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Marisol del Valle Cano, Roma Pegany, Joshua Ocasio, Audrey Collins, Sayantan Datta, Lei Wang, tongyun Liu, Sonny Dike, James T Handa; Visual Cycle Proteins Increase Acutely After Stimulation with CSE. Invest. Ophthalmol. Vis. Sci. 2018;59(9):342. doi: https://doi.org/.
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Oxidative stress has been described to contribute to Age-Related Macular Degeneration (AMD), but its role in early vision loss is undefined. Likewise, inflammation, whether complement or non-complement derived, has emerged as a potential cause of AMD, but how inflammation affects vision has been understudied. Polymorphisms in complement factor H (CFH), and decreased Pentraxin 3 (PTX3), a major innate immunity component that regulates CFH abundance, have been associated with AMD. STAT3 is a transcription factor involved in cell survival that can be activated by either inflammation or oxidative stress, and can affect Rpe65 production. The following study evaluates the combined effect of oxidative stress and complement dysregulation on STAT3 mediated visual protein expression in an acute setting.
2 month old WT and PTX3KO mice received intravitreal injection of Cigarette Smoke Extract (CSE 250mg/ml) and were sacrificed 24h post injection. Pure RPE protein was extracted and expression of STAT3, pSTAT3, and the visual cycle proteins RPE65, LRAT, RLBP1 and RBP1 were evaluated by western blot.
After Intravitreal CSE injection, WT mice had increased pSTAT3 (p≤0.001), RPE65 (p≤0.004), LRAT (p≤0.04), and RLBP1 (p≤0.04) while RBP1 was unchanged compared to vehicle control. When compared to WT mice, PTX3KO mice had higher basal levels of pSTAT3 (p≤0.03), RPE65 (p≤0.0005), LRAT (p≤0.04), and RLBP1 (p≤0.03). Injection of CSE in PTX3KO mice did not further increase expression of these proteins
Acute stimulation of WT mice with Intravitreal CSE (24h) increases pSTAT3 and visual cycle proteins. Under non-stressed conditions, PTX3KO mice have higher basal levels of pSTAT3, RPE65, LRAT and RLBP1 compared to WT mice. These data suggest that acutely oxidative stress and low-grade inflammation stimulate the visual cycle. Whether this observation persists over time remains to be determined.
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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