Stanniocalcin-1 enhances ellipsoid zone intensity and cone function in the P23H rhodopsin transgenic pig

Abstract

Purpose : Acquired and inherited retinal degenerations have been shown to alter the integrity of the ellipsoid zone and reduce cone photoreceptor function. We previously reported the beneficial effect of intravitreal administration of stanniocalcin-1 (STC-1) on retinal structure and function in P23H rhodopsin transgenic (TgP23H) pigs exhibiting rapid photoreceptor degeneration. Herein, we examined the influence of STC-1 on ellipsoid zone intensity and cone function in the TgP23H pig.

Methods : TgP23H and wild type (WT) hybrid pig littermates were obtained from the National Swine Resource and Research Center. Intravitreal STC-1 (50 μL, 0.5 μg/μL) was administered in one eye every 2 weeks from postnatal day 15 (P15) to P75. The fellow eye was injected with balanced salt solution (BSS, 50 μL) as a control. Retinal morphology was evaluated by SD-OCT in vivo. The relative intensity of the ellipsoid zone (EZ) was determined as a ratio of the intensity of the EZ zone to the external limiting membrane (ELM) at 3000 μm from optic nerve head in the superior retina. Histologic analysis was performed using epoxy resin embedded sections at P90. ERG was performed to evaluate the retinal function in vivo at P90.

Results : Compared to the WT pig, the relative EZ intensity decreased by 68.6% in BSS treated TgP23H pig eyes. The relative EZ intensity increased by 90.8% in STC-1 treated eyes compared to BSS treated eyes in the TgP23H pig as measured by SD-OCT. The photoreceptor cell nuclear count increased by 57.7% in STC-1 treated eyes compared to BSS treated eyes in the TgP23H pig. The mean photopic a-wave, b-wave and 30Hz b-wave amplitudes at a stimulus intensity of 3.0 cd●s●m^-2 were decreased by 70.8%, 64.5% and 71.3%, respectively, in the BSS treated TgP23H pig compared with a reduction of 42.7%, 43.4% and 49.1%, respectively, in the TgP23H pig treated with STC-1.

Conclusions : Intravitreal administration of STC-1 appears to improve EZ integrity, reduce retinal degeneration, and enhance cone photoreceptor function in a porcine model of the most common form of autosomal dominant retinitis pigmentosa in the United States. In accordance with other reports in experimental models and human disease, quantitative measurements of the relative EZ intensity using SD-OCT can be employed for longitudinal assessment of retinal photoreceptor degeneration.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.