In vivo Investigation of Lens Opacifications in an Alzheimer’s Disease Mouse Model by OCT

Abstract

Purpose : To evaluate OCT as a tool for in vivo investigations of the crystalline lens in a mouse model of Alzheimer’s disease and analyze the morphology of cataractous lesions in 3D.

Methods : The crystalline lenses of 8 wildtype (Wt) and 8 transgenic (Tg) APP-PS1 mice between 17 and 24 months old were investigated. A custom-made OCT system (Fig. 1 A) operating at 1310 nm wavelength, providing an axial resolution 4.8 µm in tissue and a sensitivity of 100 dB, was used for imaging the mice in vivo. The mice were anesthetized with a mixture of ketamine and xylazine diluted in phosphate-buffered saline solution. Artificial tear drops were used to keep the eyes moist. Histological sections were prepared post mortem. The OCT datasets were anonymized and independently graded by three experts between 0 (no opacification) and 3 (severe opacification). The intensity of the opacities was quantified using the Weber contrast (WC) and compared between the Wt and Tg groups as well as between adult (17/18 months) and old (23/24 months) mice.

Results : OCT enabled the visualization of opacities with distinctly different shapes and sizes (Fig. 1 B-E). Hyperscattering opacifications were observed in both Wt and Tg mice. From a total of 30 eyes, 15 showed opacities in the lens (6 Wt, 9Tg) (Fig. 1 F-G). A bubble-shaped lesion (Fig. 2 A) was observed in 4 Wt and 2 Tg mouse eyes. In the corresponding histological sections, similarly structured lesions were observed in the anterior lens, matching the location in the OCT data (Fig. 2 B). An exemplary 3D visualization of an opacity is shown in the volumetric OCT reconstruction in Fig. 2 C. The lesion scores for Wt and Tg determined by the three readers (Fig. 2 D) revealed distinct distributions, yet no statistically significant difference (p = 0.061). A significant difference (p = 0.242) was found neither between the WC measured for Wt and Tg (Fig. 2 E) nor between the adult and old mice groups (p = 0.206), albeit a tendency towards higher WC was observed in older mice (Fig. 2 F).

Conclusions : OCT visualizes lesions in the crystalline lens in vivo and provides volumetric information on opacifications. While no significant differences were observed between lesions in Wt and Tg mice in the animal model investigated here, our image data suggest that OCT might be a powerful tool for quantitative imaging in preclinical studies of cataractous lesions in rodent models.

This is a 2020 ARVO Annual Meeting abstract.