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Tapasi Rana, Marina S Gorbatyuk; TNFα-deficiency mitigates the retinal degeneration in T17MRHO . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5404.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that several inflammatory events such as the TNFα, NFkB, IL-1β, IL-6 and MCP-1 elevation, accompanied by microglia activation (F4/80 and Iba1), are involved in the photoreceptor degeneration of T17M rhodopsin (RHO) mice mimicking the human autosomal dominant retinitis pigmentosa (ADRP). These results have suggested that the TNF-α pathway plays an important role in the pathogenesis of ADRP retinas and the impact of TNFα in the ADRP ocular pathology has to be verified. Therefore, we investigated the role of TNF-α and TNFa-activated cellular signaling in the retinal pathogenesis of T17MRHO mice.
T17MRHO, TNF+/-, T17MRHO TNF+/- and C57BL6 mice were involved in the study. ERG and OCT were performed for all groups at P30, P60 and P90.
Analysis of the scotopic ERG recording demonstrated that the a-wave amplitudes in the T17M RHO TNFα+/- mice were significantly increased by 429%, 229%, 217% at P30, P60 and P90, respectively when compared to T17MRHO littermates. At P30, no difference between the T17M RHO TNFα and the C57BL6 animals were recorded. Interestingly, that the b-wave ERG amplitudes were more prominently preserved in the T17M RHO TNFα. Significant elevation of the b-wave amplitudes by 234%, 157% and 131%, respectively at P30, P60 and P90 were detected in the T17MRHO TNFα+/- animals that was compatible with the amplitudes registered in the wild type retinas at P30 and P60. The SD-OCT analysis supported the ERG data and demonstrated that the average ONL thickness of the superior and inferior retinas measured within 400 nm from the optic nerve head (ONH) was significantly by 151% enhanced in the T17MRHO TNFα+/- mice at P30 as compared to ADRP control.
This study demonstrates that the TNFα-deficiency mitigates the retinal degeneration in T17M RHO mice and that the TNFα may be a promising therapeutic target to prevent loss of ADRP photoreceptor function and cell death.
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