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Min Zhao, Wankun Xie, Wencong Chen, Travis W Hein, Lih Kuo, Robert H Rosa; Intravitreal stanniocalcin-2 reduces photoreceptor degeneration and improves oscillatory potentials with elevated ocular blood flow in retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4876. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Changes in ERG oscillatory potentials (OP) have been identified as sensitive predictors of alterations in the retinal microcirculation before ophthalmoscopic pathology. The relationship between the changes in OP and ocular blood flow (OBF) in association with retinal structural changes in retinal degenerative diseases remains unclear. Herein, we used the rhodopsin transgenic (P23H-1) rat to address these issues and to determine whether stanniocalcin-2 (STC-2) affects these retinal parameters.
Hemizygous P23H-1 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, blood flow velocities (BFV) in the central retinal artery (CRA), posterior ciliary artery, ophthalmic artery and carotid artery were measured by Doppler ultrasound. OP1-OP4 were recorded. Retinal morphology was examined by SD-OCT. The correlation between ERG OP, retinal morphology, and OBF was evaluated.
Retinal ONL thickness and OP amplitudes in the scotopic ERG were decreased in BSS treated P23H-1 vs. WT-SD eyes. The same parameters were significantly increased in STC-2 treated P23H-1 eyes, especially ONL thickness and OP1 amplitudes. The BFV (normalized to carotid artery) were not different between WT-SD and BSS-treated P23H-1 rats. However, BFV were significantly increased only in the CRA in both P23H-1 and WT-SD rats treated with STC-2. Moreover, the increase in BFV in the CRA correlated with the increase of OP1, OP2, OP3, and OP4 amplitudes in the P23H-1 rats and only OP1 in the WT-SD rats. Stepwise multiple regression analysis demonstrated that CRA velocity was an independent factor associated with OP1 and OP4 in the P23H-1 rats.
ONL thickness is significantly reduced in P23H-1 rats without obvious changes in ocular blood flow velocity in the early phase of degeneration. STC-2 rescues photoreceptor morphology/function and increases CRA BFV, which correlates with increased OP1 and OP4 amplitudes in the P23H-1 rat. It appears that STC-2 reduces retinal degeneration and enhances OP, possibly in part by increasing CRA blood flow.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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