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Linnea T Taylor, Hodan Abdshill, Jesper Bergwik, Bo Åkerström, Fredrik K Ghosh; Alpha-1-microglobulin attenuates oxidative stress and enhances photoreceptor survival in an in vitro model of rhegmatogenous retinal detachment. Invest. Ophthalmol. Vis. Sci. 2018;59(9):993.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To explore early cell and oxidative stress reactions, ultrastructural alterations, and the effect of Alpha-1-microglobulin (A1M) treatment in an in vitro model of rhegmatogenous retinal detachment (RRD).
Methods: A previously described method of simulating RRD was used with adult retinal porcine explants kept free-floating in culture medium, with or without A1M supplementation. Explants were examined at 5 time points from 1-24 hours using transmission electron microscopy as well as quantitative real-time PCR (RT-PCR) to quantify gene expression of the cell and oxidative stress markers heat shock protein 70 (Hsp70) and heme oxygenase (HO-1). In addition, the cell damage marker lactate dehydrogenase (LDH) and oxidative stress DNA damage marker 8-Oxo-2’-deoxyguanosine (8-OHdG) at each time point was examined in the culture medium.
Results: Progressive ultrastructural morphological changes were seen in untreated free-floating retinal explants from 1 hour in culture and onwards including dissolution of the retinal architecture, marked loss of photoreceptor perikarya, shortened outer segments, and mitochondria inner structure disruption in inner segments, especially in the rods. Similar, but less severe, alterations were present in A1M-treated retinas. After 24 hours, these specimens displayed viable photoreceptors with attenuated cone and rod inner segment mitochondrial damage.Tissue levels of Hsp70 (p<0.001) and LDH (p<0.001), as well as 8-OHdG (p<0.05) in the culture medium were significantly lower in A1M-treated explants compared with untreated counterparts at 24 hours of culture whereas the reverse relationship was true for HO-1 (p<0.001).
Conclusion: Photoreceptors in retinal explants devoid of tissue support, simulating a detached retina floating in the vitreous, rapidly display degenerative changes including extensive damage to mitochondriae indicating loss of energy transduction as an early key pathological event. Rod inner segment mitochondria are particularly affected, but evidence of limited damage in cones is also present early. Dissolution of the retinal structure and mitochondrial disruption can be significantly attenuated by the radical scavenger A1M, highlighting the importance of oxidative stress in the progression of cellular damage suggesting an avenue of future clinical treatment.
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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