Characterization of Retinal Degeneration in a RHO^P23H/+ Mouse Model of Retinitis Pigmentosa

Abstract

Purpose : To investigate the progression of retinal degeneration in the RHO^P23H/+ knock-in mouse model of retinitis pigmentosa.

Methods : Longitudinally monitoring of retinas from RHO^P23H/+ knock-in mice and wild-type (WT) mice were performed postnatally at P28, P35, P41, and P69 using a commercial spectral-domain optical coherence tomography (SD-OCT) (Bioptigen Inc). The images were centered at the optic nerve head, spanning from temporal to nasal and covering a 1.6 mm field of view. Each horizontal B-scan consisted of 640 A-lines and was averaged across five repeats for better image quality. Segmentations of retinal layers were initially delineated using automated software and then manually corrected by three independent graders. The optic nerve head was manually labeled and excluded from analysis. The remaining image area was divided into eight subregions, each spanning 160 microns laterally. In addition to the layers of photoreceptor cells, thicknesses of slabs in retina circuitry across the entire retinal depth including the inner retina and retinal pigment epithelium (RPE) were also measured. Two-sampled t-tests were used to determine the significance (p < 0.05) of the retinal damages of RHO^P23H/+ knock-in mice in the corresponding regions.

Results : Twelve eyes from RHO^P23H/+ mice and six eyes from (WT) type mice were included in this study. Retinal degeneration in the outer nuclear layer (ONL) and the inner and outer segments (IS/OS) were confirmed at P28 in all eight subregions and observed to continue progressing throughout the following time points (Fig. 1), with consistently thicker ONL and IS/OS layers in the nasal subregions than their temporal subregions. RPE thickness was successfully quantified and demonstrated thinning at P41 and P69, but not at P28 and P35. Concurrently, the inner nuclear layer (INL) and the outer plexiform layer (OPL) were observed to be affected as early as P41 but not for the ganglion cell complex (GCC) including the nerve fiber layer (NFL) and the inner plexiform layer (IPL) located at the innermost of the retina. The progression of retinal degeneration was more evident by normalizing the retinal layer thicknesses to that of the (GCC).

Conclusions : This temporal-spatial quantification of OCT imaging unravels the morphological changes of inner retina and RPE cells along with photoreceptor degeneration. The ganglion cells remain unaffected during the monitoring period.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.