERG), and observations of changes in retinal inner layer thickness using H&E histological staining. The results of the experiments showed clear changes in anterior segment photography. In DBA/2J, changes in the iris began to appear after 3 months, with abnormal thickening of the outer edge of the iris or gradual disappearance of changes in pupil size. Additionally, changes due to depigmentation, speculated to be caused by inflammation, led to interference in subsequent observations. Intraocular pressure data obtained from individuals exhibiting such changes also showed a clear difference from the control group (IOP mean in both eyes at 15 months: DBA/2N approximately 12.3 mmHg, DBA/2J 17.3 mmHg). OCT data confirming the closure of the anterior chamber angle performed later also showed clearer results in the experimental group. However, other tests performed did not reveal significant differences. ERG showed no significant differences in the values of both a-wave and b-wave between the experimental and control groups (at 12 months, a-wave - DBA/2J: -56.9 ± 32.8, DBA/2N: -56.9 ± 6.3 / b-wave - DBA/2J: 91.7 ± 37.7, DBA/2N: 94.7 ± 30.4). While some changes were observed in the overall thickness of the retina with age, changes in the inner retinal layers were not clearly visible. Age-related changes were not distinct in the results of H&E histological staining. In conclusion, the expression of glaucomatous symptoms in DBA/2J appeared to be somewhat consistent. These symptoms included iris atrophy, depigmentation, and closure of the anterior chamber angle, resulting in an increase in IOP. However, as previously reported, results regarding degeneration, such as changes in the thickness of the ganglion cell layer in the inner retina, did not show significant differences. Additionally, issues affecting the experiments were observed in the changes in the anterior segment, such as blockage of the pupil due to depigmentation. Particularly, changes in the cornea occurred near the center of the eye, leading to conditions such as the formation of blood vessels, resulting in obstruction of the pupil and interference in IOP measurements. Some individuals with blocked pupils made observations through devices such as OCT and ERG impossible. Therefore, additional research is deemed necessary for the study of glaucomatous diseases in DBA/2J.