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Min Zhao, Wankun Xie, Shu-Huai Tsai, Maxwell G. Su, Travis W Hein, Lih Kuo, Robert H Rosa; Stanniocalcin-2 preserves retinal function in a rat model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2018;59(9):997. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is a blinding inherited disease characterized by progressive photoreceptor degeneration. Mutations in the rhodopsin gene account for up to 40% of all cases of autosomal dominant (AD) RP. Currently, there is no effective therapy for RP. Recent studies demonstrated the protective effect of stanniocalcin-2 (STC-2), an endogenous multifunctional protein, on neuronal damage. However, it is unclear whether STC-2 protects the retina from degeneration. Herein, we used the P23H rhodopsin transgenic rat, a model of the most common form of ADRP in the U.S., to investigate whether STC-2 rescues or delays retinal degeneration.
Heterozygous P23H rats and age-matched wild type Sprague Dawley (WT-SD) rats received intravitreal injections of STC-2 (5 μl, 0.5 μg/μL) in the right eye at postnatal day 11 (P11) and P15. The left eye received balanced salt solution (BSS, 5 μl) as a control. At P42, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed to evaluate the retinal function and morphology, respectively. Retinal histology was evaluated by H&E staining of paraffin-embedded sections.
The thickness of both the inner nuclear (INL) and outer nuclear layers (ONL) in BSS treated P23H rat eyes decreased by 50% at P42 compared to BSS treated WT-SD eyes, as measured by SD-OCT and light microscopy. In contrast, the INL and ONL thickness decreased by only 35% in the STC-2 treated P23H rat eyes. In P23H rat eyes, the number of retinal ganglion cell nuclei per 200 μm unit length of retina was increased by 40% in the STC-2 treated eyes compared to the BSS treated fellow eyes. The mean a-wave, b-wave, and oscillatory potential (OP) amplitudes in the scotopic ERG decreased by about 70%, 40%, and 50%, respectively, in the BSS treated P23H rat eyes; whereas, the same ERG amplitudes were only reduced by 63%, 25%, and 30%, respectively, in the P23H rat eyes treated with STC-2. STC-2 had no apparent effects on retinal morphology in the WT-SD eyes.
Intravitreal administration of STC-2 rescues or delays retinal degeneration, both morphology and function, in the P23H rhodopsin transgenic rat. STC-2 seemingly promoted survival of retinal cells in the ganglion cell, inner nuclear, and outer nuclear layers. The results suggest that STC-2 might be a promising therapy for inherited retinal degenerations.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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