Abstract: Objective To investigate the relationship between the morphology, size, and quantity of pigment particles in aqueous outflow channel and intraocular pressure (IOP) in a DBA/2J mouse model of pigmentary glaucoma. Design Experimental study. Participants Twenty male DBA/2J mice (40 eyes) aged 9 weeks. Method IOP and anterior segment were monitored regularly. Three mice (6 eyes) were randomly selected at 12, 20, 28 and 36 weeks of age and divided into normal IOP group and high IOP group due to the IOP level. The microstructure of aqueous outflow channel and the distribution of pigment particles between two groups were observed under light microscope. The morphology of pigment particles in the anterior chamber (AC) and trabecular meshwork (TM) was examined by transmission electron microscope, and the diameters of 100 pigment particles were randomly measured by ImageJ software. The diameters of pigment particles in the TM were compared between two groups. Main Outcome Measures IOP, diameter of pigment particles in the AC and TM. Results Progressive pigment liberation, iris stromal atrophy and transillumination defects were found in DBA/2J mice from 20 weeks of age. IOP of DBA/2J mice did not increase at the age of 12 and 20 weeks, and 36.4% and 75% of mice had an increased IOP at 28 and 36 weeks of age, respectively. IOP of mice at different weeks of age was statistically significantly (X２=37.82, P<0.001). Compared with the normal IOP group, the iris in the high IOP group was thinner, with accumulation of pigment-overloaded cells in the AC and on the anterior and posterior iris surfaces, narrowing of anterior chamber angle, and a large amountof pigment particles deposition in TM. The pigment granules in the AC of DBA/2J mice were round in shape with an average diameter of (0.44±0.12 um), or were oval with an average length of (0.77±0.20 um). The diameter of 58.6% round pigment particles and the length of 63.3% oval pigment particles were distributed in 0.40~0.80 um. In normal IOP group, the diameter of 53.3% round pigment particles and the length of 100% oval pigment particles in the TM were >0.40 um. In high IOP group, the diameter of 100% round pigment particles and the length of 100% oval pigment particles length in the TM were >0.40 um. The diameter of round pigment particles (0.58±0.11 um) and the length of oval pigment particles (0.90±0.12 um) in the TM of DBA/2J mice in high IOP group were both greater than those in normal IOP group (0.42±0.12 um, 0.72±0.12 um), and the difference was statistically significant (t=-6.82, -4.657; P<0.001). Conclusion In DBA/2J mice, the maximum permeable diameter in aqueous outflow channel is 0.40 μm. Pigment granules bigger than 0.40 um play the most important role in causing aqueous outflow obstruction and IOP elevation. (Ophthalmol CHN, 2022, 31: 33-38)

Key words: DBA/2J mice, intraocular pressure, pigment particles, pigmentary glaucoma, pathogenesis